bluuebunny/crossref_metadata_2025 huggingface dataset:
Combining Ultrasonography and Endometrial Aspiration as a One-Stop Screening for Endometrial Neoplasia
Authors: Rotenberg Ohad , Doulaveris Georgios , Goldberg Gary L. , Renz Malte , Whitney Kathleen , Dar Leeann , Rotenberg Noam , Wu Haotian , Van den Bosch Thierry , Dar Pe'er
Published: October 2024

OBJECTIVE:

To assess the performance of simultaneous endometrial aspiration and sonohysterography to screen for endometrial cancer or hyperplasia in women aged 50 years or older.

METHODS:

We conducted a prospective study from February 2014 to October 2020 at the ultrasound unit of a large urban academic medical center. The study included 1,635 women aged 50 years or older referred for endometrial evaluation, with follow-up through January 2021. Participants underwent saline infusion sonohysterography combined with ultrasound-guided endometrial aspiration. The primary outcome measured was a diagnosis of endometrial cancer or hyperplasia within 1 year from screening. The diagnostic accuracy of the combined evaluation method, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), was assessed.

RESULTS:

Of 1,170 women who completed the study protocol, 82 (7.0%) had endometrial cancer and 42 (3.6%) had endometrial hyperplasia. Of all patients who developed cancer during the follow-up period, 85.5% were diagnosed within 1 year after evaluation. The application of simultaneous endometrial aspiration and sonohysterography together demonstrated a sensitivity of 99.1%, specificity of 24.9%, PPV of 11.8%, and NPV of 99.6%. Using a theoretical sequential approach, assuming an endometrial aspiration is performed only in patients determined to be high risk by sonohysterography, demonstrated a sensitivity of 93.4%, specificity of 99.9%, PPV of 99.0%, and NPV of 99.3%.

CONCLUSION:

Simultaneous endometrial aspiration and sonohysterography is an effective one-stop outpatient screening tool for detecting endometrial cancer and hyperplasia in women aged 50 years or older. With the integration of two screening modalities into a single procedure, simultaneous endometrial aspiration and sonohysterography may overcome the limitations inherent in each of the currently recommended methods individually, potentially improving patient prognosis and streamlining the diagnostic process.
Effectiveness of Platelet-rich Plasma Injection as an Adjunct Treatment to Arthroscopy for TFCC Injury: A Retrospective Cohort Study
Authors: Asiry Abdulaziz , Dabbagh Armaghan , Mortada Hatan , Merlini Lorenzo
Published: October 2024

Background:

Triangular fibrocartilage complex (TFCC) injuries can cause significant patient dysfunction. Platelet-rich plasma (PRP) has emerged as a potential adjunctive treatment for arthroscopic TFCC repair, with some studies suggesting improved outcomes. This study aims to evaluate and compare PRP as an adjunctive treatment in arthroscopic TFCC tear repair.

Methods:

This retrospective cohort study examined patients undergoing arthroscopic TFCC repair at Institut de la Main, Paris, France (December 2021–2022). Patients were split into two groups: arthroscopic repair alone (1) and repair with PRP injections (2). Physical examinations were conducted pre- and posttreatment, recording flexion, extension, and radial/ulnar deviation of the affected and contralateral wrists.

Results:

A total of 33 patients (20 men and 13 women) with a mean age of 30.55 ± 9.17 years were included. PRP injections were given to 16 patients with arthroscopic TFCC repair; 17 had repair only. No significant differences existed preoperatively between groups in wrist function or pain (P > 0.05). The Quick Disabilities of the Arm, Shoulder, and Hand (DASH) score differed significantly (P = 0.004). The non-PRP group demonstrated better postoperative upper extremity function, with a mean Quick DASH score of 7.75 ± 5.91 compared with 12.64 ± 6.79 in the PRP group. No significant difference between groups was observed in the pain visual analog scale (P > 0.05).

Conclusions:

PRP injections with TFCC repair did not improve function over repair alone. The non-PRP group showed better function (lower Quick DASH scores). Pain reduction was similar between groups. Larger trials and cost-effectiveness studies are needed to fully assess PRP’s benefits in TFCC repair.
A Concept Analysis of Yangsaeng (Nurturing Life) Using Rogers’ Evolutionary Method
Authors: Kang Youngmi , Gu Minkyung
Published: October 2024

Yangsaeng (nurturing life) is a concept, emerging alongside the interests in well-being and a prolonged life span, that exists in many East-Asian countries. The concept of Yangsaeng was originally derived from Daoism (Taoism in modern Chinese), which emphasizes the way of cultivating mind and body. This concept analysis aimed to clarify the meaning and attributes of Yangsaeng using Roger’s evolutionary method from various disciplines. By exploring its common use in the literature, a comprehensive definition of Yangsaeng nursing was developed. By modernly reinterpreting the theories and practical needs of Yangsaeng, it is possible to respond realistically to the prevention and treatment of modern people’s psychological stress and physical illnesses.
The Utility of Serologic TORCH Testing During Pregnancy for Maternal-related Versus Fetal-related Indications: A Retrospective Study
Authors: Abu Shqara Raneen , Kaufman Maya , Or Shany , Glikman Daniel , Lowenstein Lior , Frank Wolf Maya
Published: October 2024

Background:

Clear guidelines have not been established about the utility of TORCH serology testing in women for whom TORCH infection is suspected according to clinical and laboratory manifestations during pregnancy. We aimed to compare rates of TORCH infections [specifically cytomegalovirus (CMV), Toxoplasma and rubella] in women who underwent TORCH serology testing due to maternal- versus fetal-related indications.

