bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute postoperative pain prevalence and intensity in the first 72 hour in Dessie Comprehensive Specialized Hospital, Ethiopia: a prospective single center observational study
Authors: Timerga Sara , Befkadu Aynalem , Seyoum Fetene
Published: January 2024

Background:

Postoperative pain is poorly studied in developing countries. Severe pain after surgery remains a major problem, occurring in 50–70% of the patients. Differences exist across countries. Despite numerous published studies, the degree of pain following many types of surgery in everyday clinical practice is unknown. To improve postoperative pain-treatment and develop procedure-specific, optimized pain-treatment protocols, the prevalence and severity of postoperative pain must first be identified.

Objective:

This study aimed to determine the prevalence and intensity of acute postoperative pain and the practice of postoperative pain management.

Methods:

A total of 180 patients were enrolled in the study, with 160 calculated using a single population proportion formula and a 10% attrition rate added, with proportionate stratification according to the size of each ward to obtain the number of participants from each specialty ward. A multistage sampling with stratified proportionate at the initial stages and a simple random sampling technique at the final stage was used. The patients completed a numerical pain rating scale for pain immediately after surgery for the first 72 h after surgery. The prevalence of mild, moderate, or severe pain was calculated. The evaluation was performed at eight time points including immediately after surgery: T2, T4, T8, T12, T24, T48, and T72.

Result:

The prevalence of severe pain in patients who underwent elective surgery in the study period measured by numeric rating scale was 21.6, 43.9, 45.6, 28.9, 39.4, 10.5, and 13.4% at 2nd, 4th, 8th, 12th, 24th, 48th and 72 h, respectively.

Conclusion:

The prevalence of moderate-to-severe pain within 72 h postoperatively was slightly lower than that other studies conducted in Ethiopia reported. This was still high, indicating better pain management in the postoperative period. Involvement of the anesthetist in pain management is crucial for better patient management.
A qualitative study of perfectionism among self-identified perfectionist women with nonmetastatic breast cancer
Authors: Banville Catherine , Massicotte Véronique , Caplette-Gingras Aude , Langlois Frédéric , Gouin Jean-Philippe , Flett Gordon , Molnar Danielle S. , Lemieux Julie , Savard Josée
Published: January 2024

Background:

Receiving a cancer diagnosis can lead to various psychosocial disturbances. Perfectionism is associated with several psychological problems in the general population, but its role in cancer remains to be assessed. This exploratory qualitative descriptive study aims to examine the role of perfectionism as a vulnerability factor underlying the psychosocial difficulties encountered by people with cancer.

Methods:

A total of 10 women with nonmetastatic breast cancer who self-identified as perfectionists were recruited at the end of their radiation therapy to take part in a focus group or an individual interview.

Results:

The hybrid inductive-deductive thematic analysis revealed the following themes: (1) various dimensions of perfectionism; (2) low self-compassion; (3) control seeking; (4) low self-disclosure; (5) low social support seeking; (6) various coping strategies; (7) relative stability of perfectionism after cancer; (8) need to be a perfect patient; (9) negative psychological impacts; and (10) low interest in an intervention targeting perfectionism.

Conclusions:

This exploratory study psychosocial difficulties that may be related to perfectionism in patients with breast cancer, from both a systemic and an individual perspective.
Circulating levels of advanced glycation end products in females with polycystic ovary syndrome: a meta-analysis
Authors: Bahreiny Seyed Sobhan , Ahangarpour Akram , Aghaei Mojtaba
Published: January 2024

Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by a hormonal imbalance that affects females of reproductive age. The association between advanced glycation end products (AGEs) and PCOS has attracted considerable attention in recent years, highlighting the potential of AGEs as biomarkers for this disorder. In the present systematic review and meta-analysis, we aimed to examine the association between AGEs and PCOS, evaluate their potential as biomarkers, and improve our understanding of the pathophysiology of PCOS and its associated metabolic complications. A literature search was performed using various databases from January 2000 to March 2023 to identify relevant studies investigating the association between AGEs and PCOS. Pooled effect estimates were calculated using standardized mean differences (SMD) with 95% confidence intervals (CIs). Sub-group and meta-regression analyses were performed to examine potential sources of heterogeneity. The meta-analysis included six studies with a total of 623 participants. Our results revealed a significant increase in circulating AGE levels in females with PCOS compared to healthy females (SMD = 2.35; 95% CI: 1.10–3.60; P <0.001). Significant heterogeneity was observed between the studies (I
2 = 96.37%; P <0.001), indicating the presence of several factors influencing the association. Sub-group analyses based on body mass index, age, and homeostatic model assessment for insulin resistance indicated differential effects of AGEs on specific sub-groups. This systematic review and meta-analysis support the association between elevated AGE levels and PCOS, thereby suggesting the potential role of AGEs as biomarkers in PCOS.
Craniofacial Injuries in Swimming and Water Sports: Implications for Prevention
Authors: Mangal Rohan , Desai Anshumi , Treger Dylan , Gompels Matthew , Thaller Seth
Published: January 2024

Introduction:

Water-related recreational activities, including swimming and diving, are widespread. However, they carry a significant risk of craniofacial injuries. Despite the popularity of these activities, comprehensive data on injuries beyond drowning remain scant. This study addresses this gap by providing valuable epidemiological insight into the nature, prevalence, and demographic patterns of craniofacial injuries related to water sports activities.

Methods:

The authors queried the NEISS database for craniofacial injuries related to swimming, diving, and water sports from 2013 to 2022. Data were analyzed for demographics, anatomic locations of injuries, and the activities leading to these injuries.

Results:

Between 2013 and 2022, a total of 952,111 craniofacial injuries were associated with swimming and water sports. Of these, 510,706 (53.6%) were male patients, and 441,405 (46.4%) were female. This indicates that males were 1.16 times more likely to sustain such injuries. The age groups most affected were 0 to 9 and 10 to 19 years. Anatomic locations impacted were as follows: ears (58.1%), head (16.8%), face (13.9%), neck (4.8%), eyeballs (4.4%), and mouth (2%). Leading causes were identified as swimming and water sports activities (66.5%), swimming pools and equipment (28.2%), diving or diving boards (4.7%), and scuba diving (0.5%). Notably, 89.2% of patients with diving-related injuries and 99.1% with swimming-related injuries were not admitted to the hospital.

Conclusions:

This study offers critical epidemiological data to supplement targeted prevention strategies and resource allocation in managing craniofacial injuries associated with water activities. The findings highlight the urgent need for specialized care and serve as a foundation for future preventive initiatives.
Exercise alters molecular rhythms in the central nervous system that negatively correlate with depression-like behavior
Authors: Yu Lei , Xue Haonan , Li Zhongtang
Published: January 2024

Major depressive disorder (MDD) ranks among the top 10 leading causes of death. However, exercise is known to improve depressive symptoms but the mechanism responsible is still unknown. To date, numerous studies have shown that molecular rhythms and exercise are associated with MDD. Thus, we hypothesized that exercise could affect the expression of central nervous system clock genes to improve depressive symptoms. Ninety adult male Sprague–Dawley rats (250 g) were divided into a control Normal Group, an unpredictable chronic mild stress (CMS) treated CMS Group and an Exercise Group, which was intervened by a moderate-intensity exercise training on a treadmill at 2 p.m. every day for 4 weeks after CMS treatment. The open field test, elevated plus maze and forced swim test were employed to test mood-related behaviors. The telemetry recording method recorded voluntary locomotor activity and core body temperature. Expression of core clock genes in the suprachiasmatic nucleus (SCN) was tested by qRT-PCR. Compared with the CMS Group, depressive symptoms were improved in the Exercise Group (P < 0.05). Moreover, the periodic changes of molecular rhythms in the Exercise Group were close to those of rats in Normal Group. Next, exercise increased oscillations of expression of core clock genes in SCN after CMS treatment, and the amplitudes of core clock gene expression oscillations were negatively correlated with depressive-like behavior. Our findings suggested that exercise could change the expressions of central clock genes in MDD animals, and this effect was positively correlated with the improvement of depressive symptoms by exercise.
Investigating How East Asian Medical and Biomedical Systems Can Communicate: A Qualitative Exploration of How East Asian Medicine Concepts Can be Used in Modern Health Research
Authors: Macbeth JoHannah , Conboy Lisa , Engels Maria , Burack Rachel
Published: January 2024

