bluuebunny/crossref_metadata_2025 huggingface dataset:
The relationship and influencing factors of critical thinking and medical ethical decision-making among pediatric medical students
Authors: Dang Hongxing , Li Shaojun , Li Jing
Published: September 2024

Pediatric diseases possess unique characteristics, requiring pediatricians to have strong critical thinking skills and sound ethical decision-making abilities. This study aims to investigate and analyze the critical thinking dispositions of pediatric medical students and their impact on ethical decision-making levels, and to propose suggestions for improving teaching methods. A cross-sectional study design was adopted, using the Chinese version of the California Critical Thinking Disposition Inventory (CCTDI-CV) and an ethical decision-making questionnaire. An online survey was conducted among 240 pediatric medical students at Chongqing Medical University, collecting participants’ basic demographic information. The study described the CCTDI-CV scores and ethical decision-making questionnaire scores (mean ± standard deviation), with distribution and trend analyses performed using t tests and H-tests. Pearson correlation analysis was used to examine the relationship between the 2, and regression analysis was conducted to explore factors influencing ethical decision-making abilities. A total of 229 students (95.4%) completed the survey. The overall average score of critical thinking disposition among pediatric medical students was 287.96 ± 39.09, with 139 students (60.70%) demonstrating positive or highly positive critical thinking dispositions. Ethical decision-making abilities were excellent in 85 students (37.12%). There was a significant positive correlation between critical thinking abilities and ethical decision-making abilities (R = 0.774, P < .001), particularly with analysis abilities, systematic abilities, and cognitive maturity showing higher correlations with total ethical decision-making scores. CCTDI-CV scores had a significant positive impact on ethical decision-making levels (P < .001), with factors such as family background and high school performance also significantly influencing ethical decision-making abilities (P < .001). Chinese pediatric medical students generally exhibit strong critical thinking and ethical decision-making abilities. Critical thinking plays a crucial role in medical ethical decision-making, with family background and high school performance being important influencing factors. Educators should focus more on developing multidimensional critical thinking skills to enhance students’ ethical decision-making abilities, thereby improving overall healthcare service quality. The study results also provide new perspectives for international pediatric medical educators.
Common Diagnostic Challenges in Genitourinary Mesenchymal Tumors: A Practical Approach
Authors: Velez Torres Jaylou M. , Kryvenko Oleksandr N.
Published: September 2024

Mesenchymal neoplasms within the genitourinary tract include a wide spectrum of tumors, ranging from benign to malignant, and tumors of uncertain malignant potential. Except for stromal tumors of the prostate, which originate from the specific prostatic stroma, these neoplasms generally resemble their counterparts in other body sites. The rarity of these neoplasms and the limitation associated with small biopsy samples present unique diagnostic challenges for pathologists. Accurate diagnosis is paramount, as it significantly influences prognosis and guides management and treatment strategies. This review addresses common diagnostic scenarios, discusses key differential diagnoses, and sheds light on potential diagnostic pitfalls.
Stratified Mucin-producing Lesions of the Anus
Authors: Sappenfield Ryan , Camacho-Cordovez Felipe , Larman Tatianna , Xing Deyin , Montgomery Elizabeth A. , Ronnett Brigitte M. , Voltaggio Lysandra
Published: September 2024

Primary anal cancers are rare and typically driven by high-risk human papillomavirus (HPV) infection. Though squamous cell carcinoma is most common, a spectrum of HPV-related nonsquamous anogenital neoplasms with similarities to cervical stratified mucin-producing carcinoma has been reported. In this study, we mined our institutional archives to characterize the clinicopathologic features of this emerging entity. Six cases were identified from the files at 2 institutions, including 4 cases of invasive stratified mucin-producing carcinoma and 2 stratified mucin-producing intraepithelial lesions (SMILE). Four patients were women, and the mean age was 70 years. Patients presented with rectal/anal mass or polyp, rectal bleeding or pain, weight loss, or at the time of screening colonoscopy. Tumors displayed histologic features as described in the gynecologic tract. Cases of invasive stratified mucinous carcinoma showed infiltrative tumor nests with variable intracytoplasmic mucin, peripheral palisading, prominent apoptosis, and neutrophilic infiltrate. One invasive stratified mucinous carcinoma associated with high grade glandular dysplasia, whereas 1 SMILE was next to conventional low-grade squamous intraepithelial lesion. All lesions stained with p16 showed block-like p16 expression. HPV in situ hybridization was performed in 5 cases, 4 of which were positive; one was interpreted as equivocal. Follow-up information, available in 4 patients, revealed 1 local recurrence followed by death due to unrelated causes in a patient with invasive stratified mucin-producing carcinoma. We report the first series of HPV-associated primary anal stratified mucin-producing neoplasms analogous to those seen in the gynecologic tract, further broadening the spectrum of HPV-related anal neoplasia.
Impact of Geopolitical Unrest on Surgical Delays and Outcomes in Immigrant Populations With Cleft Lip and Palate
Authors: Güray Şeyda , Evin Nuh , Sifil Melih K. , Yildiz Kemalettin , Güneren Ethem
Published: September 2024

Background:

Geopolitical conflicts in the Middle East have led to mass migrations, with Turkey becoming a major host country. This influx has strained the health care system, particularly regarding specialized care for conditions like cleft lip and palate (CLP). Timely intervention is crucial for optimal outcomes, but cultural, socioeconomic, and logistical barriers often cause delays, impacting physical, functional, and psychosocial development.