Methods:

This 10-year single-center retrospective study included all the women beyond 24 weeks of gestation who underwent TORCH serology testing due to maternal- or fetal-related indications. Maternal-related indications included fever, gastroenteritis, elevated liver enzymes and thrombocytopenia. Fetal-related indications included intrauterine growth restriction, polyhydramnios and oligohydramnios.

Results:

During the study period, 304 women underwent TORCH serology testing due to maternal-related indications and 771 due to fetal-related indications. For the maternal-related compared with the fetal-related indication group, maternal and congenital TORCH infections were more prevalent (P = 0.015), specifically CMV (P = 0.036). Eight (2.6%) of the women with maternal-related indications had a primary TORCH infection; 4 of them (50%) had concomitant congenital infections. Six (0.8%) of the women with fetal-related indications had a primary infection; none had a related congenital infection. Among the women with maternal-related indications, higher rates of maternal TORCH infection were found among those with thrombocytopenia (7.1%) and elevated liver enzymes (3.0%). During the study period, maternal-indicated TORCH testing detected 10.8% of neonates born with a confirmed TORCH infection.

Conclusions:

The clinical yield of TORCH serology for nonspecific sonographic fetal features was low. Nonetheless, maternal-related indications should prompt testing for CMV and Toxoplasma infection.
Clozapine-Associated Sialorrhea
Authors: Gürcan Gamze , Atalay Berk , Deveci Ece
Published: October 2024

Background

Clozapine has demonstrated efficacy in treating treatment-resistant schizophrenia; however, it has a wide range of side effects. Sialorrhea is a common side effect of clozapine that causes the patient to withdraw from social life. This review aims to evaluate and summarize the prevalence, mechanism, risk factors, and management of clozapine-associated sialorrhea.

Procedures

The literature was explored for the prevalence, the mechanisms, the risk factors, and the management of sialorrhea. The following search strings and terms were used: “clozapine,” “sialorrhea,” “hypersalivation,” “clozapine induced sialorrhea,” and “clozapine induced hypersalivation”.

Study Results

Hypersalivation is one of the most common side effects of clozapine. Over the course of clozapine therapy, hypersalivation has been reported to have an incidence of 30% to –80%. Although different treatment approaches are applied on a case-by-case basis in the clinic, depending on the practitioners' preferences, there is a lack of clear guidelines for managing this common side effect that jeopardizes patients' social life.

Conclusions

It is important for healthcare professionals and patients that some clear treatment options for clozapine-associated sialorrhea are brought to the forefront and widely used, especially based on the research conducted to date.
How illness perception congruence between patients with cancer and caregivers affects their anxiety and depression levels
Authors: Salduz Mehmet , Suiçmez Tuğba Uyar , Uncu Doğan
Published: October 2024

Background:

This study aimed to investigate the similarities or discrepancies in illness perception between patients with cancer and their primary caregivers by examining the predictive effect of illness congruence on anxiety and depression in both patients and caregivers.

Methods:

A total of 106 patients with cancer with outpatient chemotherapy aged 18–65 years (M = 49.60; SD = 11.35; 60.4% female) and 106 caregivers aged 18–65 years (M = 42.97; SD = 12.51; 50.9% female) participated in the study, which was conducted at the outpatient chemotherapy unit of a large public hospital. Data were collected through convenience sampling using a cross-sectional design. Depression and anxiety levels were measured using the Hospital Anxiety and Depression Scale, whereas illness perception was measured using the Brief Illness Perception Scale.

Results:

Multiple hierarchical regression analysis determined that higher illness perception congruence significantly predicted higher anxiety levels in patients with cancer after controlling for demographic variables.

Conclusion:

The results revealed that higher illness perception congruence between patients and their caregivers was associated with increased anxiety in patients with cancer. Both patients and caregivers perceiving the illness negatively might have accounted for the higher anxiety levels of the patients. Furthermore, the findings demonstrate and emphasize the vital role of further dyadic investigations, in which family members are also involved.
Toward a public outreach and community engagement strategy on cancer in Newfoundland and Labrador: an initial road map and recommendations
Authors: Savas Sevtap , King John , King Krista , Etchegary Holly , Whitten Cindy , Wiseman Jason , Peddle Darrell , Bishop Derrick
Published: October 2024

Background:

The province of Newfoundland and Labrador has one of the highest incidence and mortality rates for cancer among the Canadian provinces. Sharing accessible knowledge on cancer is an important part of cancer control and population health efforts. However, bringing useful health information and knowledge exchange events to residents requires an efficient and accessible system.

Objectives:

We aimed to create a road map and recommendations for effective public outreach and community engagement on cancer in Newfoundland and Labrador.

Methods:

We used the following information, experience, or public engagement tools to gather information to inform our work: discussions with the members of the Public Interest Group on Cancer Research, researchers' experiences with recruitment and knowledge translation activities, feedback provided to 2 public conferences delivered (Public Conference on Genetics delivered in 2020 and Public Conference on Cancer delivered in 2022—where the target audience was general public), and 2 public town halls (one in-person, one virtual) and 2 individual consultation sessions with key stakeholders. Information gathered was then summarized.