Purpose

There is much published science supporting East Asian Medicine (EAM) as a treatment for many health issues. Public Health has made great advancement in understanding the effects of health disparities globally. East Asian Medical Models offer additional ways to think about health disparities.

Methods

Twelve participants who are Biomedicine and/or Eastern Medicine experts or social scientists were identified from the research team’s network. Our goal in this purposive sample was to represent diverse backgrounds, educational and professional experience, expertise, age, gender, and geographic location. Following IRB approval, all potential subjects identified for recruitment agreed to participate and were consented. Semi-structured interviews were conducted with each subject on the Zoom © platform, and ranged between 60 and 90 minutes. Recordings were transcribed and checked for accuracy, and double coded for themes. Any disagreement in coding was addressed in discussion between the coders. We assessed the data for saturation on key content areas, and when finding repetition of themes, chose to complete the stage of data analysis. Next, we employed a thematic analysis to better understand the key concepts.

Results

Seven main themes emerged from the interviews. These are necessary areas to consider when considering health disparities: THREE TREASURES, PATIENT PROVIDER RELATIONSHIP, ASSESSMENT OF HEALTH STATUS in EAM, PRENATAL ESSENCE, POSTNATAL ESSENCE, DETERMINANTS OF HEALTH, BELONGING.

Conclusions

Scientific discovery and health care will improve with improvement in communication between medical practitioners and scientists from EAM and Biomedicine (BM). We use our data to consider ways that the EAM model of health can add to our understanding of the effects social disparities on health.
Beyond a Unitary Construct: Dissecting Stopping Behaviour in Two Bird Species
Authors: Troisi CA , Vernouillet A , Allaert R , Knoch S , Martel A , Lens L , Verbruggen F
Published: January 2024

The ability to stop behaviour is essential for adapting to changes in the environment, a principle that holds true across various species. While traditionally considered a unitary psychological construct, recent studies indicate that this ability is multifaceted. Our research evaluates this multifaceted nature using three tasks that measure stopping in different contexts in two related gull species: herring gulls (Larus argentatus) and lesser black-backed gulls (L. fuscus). These species were selected for their distinct migration and foraging strategies, offering a unique lens through which to examine behavioural adaptations. Across tasks and species, we conceptualised stopping as a race between a go and a stop runner, and predicted correlations based on the type of stop stimulus, the relative timing of the go and the stop stimuli, and the type of action that needed to be stopped. We found correlations between measures of ‘going’ across tasks, but there was less consistency in measures of ‘stopping’. Furthermore, we observed significant differences in ‘going’ and ‘stopping’ behaviours that were specific to each species, which may be linked to their migration and foraging strategies. These findings highlight the importance of considering the multifaceted nature of stopping in evolutionary and behavioural studies.
Surface Patterned Omniphobic Tiles (SPOTs): a versatile platform for scalable liquid handling
Authors: Shiri Samira , Qazi Mohsin J , Tan Shenghao , Albo Jon , Chen Arnold , Fukuda Rena , Jain Mika S , Nchinda Nkazi , Menesses Mark , Ahmed Ghada , Gallegos Arynn O , Gangishetty Mahesh K , Congreve Daniel N , Cira Nate J
Published: January 2024