Methods:

This retrospective study analyzed 72 immigrant pediatric CLP patients treated in Turkey between 2012 and 2022. Data on demographics, medical history, surgical interventions, complications, and treatment delays were collected. Surgical timing was compared with American Cleft Palate Craniofacial Association guidelines, and the impact of socioeconomic status on delays was assessed.

Results:

Seventy-two patients underwent a total of 91 surgical interventions, including 29 cleft lip repairs, 22 cleft palate repairs, 6 pharyngeal flaps, 15 fistula closures, 8 corrections of secondary lip scars and whistling deformities, and 11 alveolar bone graftings. A majority (73.6%) had poor socioeconomic status. The average delays for cleft lip, cleft palate, and alveolar bone grafting surgeries were 5.3±4, 7.3±6.1, and 34.1±23.5 months, respectively, and were significantly longer for patients with poor socioeconomic status (P=0.00502, 0.030741, and 0.041878). The average delay for pharyngeal flap surgery, performed in patients with poor socioeconomic status (except for one), was 43.7±14.1 months.

Conclusions:

This study highlights the challenges and disparities in CLP care for immigrant children in Turkey due to geopolitical conflict. While surgical complication rates are similar to established data, delays in treatment, especially among those with lower socioeconomic status, are a significant concern. The findings emphasize the need for comprehensive, culturally sensitive care and systemic interventions to improve access and outcomes for this vulnerable population.
First Case Report of Disseminated Gonococcal Arthritis in Newfoundland & Labrador
Authors: Karsenti Nessika , Nelder Matthew , LeMeissurier Jennifer , Bourassa-Blanchette Samuel , Taylor Robert
Published: September 2024

Introduction: Disseminated gonococcal infections (DGIs) are a rare but often debilitating complication of N. gonorrhoeae infections. Often presenting as arthritis-dermatitis syndrome, true suppurative joint infections are an even more rare form of DGI. Here, we present the first known case of DGI in Newfoundland and Labrador in over 10 years.
Case report: A 50-year-old man who is known to inject drugs with multiple housing and social challenges presented to the emergency department with a two-day history of an isolated painful, erythematous knee. After being assessed by orthopedics and undergoing an operative debridement, intraoperative cultures grew N. gonorrhoeae. He was treated with intravenous (IV) ceftriaxone, and his course in hospital was complicated by inadequate pain control and a lack of stable housing.  
Conclusion: DGIs, while rare, need to remain on any clinician’s differential for septic arthritis given the increasing prevalence of gonorrheal infections in Canada, and in Newfoundland and Labrador. In addition, patients who are at risk of delaying accessing care, such as people who inject drugs and unhoused individuals, are at higher risk of complicated hospital stays.
Insights into the molecular basis of beet curly top resistance in sugar beet through a transcriptomic approach at the early stage of symptom development
Authors: Eini Omid , Benjes Kristin , Dietrich Katrin , Reichelt Michael , Schumann Nadine , Varrelmann Mark
Published: September 2024

Curly top disease caused by Beet curly top virus (BCTV) is a limiting factor for sugar beet production. The most economical and sustainable control of BCTV in sugar beet would be via the growth of resistant cultivars, although most commercial cultivars possess only low-to-moderate quantitative resistance. A double haploid line (KDH13) showed a high level of resistance to BCTV infection. However, the mechanism of resistance and response of this line to BCTV infection is unknown. Here, we tested the response of this line to both local and systemic BCTV infections. The virus replicated at a high level in locally infected tissue but lower than in susceptible KDH19 plants. Resistant KDH13 plants systemically infected with BCTV showed only mild enation without leaf curling after 30 days. In contrast, severe leaf curling appeared after 12 days in susceptible plants with higher virus accumulation. Transcriptome analysis of the BCTV-infected KDH13 plants at the early stage of symptom development showed only 132 genes that were exclusively deregulated compared to the regulation of a large number of genes (1018 genes) in KDH19 plants. Pathway enrichment analysis showed that differentially expressed genes were predominantly involved in hormone metabolism, DNA methylation, immune response, cell cycle, biotic stress and oxidative stress. The auxin level in both resistant and susceptible plants increased in response to BCTV infection. Remarkably, exogenous application of auxin caused leaf curling phenotype in the absence of the virus. This study demonstrates the response of resistant and susceptible plants to BCTV infection at both local and systemic infections and highlights the defence-related genes and metabolic pathways including auxin for their contribution towards BCTV symptom development and resistance in sugar beet.
An unfortunate natural experiment in learning how to provide services to those in need: The case of Ukrainian war refugees with disabilities in Warsaw and Bucharest
Authors: Nowicka Monika , Deliu Alexandra , Voicu Bogdan , Szarota Magdalena
Published: September 2024