Results:

We identified a rich set of cancer-related topics for which to organize public events on cancer. In addition, a large number of public outreach and engagement options were identified, emphasizing the fragmented, inefficient, and resource-intensive nature of public outreach and community engagement efforts in the province. Based on the information collected, we developed an initial road map and recommendations to inform future public engagement activities and strategies. In addition, our group has started to implement the road map for our current and future public engagement activities.

Conclusions:

We present key cancer-related topics that are of public interest and issues and opportunities for recruitment and delivery of knowledge and events to residents of Newfoundland and Labrador. This information can be useful for researchers, organizations, and the health care system in the province. However, more inclusive consultations, larger collaborations, funding, and systematic data collection are needed to build a province-wide public outreach network on cancer and to identify more comprehensive public engagement options. The work presented here can potentially guide these efforts. Our work is also expected to inspire other provinces, states, and communities to assess their public outreach status and help develop road maps co-led by patients to progress their public engagement efforts in cancer.
Mesenchymal Tumors of the Skin: A Review
Authors: Drews-Elger Katherine , Williams Erik A.
Published: October 2024

Mesenchymal tumors of the skin are rare and clinically heterogeneous, and can represent diagnostic challenge for pathologists. Most of these lesions have overlapping clinical and histological features, thus the understanding of architectural patterns, cytoplasmic and stromal features can facilitate proper diagnosis. Anatomic site may be an important factor in the differential diagnosis, as are patient’s age and sex. Ancillary tests are often required and can be useful to rule out other entities. Molecular diagnostics is playing an increasingly important role in the diagnosis of soft tissue neoplasms. Here, we review clinical, histological, and molecular features of some of the most common of these uncommon entities including benign and malignant lesions.
Development, Evaluation, and Initial Findings of New York State Department of Health Community Drug Checking Pilot Programs
Authors: Payne Emily R. , Thomas Guy J. , Fallico Matthew , Clear Allan , Gogia Maka , Zamboni Lucila
Published: October 2024

Context:

The illicit drug landscape in the United States is dynamic, featuring a risky and erratic drug supply. Drug checking programs (DCP) have been successfully implemented and studied extensively in Canada and Europe but are scarce in the United States. Integrating DCP at harm reduction programs provides an opportunity to engage people at the point-of-care and deliver a combination of harm reduction services, access to healthcare services, and linkages to treatment.

Program:

The New York State Department of Health (NYSDOH) developed and supports operation of 8 pilot community DCP sites throughout the state. The DCP were trained to utilize Fourier-transform infrared spectroscopy (FTIR) technology to deliver real-time results to participants.

Implementation:

The NYSDOH community DCP pilot began development in 2022. Partnerships were formed across multiple domains including other DCP, universities, forensic laboratories, syringe service and harm reduction programs, and legal and regulatory offices within the NYSDOH. The first pilot sites began operating in mid-2023 and program expansion is on-going.

Evaluation:

Evaluation staff were extensively engaged in development and implementation phases. Qualitative evaluation focused on barriers, facilitators, and lessons learned from program staff and technicians. Quantitative evidence was gathered to assess the reach of the DCP and accuracy of results attained by drug checking technicians during their training periods. Drug checking results helped characterize the illicit drug supply.

Discussion:

Development and implementation of DCP in NYS was facilitated by strong partnerships across sectors including public health and harm reduction. DCP may involve diverse partners who do not regularly collaborate, and health departments are positioned to build relationships and convene partners for program implementation. Evaluation findings highlight the importance of facilitating on-going training and technical assistance to DCP for quality assurance. The initial successes and lessons learned from the NYSDOH DCP demonstrate state public health departments’ ability to successfully deploy this innovative harm reduction strategy.
Breast Metastasis From Sigmoid Adenocarcinoma Revealed by FDG PET/CT
Authors: Liu Yanlin , Dai Hongyuan , Su Minggang , Huang Rui
Published: October 2024

Breast metastasis from sigmoid carcinoma is rare. A 32-year-old woman, who had a history of sigmoid carcinoma, was found a hypermetabolic soft tissue mass in the left breast and a lymph node with moderate uptake on FDG PET/CT. Final pathology supported that the breast mass and lymph node were both metastases from the sigmoid carcinoma.
FDG PET/CT in a Case of Esophageal Schwannoma
Authors: Zhang Jun , Ji Xia , Dong Aisheng
Published: October 2024

Esophageal schwannoma is very rare. We describe FDG PET/CT findings in a case of benign esophageal schwannoma. Endoscopic ultrasound showed the tumor was located in the muscular layer of the esophagus. FDG PET/CT showed intense FDG uptake with SUVmax of 10 of the tumor mimicking malignancy. This case indicates that schwannoma should be included in the differential diagnosis of esophageal FDG-avid lesions.
Mildly Increased 68Ga-Pentixafor Uptake in Hepatic Hemangioma
Authors: Yang Lixiang , Huang Mingxing , Tian Rong , Li Qianrui
Published: October 2024