Manipulating liquids is a ubiquitous need for experiments across numerous scientific disciplines. To overcome limitations of current methods, we introduce Surface Patterned Omniphobic Tiles (SPOTs). This platform combines geometry and surface engineering, building on discontinuous wetting approaches to leverage capillarity for metering liquids. The SPOTs platform allows manipulation of hundreds to thousands of independent experiments without expensive equipment or large consumable costs. These devices can handle a wide range of liquid types and volumes (<10 nanoliters to >10 microliters) with better precision than pipetting. The platform is inexpensive and easy to fabricate, fast and intuitive to use, and cross-compatible with existing microwell plate layouts. We demonstrate how these capabilities facilitate diverse experiments including testing antibiotic combinations for synergy and antagonism, material screening of perovskites, and genotyping microbial isolates. We anticipate SPOTs will enable users from disparate domains to quickly and easily run a wide range of high-throughput experiments.
Transgenic αβ TCR tonic signaling is leukemogenic while strong stimulation is leukemia-suppressive
Authors: Catarino Telmo A. , Pacheco-Leyva Ivette , Pereira João L. , Baessa Marina , dos Santos Nuno R.
Published: January 2024

The pre-T cell receptor (TCR) and TCR complexes are frequently expressed in T-cell acute lymphoblastic leukemia (T-ALL), an aggressive T cell precursor malignancy. Although mutations in TCR components are infrequent in T-ALL, earlier research indicated that transgenic αβ TCR expression in mouse T cell precursors promoted T-ALL development. However, we recently found that stimulation of TCR signaling in T-ALL induced leukemic cell apoptosis and suppressed leukemia. Our aim was to elucidate if a given αβ TCR complex has a dual role in leukemogenesis depending on the nature of the stimulus. We demonstrate that transgenic expression of the Marilyn αβ TCR, specific for the H-Y male antigen presented by major histocompatibility complex class II, triggers T-ALL development exclusively in female mice. This T-ALL exhibitedNotch1mutations,Cdkn2acopy number loss, immature immunophenotype and infiltrated both lymphoid and non-lymphoid organs. Furthermore, leukemic cells expressed surface CD5, a marker of tonic TCR signaling. T-ALL efficiently developed inRag2-deficient Marilyn transgenic females, indicating that Rag2-mediated recombination is not implicated in this T-ALL model. Remarkably, exposure of Marilyn female T-ALL to male antigen in recipient mice resulted in T-ALL apoptosis and prolonged mouse survival. These findings underscore that the same αβ TCR complex has a dual role in T-ALL in that its tonic stimulation is leukemogenic, while strong stimulation is leukemia-suppressive.
A low-cost protocol for reconditioning of deep-brain neural microelectrodes with material failure for electrophysiology recording
Authors: Rezayat Leila , Ghajar Mohammad Hossein , Naji Alireza , Nourozi Jalaledin , Dehaqani MohammadReza Abolghasemi , Rezayat Ehsan
Published: January 2024

Up to now, a large variety of neural microelectrodes are developed. Although there are a lot of published works in this area, the majority of them are about the fabrication methods and rarely discuss the reconditioning procedure or how to re-use the electrodes that their performance is decreased because of material failure. In this paper, firstly, it is answered that why the performance of neural microelectrodes decreases. Secondly, a general low-cost protocol for reconditioning and re-using electrodes are proposed that can be utilized for the most types of electrodes with material failure. Lastly, the proposed reconditioning protocol is applied experimentally to single-site tungsten microelectrodes to demonstrate the effectiveness of the protocol. Neural signal recording Results clearly indicate that a large number of electrodes can be reconditioned well.
Vertically inherited microbiota and environment modifying behaviors conceal genetic variation in dung beetle life history
Authors: Rohner Patrick T. , Moczek Armin P.
Published: January 2024