When helping others, experience becomes important, especially in circumstances that involve interacting with a different culture—such as the ones implied in providing services to refugees. When disability is added to refuge, multiple types of experience become necessary, with the capacity for cross-sector collaboration being an asset. This paper explores the impact of the Russian invasion of Ukraine on the capacity of the Polish and Romanian organizations providing services to Ukrainian refugees in Warsaw and Bucharest, with a focus on disabled refugees. Based on 41 interviews with service providers/grass-roots organizations, it turns out that this unfortunate event served as a natural laboratory for practicing, acquiring, and increasing skills in multiple domains, leading to increased personal and institutional expertise. We inspect the differences between Warsaw and Bucharest, the first city having more experience in dealing with incoming flows of immigrants, the second being a newcomer in this respect. We also consider the distinction between public providers (public administration) and non-governmental organization entities, observing the upscaling of the latter. Implications for policy are considered within the framework of curtailing civic society under the illiberal wave.
Harmonization of Margin of Stability Calculations and Investigation of the Impact of Foot Length, Foot Width, Gait Speed, and Body Mass
Authors: Dussault-Picard Cloé , Robidou Claire , Tisserand Romain , Cherni Yosra
Published: September 2024

The margin of stability (MoS), the minimum distance between the extrapolated center of mass and the edges of the base of support (BoS), is one of the most widely used metric to describe the mechanical stability during gait. In the current literature, the markers used to define the edges of the BoS are variable and the MoS model neglects the influence of anthropometric factors, such as foot length, foot width, and body mass. This study aimed to evaluate differences between anteroposterior (AP) and mediolateral (ML) MoS measures using various BoS edge definitions (AP: n = 3 methods, ML: n = 4 methods) and to investigate the impact of foot length, foot width, gait speed, and body mass on the MoS measures. Results show that the BoS edges definition affects the resulting MoS across the entire stance phase (AP: p<0.001 between the 3 methods; ML: p<0.001 between the 4 methods). Moreover, the AP MoS is influenced by foot length (p<0.029), as well as gait speed and body mass on both the AP (gait speed: p<0.001; body mass: p<0.038) and ML (gait speed: p<0.032; body mass: p<0.001) MoS. This study proposes a new approach based on optimal foot markers for defining the edges of the BoS, which may contribute to better assess mechanical stability during gait. Finally, the results suggest that normalizing the MoS (i.e., the AP MoS by foot length, gait speed, and body mass, and the ML MoS by gait speed and body mass) can facilitate comparisons between populations.
The utility of environmental data from traditional varieties for climate-adaptive maize breeding
Authors: Li Forrest , Gates Daniel J. , Buckler Edward S. , Hufford Matthew B. , Janzen Garrett M. , Rellán-Álvarez Rubén , Rodríguez-Zapata Fausto , Navarro J. Alberto Romero , Sawers Ruairidh J. H. , Snodgrass Samantha J. , Sonder Kai , Willcox Martha C. , Hearne Sarah J. , Ross-Ibarra Jeffrey , Runcie Daniel E.
Published: September 2024

Maintaining crop yields in the face of climate change is a major challenge facing plant breeding today. Considerable genetic variation exists inex-situcollections of traditional crop varieties, but identifying adaptive loci and testing their agronomic performance in large populations in field trials is costly.

Here, we study the utility of climate and genomic data for identifying promising traditional varieties to incorporate into maize breeding programs. To do so, we use phenotypic data from more than 4,000 traditional maize varieties grown in 13 trial environments. First, we used genotype data to predict environmental characteristics of germplasm collections to identify varieties that may be locally adapted to target environments. Second, we used environmental GWAS (envGWAS) to identify genetic loci associated with historical divergence along climatic gradients, such as the putative heat shock proteinhsftf9and the large-scale adaptive inversionInv4m.

Finally, we compared the value of environmental data and envGWAS-prioritized loci to genomic data for prioritizing traditional varieties. We find that maize yield traits are best predicted by genomic data, and that envGWAS-identified variants provide little direct predictive information over patterns of population structure. We also find that adding environment-of-origin variables does not improve yield component prediction over kinship or population structure alone, but could be a useful selection proxy in the absence of sequencing data. While our results suggest little utility of environmental data for selecting traditional varieties to incorporate in breeding programs, environmental GWAS is nonetheless a potentially powerful approach to identify individual novel loci for maize improvement, especially when coupled with high density genotyping.
scooby: Modeling multi-modal genomic profiles from DNA sequence at single-cell resolution
Authors: Hingerl Johannes C. , Martens Laura D. , Karollus Alexander , Manz Trevor , Buenrostro Jason D. , Theis Fabian J. , Gagneur Julien
Published: September 2024

Understanding how regulatory DNA elements shape gene expression across individual cells is a fundamental challenge in genomics. Joint RNA-seq and epigenomic profiling provides opportunities to build unifying models of gene regulation capturing sequence determinants across steps of gene expression. However, current models, developed primarily for bulk omics data, fail to capture the cellular heterogeneity and dynamic processes revealed by single-cell multi-modal technologies. Here, we introduce scooby, the first model to predict scRNA-seq coverage and scATAC-seq insertion profiles along the genome from sequence at single-cell resolution. For this, we leverage the pre-trained multi-omics profile predictor Borzoi as a foundation model, equip it with a cell-specific decoder, and fine-tune its sequence embeddings. Specifically, we condition the decoder on the cell position in a precomputed single-cell embedding resulting in strong generalization capability. Applied to a hematopoiesis dataset, scooby recapitulates cell-specific expression levels of held-out genes and cells, and identifies regulators and their putative target genes through in silico motif deletion. Moreover, accurate variant effect prediction with scooby allows for breaking down bulk eQTL effects into single-cell effects and delineating their impact on chromatin accessibility and gene expression. We anticipate scooby to aid unraveling the complexities of gene regulation at the resolution of individual cells.
BioBrigit, A Hybrid Deep Learning and Knowledge-based Approach to Model Metal Pathways in Proteins: Application to a Di-Copper Tyrosinase
Authors: Marechal Jean-Didier , Sodupe Mariona , Sanchez Jose Emilio , Fernandez Diaz Raul , Roldan Martin Lorena
Published: September 2024