68Ga-pentixafor uptake in hemangioma is rare. We report 68Ga-pentixafor PET/MRI findings of a hepatic hemangioma in a 54-year-old woman. The images revealed a hyperintense lesion in the right posterior liver on T2-weighted images, with mild pentixafor uptake. The lesion was consistent with typical presentations of a hemangioma on MRI and contrast-enhanced CT.
Perinephric Extramedullary Disease in Multiple Myeloma
Authors: Koichi Alex , Zemianschi Razvan , Manzil Fathima Fijula Palot , Eichhorn Joshua
Published: October 2024

Extramedullary disease represents an aggressive form of multiple myeloma occurring outside the skeleton and is a poor prognostic indicator. Extramedullary disease most commonly involves the skin, muscle, pleura, lymph nodes, liver, and central nervous system. Infrequently, extramedullary disease can involve the kidneys or perirenal space. We present 3 cases of perirenal involvement of extramedullary disease on 18F-FDG PET/CT confirmed with tissue sampling as plasma cell infiltration. Within the limitation of physiologic activity in the kidneys due to 18F-FDG excretion, close consideration is essential when evaluating multiple myeloma patients for genitourinary involvement as it can resemble other malignancies, hemorrhage, or renal injury.
FDG Uptake in Brown Adipose Tissue Activated by a Long-Acting β2-Adrenergic Receptor Agonist Inhaler Prescribed for Bronchial Asthma
Authors: Nitta Akira , Kotani Tomoya , Okuyama Chio
Published: October 2024

We herein report a case of an elderly woman in whom brown adipose tissue (BAT) was visible on 18F-FDG PET imaging performed in the summer. In this patient, none of the well-known factors that induce BAT activation in adults, including cold exposure, catecholamine-producing tumors, or β3-adrenergic receptor agonists administration, were present. Daily inhalation of a long-acting β2-adrenergic agonist for treatment of her bronchial asthma was considered the cause of her BAT visualization. This case suggests the need to consider β2-adrenergic receptor agonists as a cause of BAT visualization.
Residual Ultrasound-Enhancing Agents Mimicking Portal Venous Gas
Authors: Bitar Ryan , Langdon Jonathan , Kaur Manroop , Crandall Ian , McNamara Robert , Revzin Margarita
Published: October 2024

Sonographic detection of mobile echogenic foci within the main portal vein and its branches or within the liver parenchyma extending along the portal triads to the periphery of the liver is an alarming finding that has been associated with portal venous gas in the setting of bowel ischemia. Ultrasound-enhancing agents (UEAs) have been widely utilized in abdominal ultrasound for evaluation of organ neoplasms and vascular patency as well as in echocardiography for the evaluation of cardiac function. The appearance of UEAs on abdominal ultrasound can resemble gas like that seen in the portal venous system and liver in patients with bowel ischemia; therefore, UEA residuals should always be a part of the differential diagnosis of echogenic foci when seen on abdominal ultrasounds with preceding recent UEA administration. In this observational study, we present a series of cases with suspected portal venous gas suspicious for bowel ischemia that turned out to be a result of residual or persistent UEA from the recent contrast-enhanced echocardiography. Discussion of this phenomenon and its potential explanation is provided.
Injectable Janus Base Nanomatrix (JBNm) in Maintaining Long-Term Homeostasis of Regenerated Cartilage for Tissue Chip Applications
Authors: Yau Anne , Sands Ian , Zhang Wuxia , Chen Yupeng
Published: October 2024

Engineered cartilage tissues have wide applications in in vivo cartilage repair as well as in vitro models, such as cartilage-on-a-chip or cartilage tissue chips. Currently, most cartilage tissue engineering approaches focus on promoting chondrogenesis of stem cells to produce regenerated cartilage. However, this regenerated cartilage can dedifferentiate into fibrotic tissue or further differentiate into hypertrophic or calcified cartilage. One of the most challenging objectives in cartilage tissue engineering is to maintain long-term cartilage homeostasis. Since the microenvironment of engineered cartilage tissue is crucial for stem cell adhesion, proliferation, differentiation, and function, we aim to develop a novel scaffold that can maintain the long-term homeostasis of regenerated cartilage. Therefore, we developed a library of Janus base nanomatrices (JBNms), composed of DNA-inspired Janus nanotubes (JBNts) as well as cartilage extracellular matrix (ECM) proteins. The JBNms were developed to selectively promote chondro-lineage cell functions while inhibiting bone and endothelial cell growth. More importantly, the JBNm can effectively promote chondrogenesis while inhibiting hypertrophy, osteogenesis, angiogenesis, and dedifferentiation. Additionally, the JBNm is injectable, forming a solid scaffold suitable for producing and maintaining regenerated cartilage tissue in microfluidic chips, making it ideal for tissue chip applications. In this study, we successfully created cartilage tissue chips using JBNms. These chips can model cartilage tissue even after long-term culture and can also mimic arthritis progression, making them useful for drug screening. Thus, we have developed a novel nanomaterial approach for improved cartilage tissue engineering and cartilage tissue chip applications.
Arabidopsis 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) synthases of the shikimate pathway display both manganese- and cobalt-dependent activities
Authors: Yokoyama Ryo , Maeda Hiroshi A
Published: October 2024