Diverse organisms actively manipulate their (sym)biotic and physical environment in ways that feedback on their own development. However, the degree to which these processes affect microevolution remains poorly understood. The gazelle dung beetle both physically modifies its ontogenetic environment and structures its biotic interactions through vertical symbiont transmission. By experimentally eliminating i) physical environmental modifications, and ii) the vertical inheritance of microbes, we assess how environment modifying behavior and microbiome transmission shape heritable variation and evolutionary potential. We found that depriving larvae from symbionts and environment modifying behaviors increased additive genetic variance and heritability for development time but not body size. This suggests that larvae’s ability to manipulate their environment has the potential to modify heritable variation and to facilitate the accumulation of cryptic genetic variation. This cryptic variation may become released and selectable when organisms encounter environments that alter the degree to which they can be manipulated. Our findings also suggest that intact microbiomes, which are commonly thought to increase genetic variation of their hosts, may instead reduce and conceal heritable variation. More broadly, our findings highlight that the ability of organisms to actively manipulate their environment may affect the potential of populations to evolve when encountering novel, stressful conditions.
Dynamics, Electrostatics, and Thermodynamics of Base Pairing at theLTR-IIIQuadruplex:Duplex Junction
Authors: Michel Haley M. , Lemkul Justin A.
Published: January 2024

G-quadruplexes (GQs) play key regulatory roles within the human genome and have also been identified to play similar roles in other eukaryotes, bacteria, archaea, and viruses. Human immunodeficiency virus 1 (HIV-1), the etiological agent of acquired immunodeficiency syndrome (AIDS), can form two GQs in its long terminal repeat (LTR) promoter region, each of which act to regulate viral gene expression in opposing manners. The major LTR GQ, calledLTR-III, is a distinct hybrid GQ containing a 12-nucleotide duplex loop attached to the quadruplex motif. The resulting quadruplex:duplex junction (QDJ) has been hypothesized to serve as a selective drug targeting site. To better understand the dynamics of this QDJ, we performed conventional and enhanced-sampling molecular dynamics simulations using the Drude-2017 force field. We observed unbiased and reversible formation of additional base pairs in the QDJ, between Ade4:Thy14 and Gua3:Thy14. Both base pairs were electrostatically favored but geometric constraints within the junction may drive the formation of, and preference for, the Ade4:Thy14 base pair. Finally, we demonstrated that the base pairs are separated only by small energy barriers that may enable transitions between both base-paired states. Together, these simulations provide new insights into the dynamics, electrostatics, and thermodynamics of theLTR-IIIQDJ.

SIGNIFICANCE

Here, we characterize the quadruplex:duplex junction of the HIV-1LTR-IIIG-quadruplex. We find that two additional base pairs can form in the junction and are driven by electrostatic, thermodynamic, and geometric factors. G-quadruplexes containing such junctions are rather recent discoveries, and it has been proposed that these junctions can act as selective targets for drugs. These results further identify distinct chemical and electrostatic characteristics that can be used to guide drug design studies.
Cross-institutional HER2 assessment via a computer-aided system using federated learning and stain composition augmentation
Authors: Yang Chia-Hung , Chen Yung-An , Chang Shao-Yu , Hsieh Yu-Han , Hung Yu-Ling , Lin Yi-Wen , Lee Yi-Hsuan , Lin Ching-Hung , Lin Yu-Chieh , Lu Yen-Shen , Lin Yen-Yin
Published: January 2024

The rapid advancement of precision medicine and personalized healthcare has heightened the demand for accurate diagnostic tests. These tests are crucial for administering novel treatments like targeted therapy. To ensure the widespread availability of accurate diagnostics with consistent standards, the integration of computer-aided systems has become essential. Specifically, computer-aided systems that assess biomarker expression have thrusted through the widespread application of deep learning for medical imaging. However, the generalizability of deep learning models has usually diminished significantly when being confronted with data collected from different sources, especially for histological imaging in digital pathology. It has therefore been challenging to effectively develop and employ a computer-aided system across multiple medical institutions. In this study, a biomarker computer-aided framework was proposed to overcome such challenges. This framework incorporated a new approach to augment the composition of histological staining, which enhanced the performance of federated learning models. A HER2 assessment system was developed following the proposed framework, and it was evaluated on a clinical dataset from National Taiwan University Hospital and a public dataset coordinated by the University of Warwick. This assessment system showed an accuracy exceeding 90% for both institutions, whose generalizability outperformed a baseline system developed solely through the clinical dataset by 30%. Compared to previous works where data across different institutions were mixed during model training, the HER2 assessment system achieved a similar performance while it was developed with guaranteed patient privacy via federated learning.
Exploring Mechanisms of Lipid Nanoparticle-Mucus Interactions in Healthy and Cystic Fibrosis Conditions
Authors: Tafech Belal , Rokhforouz Mohammad-Reza , Leung Jerry , Sung Molly MH , Lin Paulo JC , Sin Don D , Lauster Daniel , Block Stephan , Quon Bradley S. , Tam Ying , Cullis Pieter , Feng James J , Hedtrich Sarah
Published: January 2024