The interaction of metallic species with proteins has been fundamental in evolution and key in many physiological processes. How metals bind to proteins also holds promise in many fields, like the design of new biocatalysts or the fight against pathogens. Nonetheless, uncovering the mechanism under which proteins recruit metal ions is far from understood and is one of the challenges in bioinorganic chemistry and structural biology. Computational methods are potentially among the most promising tools for this endeavor. Only a handful of efficient structural predictors of metal binding sites exist to date. Most focus on identifying the most stable binding sites in the protein scaffolds. Although these methods are very interesting, they do not consider the exploration of transient, sub-optimal binding sites that could be relevant in metal binding pathways in proteins. At the far end of modeling capabilities nowadays, we introduce BioBrigit, a hybrid Deep Learning knowledge based approach that suggests metal binding pathways in proteins. To demonstrate the method's viability, we apply it to the di-copper tyrosinase from Streptomyces castaneoglobisporus, a system for which crystallographic experiments allowed the identification of a series of transient sites of the copper in its path from a chaperone to the final catalytic site. Combined with homology modeling and large-scale molecular dynamics, BioBrigit allows for computational characterization of all experimental sites and for better understanding of the copper recruitment mechanism. BioBrigit appears as an asset in a field full of unknowns like metal binding to proteins and opens the way to further algorithms in this area.
BTFBS: binding-prediction of bacterial transcription factors and binding sites based on deep learning
Authors: Jin Bingbing , Liang Song , Liu Xiaoqian , Zhang Rui , Zhu Yun , Chen Yuanyuan , Liu Guangjin , Yang Tao
Published: September 2024

Background

The binding of transcription factors (TFs) to TF-binding sites plays a vital role in the process of regulating gene expression and evolution. With the development of machine learning and deep learning, some successes have been achieved in predicting transcription factors and binding sites. Then a natural question arises: for a given transcription factor and a binding site, do they bind? This is the main motivation of this work.

Results

In this paper, we develop a model BTFBS, which predicts whether the bacterial transcription factors and binding sites combine or not. The model takes both the amino acid sequences of bacterial transcription factors and the nucleotide sequences of binding sites as inputs, and extracts features through convolutional neural network and MultiheadAttention.

For the model inputs, we use two negative sample sampling methods: RS and EE. On the test dataset of RS, the accuracy, sensitivity, specificity, F1-score and MCC of BTFBS are 0.91446, 0.89746, 0.93134, 0.91264 and 0.82946, respectively. And on the test dataset of EE, the accuracy, sensitivity, specificity, F1-score and MCC of BTFBS are 0.87868, 0.89354, 0.86394, 0.87996 and 0.75796, respectively. Meanwhile, our findings indicate that the optimal approach for obtaining negative samples in the context of bacterial research is to utilize the whole genome sequences of the corresponding bacteria, as opposed to the shuffling method.

Conclusions

The above results on the test dataset have shown that the proposed BTFBS model has a good performance in predicting the combination of bacterial transcription factors and their binding sites and provides an experimental guide. BTFBS is publicly available athttps://github.com/Vceternal/BTFBS.
Nocturia as a Risk Factor for Developing Frailty in Older Adults: Results of the Berlin Aging Study II
Authors: König Maximilian , Malsch Carolin , Mariño Joany , Vetter Valentin Max , Komleva Yulia , Demuth Ilja , Steinhagen-Thiessen Elisabeth
Published: September 2024

Background & Aim

The current study examined cross-sectional and longitudinal associations between nocturia and frailty in a cohort of men and women aged 60 years and older, as evidence on this topic was lacking.

Methods

Baseline and follow-up data from the Berlin Aging Study II (n=1671) assessed on average 7.1 (IQR 6.2-8.7) years apart were analyzed. Self-reported nocturia was dichotomized into </≥ 2 micturitions per night, and frailty was assessed using the Fried Frailty Phenotype. Covariables were identified a priori based on a review of the existing literature.

Results

At baseline, 70.2% of the participants were robust, 28.9% were pre-frail, and 0.9% were frail; 254 participants (23.6%) had self-reported nocturia. In longitudinal analyses, the prevalence and incidence of frailty at follow-up significantly increased when nocturia was present at baseline. Over the median follow-up of 7.1 years, there were 41 incident frailty cases (IR 5.15, 95% CI 3.79-7.00 per 1000 person-years). After adjusting for age, sex, morbidity burden, and baseline frailty status, baseline nocturia was associated with a 2.23-fold increased risk (95% CI 1.17-4.18) of frailty at follow-up.