The plant shikimate pathway directs a significant portion of photosynthetically assimilated carbon into the downstream biosynthetic pathways of aromatic amino acids (AAA) and aromatic natural products. 3-Deoxy-D-arabino-heptulosonate 7-phosphate synthase (DHS) catalyzes the first step of the shikimate pathway, playing a critical role in controlling the carbon flux from central carbon metabolism into the AAA biosynthesis. Previous biochemical studies suggested the presence of manganese- and cobalt-dependent DHS enzymes (DHS-Mn and DHS-Co, respectively) in various plant species. Unlike well-studied DHS-Mn, however, the identity of DHS-Co is still unknown. Here, we show that all three DHS isoforms ofArabidopsis thalianaexhibit both DHS-Mn and DHS-Co activitiesin vitro. A phylogenetic analysis of various DHS orthologs and related sequences showed that Arabidopsis 3-deoxy-D-manno-octulosonate-8-phosphate synthase (KDOPS) proteins were closely related to microbial Type I DHSs. Despite their sequence similarity, these Arabidopsis KDOPS proteins showed no DHS activity. Meanwhile, optimization of the DHS assay conditions led to the successful detection of DHS-Co activity from Arabidopsis DHS recombinant proteins. Compared to DHS-Mn, DHS-Co activity displayed the same redox dependency but distinct optimal pH and cofactor sensitivity. Our work provides biochemical evidence that the DHS isoforms of Arabidopsis possess DHS-Co activity.
Unique belowground ecological strategies of subtropical and tropical plant species expand the root trait space
Authors: Guerrero-Ramírez Nathaly R. , Weemstra Monique , Addo-Danso Shalom D. , Andersen Kelly , Arnaud Marie , Cordeiro Amanda L. , Cusack Daniela F. , Kotowska Martyna M. , Lee Ming Yang , Leroy Céline , Lugli Laynara F. , Pierick Kerstin , Smith-Martin Chris M. , Toro Laura , Umaña María Natalia , Valverde-Barrantes Oscar J , Wong Michelle , Fortunel Claire
Published: October 2024

Root trait variation may reflect the ecological and evolutionary processes shaping biodiversity, but remains poorly quantified in the (sub)tropics. Here, we aim to further complete our knowledge of belowground functional strategies by assessing the contributions of subtropical and tropical species to global root trait diversity. We gathered root data for 1618 temperate, 341 subtropical, and 775 tropical species. We compared functional diversity among biomes and calculated the unique contribution of each biome to the global root economics space. Further, we determined if the within-variation of subtropical and tropical biomes is shaped by species’ niches and/or differences in evolutionary history. Root trait expressions differed among biomes, but root functional diversity did not. Furthermore, subtropical and tropical biomes accounted for 40% of the unique root functional space within the global traits space. Species’ climate niches and phylogenetic turnover explained variation in root traits (e.g., denser root tissue was associated with drier sites) among subtropical but not tropical species. Through their unique root traits, sub(tropical) species strongly expand the current ‘global’ root trait space. This work underwrites their importance in conceptual models for more complete insights into how various belowground strategies drive plant functional biogeography and biodiversity globally.
Assessing the Alignment of Biomedical Research and Clinical Translation
Authors: Sun Mengyi , Stoeger Thomas , Nunes Amaral Luís A
Published: October 2024

More than half of all drug clinical trials fail due to lack of efficacy, highlighting gaps in our understanding of disease-target relationships. While it is widely believed that scientific research is essential for identifying drug-targets, whether scientists can allocate their research attention according to the clinical potential of disease-target relationships is unknown. To answer this question, we analyzed data from Open Targets, a comprehensive disease-target relationship platform. By building an open pipeline that follows drugs through consecutive clinical trial phases, we demonstrate that research attention in the disease-specific primary literature can predict trial success. However, research attention toward specific targets are not predictive for overall trial success across diseases. Our study thus highlights the crucial, yet complex, role of the primary research literature in steering clinical trials, encouraging a more nuanced approach to translational medicine.
James-Stein estimator improves accuracy and sample efficiency in human kinematic and metabolic data
Authors: Alwan Aya , Srinivasan Manoj
Published: October 2024

Human biomechanical data are often accompanied with measurement noise and behavioral variability. Errors due to such noise and variability are usually exaggerated by fewer trials or shorter trial durations, and could be reduced using more trials or longer trial durations. Speeding up such data collection by lowering number of trials or trial duration, while improving the accuracy of statistical estimates, would be of particular interest in wearable robotics applications and when the human population studied is vulnerable (e.g., the elderly). Here, we propose the use of the James-Stein estimator (JSE) to improve statistical estimates with a given amount of data, or reduce the amount of data needed for a given accuracy. The JSE is a shrinkage estimator that produces a uniform reduction in the summed squared errors when compared to the more familiar maximum likelihood estimator (MLE), simple averages, or other least squares regressions. When data from multiple human participants are available, an individual participant’s JSE can improve upon MLE by incorporating information from all participants, improving overall estimation accuracy on average. Here, we apply the JSE to multiple time-series of kinematic and metabolic data from the following parameter estimation problems: foot placement control during level walking, energy expenditure during circle walking, and energy expenditure during resting. We show that the resulting estimates improve accuracy — that is, the James-Stein estimates have lower summed squared error from the ‘true’ value compared to more conventional estimates.
Species-specific loss of genetic diversity and exposure of deleterious mutations following agricultural intensification
Authors: Nolen Zachary J. , Jamelska Patrycja , Lara Ana Sofia Torres , Wahlberg Niklas , Runemark Anna
Published: October 2024