Conclusion

Nocturia is linked to a higher risk of developing frailty in older adults, both women and men.
Diastolic dysfunction in aortic stenosis is associated with greater damping of left ventricular recoil, and not myocardial stiffness
Authors: Salman Katrin , Sundqvist Martin G , Stevenson Jonathan , Cain Peter A , Ugander Martin
Published: September 2024

Background

Aortic stenosis (AS) is associated with increasing severity of diastolic dysfunction as measured by conventional echocardiographic grading. The parameterized diastolic filling (PDF) method can describe diastolic function mechanistically, by analyzing filling using the physics of classical mechanics for spring recoil. The study aimed to use the PDF method to describe the mechanics of how diastolic dysfunction manifests in AS.

Methods

Patients (n=73) undergoing echocardiography were included according to AS of varying severity (normal/mild AS: maximum Doppler velocity across aortic valve (Vmax) <3.0 m/s, moderate/severe AS: Vmax≥3.0 m/s). PDF analysis of pulsed wave Doppler transmitral E-waves was performed using freely available software.

Results

Compared to normal/mild AS (n=41), patients with moderate/severe AS (n=32) had a left ventricle with a greater interventricular septal thickness (p=0.02) and higher E/e’ (p=0.007), but similar left ventricular ejection fraction (p=0.10) and left atrial volume index (p=0.21). PDF analysis showed that moderate/severe AS did not differ in myocardial stiffness (p=0.70), but had a higher myocardial damping (p=0.02), higher load (p=0.04), longer derived time constant of isovolumetric pressure decay (tau, p=0.004), higher filling energy (p=0.02), higher peak driving (p=0.02) and resistive (p=0.004) force of filling, lower kinematic filling efficiency index (p<0.001), but no difference in the load-independent index of diastolic function (p=0.62).

Conclusions

AS was primarily associated with a greater damping of LV recoil (increased viscoelasticity) and load, but without a change in myocardial stiffness. This provides novel insight into the mechanics of how diastolic dysfunction manifests in AS.
Characterization of Clinical MRI Findings in Moderately-Late Preterm Infants Diagnosed with Cerebral Palsy: A Single Center Retrospective Study
Authors: Fisher Elizabeth , Tartakovsky Jessica , Bliss Laura A. , Jaju Alok , Aw-Zoretic Jessie , Vernon Laura , Mithal Divakar S.
Published: September 2024

I.

Cerebral Palsy is the most common movement disorder in childhood and is commonly associated with brain injury and prematurity. At least 10% of patients have a normal brain MRI and current practices suggest genetic testing may be indicated for those patients. However, given that prematurity itself is a risk factor for CP, which MRI patterns are present in premature infants and which genetic causes are present remains unclear. In the present study, a cohort of moderate-late preterm infants born between 32 and 34 weeks gestational age was analyzed to determine whether CP disease severity, comorbid conditions, and genetic testing are associated with particular MRI findings. We identified that comorbid conditions and CP severity are similar across imaging patterns regardless of the perceived severity of the imaging findings. Genetic diagnoses were identified in 13% of all patients. In patients with MRI concerning for injuries, over 20% had genetic testing sent. Abnormal MRI findings in moderate-late preterm infants with CP are common, but are not a strong predictor of disease severity and may be associated with underlying genetic causes that are underdiagnosed due to unclear practice guidelines.
Physical therapy in patients with Parkinson’s disease treated with Deep Brain Stimulation: a Delphi panel study
Authors: Guidetti M. , Marceglia S. , Bocci T. , Duncan R. , Fasano A. , Foote K.D. , Hamani C. , Krauss J.K. , Kühn A. A. , Lena F. , Limousin P. , Lozano A.M. , Maiorana N.V. , Modugno N. , Moro E. , Okun M.S. , Oliveri S. , Santilli M. , Schnitzler A. , Temel Y. , Timmermann L. , Visser-Vandewalle V. , Volkmann J. , Priori A.
Published: September 2024

Although deep brain stimulation of the subthalamic nucleus (STN-DBS) induces motor benefits in people with Parkinson’s disease (PwPD), the size and duration of the effects of STN-DBS on motor axial (e.g., postural instability, trunk posture alterations) and gait impairments (e.g., freezing of gait – FOG) are still ambiguous. Physical therapy (PT) effectively complements pharmacological treatment to improve postural stability, gait performance, and other dopamine-resistant symptoms (e.g. festination, hesitation, axial motor dysfunctions, and FOG) in PwPD who are non-surgically treated. Despite the potential for positive adjuvant effects of PT following STN-DBS surgery, there is a paucity of science available on the topic. In such a scenario, gathering the opinion and expertise of leading investigators worldwide was pursued to study motor rehabilitation in PwPD following STN-DBS. After summarizing the few available findings through a systematic review, we identified clinical and academically experienced DBS clinicians (n=21) to discuss the challenges related to PT following STN-DBS. A 5-point Likert scale questionnaire was used and based on the results of the systematic review along with a Delphi method. Thirty-nine questions were submitted to the panel – half related to general considerations on PT following STN-DBS, half related to PT treatments. Despite the low-to-moderate quality, the few available rehabilitative studies suggested that PT could improve dynamic and static balance, gait performance and posture. Similarly, panellists strongly agreed that PT might help in improving motor symptoms and quality of life, and it may be possibly prescribed to maximize the effects of the stimulation. The experts agreed that physical therapists could be part of the multidisciplinary team taking care of the patients. Also, they agreed on prescribing of conventional PT, but not massage or manual therapy. Our results will inform the rehabilitation and the DBS community to engage, publish and deepen this area of research. Such efforts may spark guidelines for PT following STN-DBS.

GRAPHICAL ABSTRACT
Diagnostic Utility of Electrophysiological Markers for Early and Differential Diagnosis of Alzheimers, Frontotemporal, and Lewy Body Dementias: A Systematic Review
Authors: De Keulenaer Stephanie , Van Mossevelde Sara , Van den Bossche Tobi , Crossiers David , Cras Patrick , Ellender Tommas , Bruffaerts Rose
Published: September 2024

Background An early and accurate diagnosis is crucial to provide optimal patient care in neurodegenerative diseases. Although an EEG shows advantages in availability and cost compared to the current diagnostic tools, it is not routinely used in clinical practice. Previous reviews have either focused on single disease populations and/or solely on resting state EEG. To evaluate the utility of EEG for early diagnosis and differential diagnosis, we conducted a systematic review across Alzheimers disease (AD), Frontotemporal Dementia (FTD) and Lewy Body Dementia (DLB). Methods We searched databases Pubmed, Cochrane, Web of Science, and Scopus for articles published from 2000 to 2023 investigating resting-state and task-based EEG-markers in biomarker-proven AD, FTD and DLB. Results Our search yielded a total of 12010 studies, of which 71 papers were eligible: 34 on AD, 18 on DLB and 9 on FTD. Slowing of the frequency spectrum was a common observation across diseases, achieving excellent sensitivity in AD and DLB. Research on FTD was limited and with varying results in the discrimination from healthy controls, although connectivity analysis and microstates are promising avenues. In differential diagnosis, both spectral and connectivity metrics show encouraging results. Task-based EEG emerges as a promising tool in early AD. Conclusion EEG shows promise as a cost-effective, non-invasive tool for early detection and differential diagnosis. Future research should aim to collect standardized data from multicentric cohorts, across multiple diseases and stages, and explore the neural underpinnings of these diseases, to improve interpretability of the findings.
Gaps and Opportunities for Data Systems and Economics to Support Priority Setting for Climate-Sensitive Infectious Diseases in Sub-Saharan Africa: A Rapid Scoping Review
Authors: Delight Ellie A. , Brunn Ariel A. , Ruiz Francis , Gerard Jessica , Falconer Jane , Liu Yang , Bah Bubacarr , Bett Bernard , Uzochukwu Benjamin , Oloko Oladeji K. , Njuguna Esther , Murray Kris A.
Published: September 2024

Climate change alters risks associated with climate-sensitive infectious diseases (CSIDs) with pandemic potential. This poses additional threats to already vulnerable populations, further amplified by intersecting social factors, such as gender and socioeconomic status. Currently, critical evidence gaps and inadequate institutional and governance mechanisms impact on the ability for African States to prevent, detect and respond to CSIDs. The aim of this study was to explore the role of data systems and economics to support priority setting for CSID preparedness in sub-Saharan Africa.

We conducted a rapid scoping review to identify existing knowledge and gaps relevant to economics and data systems. A literature search was performed across six bibliographic databases in November 2023. A list of 14 target pathogens, identified by the World Health Organization as Public Health Emergencies of International Concern or R&D Blueprint Pathogens, was adopted and compared to a database of CSIDs to determine relevant inclusion criteria. Extracted data were synthesised using bibliometric analysis, thematic topic categorisation, and narrative synthesis to identify research needs, evidence gaps, and opportunities for priority setting.

We identified 68 relevant studies. While African author involvement has been increasing since 2010, few studies were led by senior authors from African institutions. Data system studies (n = 50) showed broad coverage across CSIDs and the WHO AFRO region but also a high degree of heterogeneity, indicating a lack of clearly defined standards for data systems related to pandemic preparedness. Economic studies (n = 18) primarily focused on COVID-19 and Ebola and mostly originated from South Africa. Both data system and economic studies identified limited data sharing across sectors and showed a notable absence of gender sensitivity analyses. These significant gaps highlight important opportunities to support priority setting and decision-making for pandemic preparedness, ultimately leading to more equitable health outcomes.
Don’t Jump to Faulty Conclusions: Using the Synthetic Control Method to Evaluate the Effect of a Counterfactual Lockdown in Sweden
Authors: Herby Jonas
Published: September 2024

Several studies based on the Synthetic Control Method (SCM) link the many COVID-19 deaths in Sweden during the spring of 2020 to its decision not to lock down. These studies predominantly rely on a limited pre-intervention period and tend to focus on the very short run neglecting that Swedish health authorities emphasized that their public health strategy was designed for the long run. This paper handles these shortcomings expanding both the pre- and post-intervention period considerably using weekly mortality rates. I find no significant effect of the absence of lockdown on COVID-19 mortality neither in the short or long run. Using the timing of the winter holiday as a proxy for the extent/spread of COVID-19 in societies before lockdown – a variable which is unobservable due to limited testing – I suggest that the effect of lockdowns found in earlier studies using Sweden as a control are likely to be partially driven by unobserved variables rather than policies.
APOE4impact on soluble and insoluble tau pathology is mostly influenced by amyloid-beta
Authors: Cicognola Claudia , Salvadó Gemma , Smith Ruben , Palmqvist Sebastian , Stomrud Erik , Betthauser Tobey , Johnson Sterling , Janelidze Shorena , Mattsson-Carlgren Niklas , Hansson Oskar , Binette Alexa Pichet
Published: September 2024