Agriculture driven land-use change is a major contributor to insect declines globally. As a result of population decline and subdivision, species lose genetic diversity, potentially reducing adaptive potential and increasing genetic load, reinforcing decline. We examine how genetic diversity has changed over the past century in three Polyommatinae butterfly species in Sweden, leveraging genome sequencing of specimens from museum collections. Based on 63 historical and 92 contemporary genomes, we document a general decline in genetic diversity and reveal that the extent of decline depends on habitat specialization. The habitat generalist has retained most of its genetic diversity and connectivity. In contrast, the two specialists have declined sufficiently that even common variation is being eroded by drift, with up to a 3.3% reduction in heterozygosity per decade in the strongly grassland associatedCyaniris semiargus. While this sharp decline has reduced the burden of strongly deleterious mutations in the specialist species, increased population isolation has led to inbreeding inCy. semiargus, exposing a greater proportion of weakly deleterious mutations in homozygous state. This realized burden likely reduces mean fitness and reinforces population decline, highlighting the need for well-connected grassland landscapes to maintain grassland specialist functional connectivity and genetic diversity. We complement these analyses with seven additional Polyommatinae species, uncovering that declines are common across the group, with alarming rates of genetic decline in species listed as viable. This study highlights the urgency of incorporating genetic data into conservation planning, as threats from genetic erosion are not captured by current conservation assessment.
Thalamic Roles in Conscious Perception Revealed by Low-Intensity Focused Ultrasound Neuromodulation
Authors: Jang Hyunwoo , Fotiadis Panagiotis , Mashour George A. , Hudetz Anthony G , Huang Zirui
Published: October 2024

The neural basis of conscious perception remains incompletely understood. While cortical mechanisms of conscious content have been extensively investigated, the role of subcortical structures, including the thalamus, remains less explored. We aim to elucidate the causal contributions of different thalamic regions to conscious perception using transcranial low-intensity focused ultrasound (LIFU) neuromodulation. We hypothesize that modulating different thalamic regions would result in distinct perceptual outcomes. We apply LIFU in human volunteers to investigate region-specific and sonication parameter-dependent effects. We target anterior (transmodal-dominant) and posterior (unimodal-dominant) thalamic regions, further divided into ventral and dorsal regions, while participants perform a near-threshold visual perception task. Task performance is evaluated using Signal Detection Theory metrics. We find that the high duty cycle stimulation of the ventral anterior thalamus enhanced object recognition sensitivity. We also observe a general (i.e., region-independent) effect of LIFU on decision bias (i.e., a tendency toward a particular response) and object categorization accuracy. Specifically, high duty cycle stimulation decreases categorization accuracy, whereas low duty cycle shifts decision bias towards a more conservative stance. In conclusion, our results provide causal insight into the functional organization of the thalamus in shaping human visual experience and highlight the unique role of the transmodal-dominant ventral anterior thalamus.
RELEASE: REdressing Long-tErm Antidepressant uSE in adults in general practice (RELEASE): A two-arm parallel-group cluster RCT effectiveness-implementation hybrid type-1 study
Authors:   a pragmatic multicentre, superiority, parallel group, controlled study of participants allocated to a multi-strategy intervention vs Usual Care, Wallis Katharine , Donald Maria , Horowitz Mark , Ware Rob , Byrnes Joshua , Moncrieff Joanna , Zwar Nicholas , Scott Ian , Morgan Mark , Freeman Christopher , Gill Neeraj , Sturman Nancy , Geraghty Adam , Partanen Riitta , Lynch Johanna
Published: October 2024

The REdressing Long-tErm Antidepressant uSE in general practice (RELEASE) trial is a pragmatic cluster randomized controlled trial (cRCT) that seeks to determine whether a novel multi-strategy intervention that supports safe cessation of long-term antidepressants is superior to Usual Care.1Pragmatic trials are designed to determine how well interventions work in clinical practice under everyday conditions.2

The multi-strategy intervention has two forms, known as RELEASE and RELEASE+. RELEASE for patients includes direct patient education and resources3and an invitation to medication review; RELEASE for general practitioners (GPs) includes education, training in the brief intervention (Ask, Advise, Assist) and printable resources via practice management software. RELEASE+ additionally includes for patients links to freely available information online via an App, and for GPs clinical audit and feedback on practice prescribing of antidepressants. Patient directed education material has the potential to support safer prescribing, including in this case improved recognition and management of antidepressant withdrawal symptoms.4, 5Brief interventions have the potential to change GP prescribing behaviour.6The primary comparison of interest is whether any RELEASE intervention is superior to Usual Care. A secondary comparison will be between the two types of RELEASE interventions (RELEASE and RELEASE+).