TheAPOE4allele is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD). WhileAPOE4is strongly associated with amyloid-beta (Aβ) accumulation, its relationship with tau accumulation is less understood. Studies evaluating the role ofAPOE4on tau accumulation have shown conflicting results, particularly regarding the independence of these associations from Aβ load. To clarify the relations betweenAPOE4,Aβ and tau, we examined three independent longitudinal cohorts (the Swedish BioFINDER-1, BioFINDER-2 and WRAP cohorts) in which participants had cross-sectional and longitudinal measures of tau tangles (tau-PET; temporal meta-ROI and entorhinal) or soluble p-tau (p-tau217), Aβ-PET andAPOEgenotype. The study included a total of 1370 cognitively unimpaired (CU) and 449 mild cognitive impairment (MCI) subjects, followed longitudinally with tau-PET and p-tau217.APOE4carriers accounted for 40.2-50% of the cohorts. Different linear regressions (cross-sectional) and linear mixed-effect models (longitudinal) with tau measures as outcomes were fitted to test the effect ofAPOE4as independent predictor, as well as in combination with baseline Aβ load or the interaction term betweenAPOE4and Aβ load. All models included age, sex and cognitive status as covariates.

We found no independent effects of theAPOE4carriership on insoluble tau aggregates in either cohort (BioFINDER-2 or WRAP), both on cross-sectional and longitudinal tau-PET levels in the temporal meta-ROI, when Aβ was present in the model (p=0.531-0.949). Aβ alone was the best predictor of insoluble tau accumulation, and there was no interaction betweenAPOE4and Aβ on tau-PET. Similarly, no independent effects of theAPOE4carriership on baseline (p=0.683-0.708) and longitudinal (p=0.188-0.570) soluble p-tau217 were observed when Aβ was included in the model in BioFINDER-1 and WRAP. No interaction betweenAPOE4and Aβ on soluble p-tau217 was observed. Furthermore, mediation analysis revealed that Aβ load fully mediated most associations betweenAPOE4and tau (46-112%, either cross-sectional or longitudinal tau-PET or soluble p-tau217). In the largest cohort (BioFINDER-2), looking atAPOE4groups based on the number of ε4 alleles, we found an interaction between APOE4 homozygotes only and Aβ on tau-PET levels at baseline and over time.

In conclusion, althoughAPOE4is strongly associated with Aβ aggregation, it seems to be minimally associated with longitudinal changes in soluble or insoluble p-tau levels at a given level of Aβ pathology, confirming the primacy of Aβ in driving tau pathology.
Self-reported Health Literacy, Digital Literacy, and Barriers to accessing care at a Safety Net Breast Surgical Oncology Clinic
Authors: Burke Jamie , Higgins Madeline G , Vemuru Sudheer R , Adams Monica , Leonard Laura , Taft Nancy , Ahrendt Gretchen , Jaiswal Kshama , Rojas Kristin , Miles Randy , Tevis Sarah E.
Published: September 2024

Background

Sociodemographic factors, including language, education, race, and insurance status, significantly influence patient outcomes following breast surgery, especially in safety-net hospitals (SNHs) that serve vulnerable populations.

Objective

To assess the sociodemographic composition of a breast surgical oncology clinic at an urban SNH and evaluate how these factors impact digital literacy, health literacy, and access to care.

Methods

English and Spanish-speaking adult female patients at an urban SNH breast surgical oncology clinic between August and October 2022 completed a survey assessing digital and health literacy, barriers to care, and sociodemographic information. Descriptive statistics and comparative analyses were performed using Chi-squared and Fisher’s exact tests.

Results

Of 127 invited patients, 95 (75%) completed the survey. The median age was 50 years. Fifty-six percent identified as Hispanic, 43% preferred Spanish, and 40% had less than a high school education. Health literacy was lower among Spanish-speaking, older, and less-educated patients. Digital literacy was also lower among these groups, with notable disparities in access to computers, the internet, and smartphones.

Conclusion

Significant disparities in health and digital literacy exist among vulnerable breast cancer patients at SNHs, particularly among Spanish-speaking, older, and less-educated individuals. Targeted interventions to improve education, access to digital resources, and supportive services are essential to ensure equitable care and improve health outcomes for these populations.
CRISPR-Cas12a2-based rapid and sensitive detection system for target nucleic acid
Authors: Yu Helin , Feng Meng , Liu Chuncao , Wang Feifei , Sui Guodong , Jing Wenwen , Cheng Xunjia
Published: September 2024