The purpose of this document is to minimise bias and ensure transparency and internal validity for the findings of the trial, by defining and making publicly available the analysis approach prior to reviewing or analysing trial data. The statistical analysis plan (SAP) will inform analysis and reporting of the main effectiveness findings of the trial. It provides a detailed description of the primary and secondary trial outcomes and the methods for statistical comparison.
Alpha coherence is a network signature of cognitive recovery from disorders of consciousness
Authors: Zhou David W , Conte Mary M , Curley William H , Spencer-Salmon Camille A , Chatelle Camille , Rosenthal Eric S , Bodien Yelena G , Victor Jonathan D , Schiff Nicholas D , Brown Emery N , Edlow Brian L
Published: October 2024

Alpha (8-12 Hz) frequency band oscillations are among the most informative features in electroencephalographic (EEG) assessment of patients with disorders of consciousness (DoC). Because interareal alpha synchrony is thought to facilitate long-range communication in healthy brains, coherence measures of resting-state alpha oscillations may provide insights into a patients capacity for higher-order cognition beyond channel-wise estimates of alpha power. In multi-channel EEG, global coherence methods may be used to augment standard spectral analysis methods by both estimating the strength and identifying the structure of coherent oscillatory networks. We performed global coherence analysis in 95 separate clinical EEG recordings (28 healthy controls and 33 patients with acute or chronic DoC, 25 of whom returned for follow-up) collected between two academic medical centers. We found that posterior alpha coherence is associated with recovery of higher-level cognition. We developed a measure of network organization, based on the distance between eigenvectors of the alpha cross-spectral matrix, that detects recovery of posterior alpha networks. In patients who have emerged from a minimally conscious state, we showed that coherence-based alpha networks are reconfigured prior to restoration of alpha power to resemble those seen in healthy controls. This alpha network measure performs well in classifying recovery from DoC (AUC = 0.78) compared to common representations of functional connectivity using the weighted phase lag index (AUC = 0.50 - 0.57). Lastly, we observed that activity within these alpha networks is suppressed during positive responses to task-based EEG command-following paradigms, supporting the potential utility of this biomarker to detect covert cognition. Our findings suggest that restored alpha networks may represent a sensitive early signature of cognitive recovery in patients with DoC. Therefore, network detection methods may augment the utility of EEG assessments for DoC.
Evaluation of the Impact of a 90-day Mortality Prediction Model Integrated in the EHR for Advanced Care Planning*
Authors: Rossi Lorenzo A. , Roberts Laura , Olivares Marinel , Christian Amis , Mooney Stefanie , Morse Denise , Zachariah Finly
Published: October 2024

Medical centers have begun to integrate AI models for mortality prediction in their electronic health records (EHR) systems to support advance care planning.1There is evidence that advance care planning can reduce suffering and unwanted, costly treatment near the end of life.2

To better target patients at a risk of death with advance directive (AD) capture and goals of care (GOC) conversations at our comprehensive cancer center, we developed and integrated a 90-day mortality prediction model in the EHR. The model has been live since February, 2021. Performance in production has matched very closely pre-production pilots, achieving an 85% AUROC (AI Showcase Stage I). We implemented 4 clinical decision support (CDS) tools driven by the model to promote goal concordant care in inpatient and outpatient encounters (AI Showcase Stage II).3

In this document, we analyze the impact of one of the aforementioned CDS applications, implemented as an inter-ruptive alert for the clinical social workers (CSWs) to facilitate advance directive (AD) completion in the inpatient setting. We also present preliminary results on volumes of GOC conversations prompted by one of the model-driven alerts. Our analysis is based on 12 months of data, collected between March 1, 2021 and February 28, 2022.

The challenges for our assessment included inconsistent EHR documentation practices, coexistence with (traditional) non-AI driven processes tasked for similar goals and many external factors that can affect target outcomes. We believe such challenges to be rather common across healthcare organizations integrating AI in their workflows.
Enhanced RNA-targeting CRISPR-Cas technology in zebrafish
Authors: Moreno-Sanchez Ismael , Hernandez-Huertas Luis , Nahon-Cano Daniel , Gomez-Marin Carlos , Martinez-García Pedro Manuel , Treichel Anthony J. , Tomas-Gallardo Laura , da Silva Pescador Gabriel , Kushawah Gopal , Díaz-Moscoso Alejandro , Cano-Ruiz Alejandra , Walker John A. , Muñoz Manuel J. , Holden Kevin , Galcerán Joan , Nieto María Ángela , Bazzini Ariel , Moreno-Mateos Miguel A.
Published: October 2024

CRISPR-Cas13 systems are widely used in basic and applied sciences. However, its application has recently generated controversy due to collateral activity in mammalian cells and mouse models. Moreover, its efficiency could be improved in vivo. Here, we optimized transient formulations as ribonucleoprotein complexes or mRNA-gRNA combinations to enhance the CRISPR-RfxCas13d system in zebrafish. We i) used chemically modified gRNAs to allow more penetrant loss-of-function phenotypes, ii) improved nuclear RNA-targeting, and iii) compared different computational models and determined the most accurate to predict gRNA activity in vivo. Furthermore, we demonstrated that transient CRISPR-RfxCas13d can effectively deplete endogenous mRNAs in zebrafish embryos without inducing collateral effects, except when targeting extremely abundant and ectopic RNAs. Finally, we implemented alternative RNA-targeting CRISPR-Cas systems with reduced or absent collateral activity. Altogether, these findings contribute to CRISPR-Cas technology optimization for RNA targeting in zebrafish through transient approaches and assist in the progression of in vivo applications.
Genome-Wide Identification of Stable RNA Secondary Structures Across Multiple Organisms Using Chemical Probing Data: Insights into Short Structural Motifs and RNA-Targeting Therapeutics
Authors: Wang Jingxin
Published: October 2024

Small molecules targeting specific RNA binding sites, including stable and transient RNA structures, are emerging as effective pharmacological approaches for modulating gene expression. However, little is understood about how stable RNA secondary structures are shared across organisms, an important factor in controlling drug selectivity. In this study, I provide an analytical pipeline named RNA Secondary Structure Finder (R2S-Finder) to discover short, stable RNA structural motifs for humans,Escherichia coli(E. coli), SARS-CoV-2, and Zika virus by leveraging existing in vivo and in vitro genome-wide chemical RNA-probing datasets. I found several common features across organisms. For example, apart from the well-documented tetraloops, AU-rich tetraloops are widely present in different organisms. I also found that the 5’ untranslated region (UTR) contains a higher proportion of stable structures than the coding sequences in humans, SARS-CoV-2, and Zika virus. In general, stable structures predicted from in vitro (protein-free) and in vivo datasets are consistent in humans,E. coli, and SARS-CoV-2, indicating that most stable structure formation were driven by RNA folding alone, while a larger variation was found between in vitro and in vivo data with certain RNA types, such as human long intergenic non-coding RNAs (lincRNAs). Finally, I predicted stable three- and four-way RNA junctions that exist both in vivo and in vitro conditions, which can potentially serve as drug targets. All results of stable sequences, stem-loops, internal loops, bulges, and three- and four-way junctions have been collated in the R2S-Finder database (https://github.com/JingxinWangLab/R2S-Finder), which is coded in hyperlinked HTML pages and tabulated in CSV files.
Navigating the Privacy-Accuracy Tradeoff: Federated Survival Analysis with Binning and Differential Privacy
Authors: Gouthamchand Varsha , van Soest Johan , Arcuri Giovanni , Dekker Andre , Damiani Andrea , Wee Leonard
Published: October 2024

Federated learning (FL) offers a decentralized approach to model training, allowing for data-driven insights while safeguarding patient privacy across institutions. In the Personal Health Train (PHT) paradigm, it is local model gradients from each institution, aggregated over a sample size of its own patients that are transmitted to a central server to be globally merged, rather than transmitting the patient data itself. However, certain attacks on a PHT infrastructure may risk compromising sensitive data. This study delves into the privacy-accuracy tradeoff in federated Cox Proportional Hazards (CoxPH) models for survival analysis by assessing two Privacy-Enhancing Techniques (PETs) added on top of the PHT approach. In one, we implemented a Discretized Cox model by grouping event times into finite bins to hide individual time-to-event data points. In another, we explored Local Differential Privacy by introducing noise to local model gradients. Our results demonstrate that both strategies can effectively mitigate privacy risks without significantly compromising numerical accuracy, reflected in only small variations of hazard ratios and cumulative baseline hazard curves. Our findings highlight the potential for enhancing privacy-preserving survival analysis within a PHT implementation and suggest practical solutions for multi-institutional research while mitigating the risk of re-identification attacks.
Prevalence and patient characteristics associated with cardiovascular disease risk factor screening in UK primary care for people with severe mental illness: An electronic healthcare record study
Authors: N Launders , CA Jackson , JF Hayes , A John , R Stewart , MH Iveson , E Bramon , B Guthrie , SW Mercer , DPJ Osborn
Published: October 2024

Background

People with severe mental illness (SMI) are at increased risk of cardiovascular disease (CVD), and initiatives for CVD risk factor screening in the UK have not reduced disparities.

Objectives

To describe the annual screening prevalence for CVD risk factors in people with SMI from April 2000 to March 2018, and to identify factors associated with receiving no screening and regular screening.

Methods

We identified adults with a diagnosis of SMI (schizophrenia, bipolar disorder or ‘other psychosis’) from UK primary care records in Clinical Practice Research Datalink (CPRD). We calculated the annual prevalence of screening for blood pressure, cholesterol, glucose, body mass index, alcohol consumption and smoking status, using multinomial logistic regression to identify factors associated with receiving no screening and complete screening.

Results

Of 216,136 patients with SMI, 55% received screening for all six CVD risk factors at least once follow-up and 35% received all six within a one-month period. Changes in screening prevalence coincided with changes in incentivisation of screening. In 2014-2018, men, people with a diagnosis of ‘other psychoses’, or with missing ethnicity were more likely to have received no screening.

Conclusions

The low proportion of people with SMI receiving regular comprehensive CVD risk factor screening is concerning. Screening needs to be embedded as part of broad physical health checks to ensure the health needs of people with SMI are being met. If we are to improve cardiovascular health, interventions are needed where risk of receiving no screening or not receiving regular screening is highest.

What is already known on this topic

The prevalence of CVD risk factor screening in primary care increased with the introduction of an incentivisation scheme and when incentivisation for screening for specific CVD risk factors is removed the screening decreases.

What does this study add?

Few patients received regular screening for all six CVD risk factors considered, and both screening prevalence and risk of receiving no screening varied depending on patient characteristics.

Only 35% of patients ever received screening for all six CVD risk factors considered in a one-month period, suggesting that screening is not often being done as part of a physical health check.

How this study might affect research, practice or policy

Clinicians should be aware that some sub-groups of patients with SMI are less likely to receive screening, and the importance of providing screening as part of a regular, comprehensive physical health check.