Infectious diseases are extremely important public health issues, where the design of effective, rapid, and convenient detection platforms is critical. In this study, we used conventional PCR coupled with SuCas12a2, a novel Cas12 family RNA-targeting nuclease, to develop a detection approach. SuCas12a2 possesses collateral cleavage activity and cuts the additional single-stranded RNA (ssRNA) added to the reaction system once the ternary complex RNA-SuCas12a2-CRISPR RNA (crRNA) is formed. SuCas12a2 is specifically activated, where the cleaved fluorescent-labeled probes release fluorescent signals, with the strength of the fluorescent signal being proportional to the concentration of nucleic acids specifically bound to crRNA. Simultaneous transcription and SuCas12a2 detection can be performed in a single tube by introducing the T7 promoter sequence into the forward primer.Entamoeba histolyticawas used to evaluate the performance of the platform. PCR-SuCas12a2 has excellent capabilities, including high specificity with no cross-reactivity from other species and ultra-sensitivity that achieves a detection of one copy per reaction. There were five samples from amoebiasis patients confirmed by indirect immunofluorescence assay that were used as proof specimens, where the PCR-SuCas12a2 assay demonstrated 100% specificity. Furthermore, we replaced conventional PCR with recombinase polymerase amplification (RPA) to simplify the procedure for producing amplicons harboring the T7 promoter sequence. The sensitivity of the RPA-SuCas12a2 assay was 102copies per reaction, which was inferior to PCR-SuCas12a2, and demonstrated 100% specificity. The technique shows robust performance and suggests great potential for point-of-care testing of other pathogens to facilitate effective management and control of the spread of diseases.

Abstract Figure

Figure abstract
A novel method for characterizing cell-cell interactions at single-cell resolution reveals unique signatures in blood T cell-monocyte complexes during infection
Authors: Kang Ningxin , Chawla Ashu , Hillman Hannah , Tippalagama Rashmi , Kim Cheryl , Mikulski Zbigniew , Seumois Grégory , Vijayanand Pandurangan , Scriba Thomas J , De Silva Aruna D , Balmaseda Angel , Harris Eva , Weiskopf Daniela , Sette Alessandro , Arlehamn Cecilia Lindestam , Peters Bjoern , Burel Julie G
Published: September 2024

Communication between immune cells through direct contact is a critical feature of immune responses. Here, we developed a novel high-throughput method to study the transcriptome and adaptive immune receptor repertoire of single cells forming complexes without needing bioinformatic deconvolution. We found that T cells and monocytes forming complexes in blood during active tuberculosis (TB) and dengue hold unique transcriptomic signatures indicative of TCR/MCH-II immune synapses. Additionally, T cells in complexes showed enrichment for effector phenotypes, imaging and transcriptomic features of active TCR signaling, and increased immune activity at diagnosis compared to after anti-TB therapy. We also found evidence for bidirectional RNA exchange between T cells and monocytes, since complexes were markedly enriched for “dual-expressing” cells (i.e., co-expressing T cell and monocyte genes). Thus, studying immune cell complexes at a single-cell resolution offers novel perspectives on immune synaptic interactions occurring in blood during infection.

Graphical Abstract
Properties of DNA in concentrated aqueous solutions of LiCl suggest transition to C-DNA
Authors: Mazur Alexey K. , Maaloum Mounir , Gladyshev Eugene
Published: September 2024

C-DNA represents a canonical DNA form related to B-DNA. While C-DNA is known to exist in air-dried fibers, its occurrence in aqueous solutions remains subject to debate. In fibers, the transition from B- to C-DNA is promoted by reduced hydration in the presence of certain monovalent cations (most notably Li+), and this process is generally associated with an increase in the helical twist. To understand if the B-to-C transition can occur in liquid media in principle, we analyzed properties of several circular DNA substrates in aqueous solutions with varying concentrations of LiCl (0.1-8 M). To this end, we estimated changes in the helical twist directly from circular dichroism (CD) spectra of a large supercoiled plasmid and, in parallel, assayed conformational changes in DNA minicircles by atomic force microscopy (AFM). We found that the helical twist increased continuously over the entire range of tested LiCl concentrations, without being subject to saturation even at 8 M LiCl. The overall increase in the helical twist was compatible with the B-to-C transition occurring in solution at a concentration of LiCl of about 8 M, suggesting that C-DNA should be stable above this level.
Expanding Automated Multiconformer Ligand Modeling to Macrocycles and Fragments
Authors: Flowers Jessica , Echols Nathaniel , Correy Galen , Jaishankar Priya , Togo Takaya , Renslo Adam R. , van den Bedem Henry , Fraser James S. , Wankowicz Stephanie A.
Published: September 2024

Small molecule ligands exhibit a diverse range of conformations in solution. Upon binding to a target protein, this conformational diversity is generally reduced. However, ligands can retain some degree of conformational flexibility even when bound to a receptor. In the Protein Data Bank (PDB), a small number of ligands have been modeled with distinct alternative conformations that are supported by X-ray crystallography density maps. However, the vast majority of structural models are fit to a single ligand conformation, potentially ignoring the underlying conformational heterogeneity present in the sample. We previously developed qFit-ligand to sample diverse ligand conformations and to select a parsimonious ensemble consistent with the density. While this approach indicated that many ligands populate alternative conformations, limitations in our sampling procedures often resulted in non-physical conformations and could not model complex ligands like macrocycles. Here, we introduce several improvements to qFit-ligand, including the use of routines within RDKit for stochastic conformational sampling. This new sampling method greatly enriches low energy conformations of small molecules and macrocycles. We further extended qFit-ligand to identify alternative conformations in PanDDA-modified density maps from high throughput X-ray fragment screening experiments. The new version of qFit-ligand improves fit to electron density and reduces torsional strain relative to deposited single conformer models and our previous version of qFit-ligand. These advances enhance the analysis of residual conformational heterogeneity present in ligand-bound structures, which can provide important insights for the rational design of therapeutic agents.