Mucus forms the first defense line of human lungs, and as such hampers the efficient delivery of therapeutics to the underlying epithelium. This holds particularly true for genetic cargo such as CRISPR-based gene editing tools which cannot readily surmount the mucosal barrier. While lipid nanoparticles (LNPs) emerged as versatile non-viral gene delivery systems that could help overcome the delivery challenge, many knowledge gaps remain, especially for diseased states such as cystic fibrosis (CF).

This study provides fundamental insights into Cas9 mRNA or ribonucleoprotein-loaded LNP-mucus interactions in healthy and diseased states by assessing the impact of the genetic cargo, mucin sialylation, mucin concentration, ionic strength, pH, and polyethylene glycol (PEG) concentration and nature on LNP diffusivity leveraging experimental approaches and Brownian dynamics simulations.

Taken together, this study identifies key mucus and LNP characteristics that are critical to enabling a rational LNP design for transmucosal delivery.

Graphical Abstract
Evaluation of Deep Learning for predicting rice traits using structural and single-nucleotide genomic variants
Authors: Vourlaki Ioanna-Theoni , Ramos-Onsins Sebastián E. , Pérez-Enciso Miguel , Castanera Raúl
Published: January 2024

Structural variants (SVs) such as deletions, inversions, duplications, and Transposable Element (TE) Insertion Polymorphisms (TIPs) are prevalent in plant genomes and have played an important role in evolution and domestication, as they constitute a significant source of genomic and phenotypic variability. Nevertheless, most methods in quantitative genetics focusing on crop improvement, such as genomic prediction, consider Single Nucleotide Polymorphisms (SNPs) as the only type of genetic marker. Here, we used rice to investigate whether combining the structural and nucleotide genome-wide variation can improve prediction ability of traits when compared to using only SNPs. Moreover, we also examine the potential advantage of Deep Learning (DL) networks over Bayesian Linear models, which have been widely applied in genomic prediction. Specifically, the performance of BayesC and a Bayesian Reproducible Kernel Hilbert space regressions were compared to two different DL architectures, the Multilayer Perceptron, and the Convolution Neural Network. We further explore their prediction ability by using various marker input strategies and found that exploiting structural and nucleotide variation improves prediction ability on complex traits in rice. Also, DL models outperformed Bayesian models in 75% of the studied cases. Finally, DL systematically improved prediction ability of binary traits against the Bayesian models.
Magnetic Microtweezers for High-Throughput Bioseparation in Sub-Nanoliter Droplets
Authors: Dumas Simon , Alexandre Lucile , Richerd Mathilde , Serra Marco , Descroix Stéphanie
Published: January 2024

Multiomics studies at single-cell level require small volume manipulation, high throughput analysis and multiplexed detection, characteristics that droplet microfluidics can tackle. However, the initial step of molecules bioseparation remains challenging. Here, we describe a unique magnetic device to trap and extract magnetic particles in sub-nanoliter droplets, for compartmentalisation of detection steps. Relying on electrodeposition of NiFe structures and microfluidic manipulation, this technology has allowed the purification of genetic material at single-cell scale and was able to reach an extraction rate of 72% for a sample of purified oligonucleotides.
ProtHyena: A fast and efficient foundation protein language model at single amino acid Resolution
Authors: Zhang Yiming , Okumura Manabu
Published: January 2024

The emergence of self-supervised deep language models has revolutionized natural language processing tasks and has recently extended its applications to biological sequence analysis. Traditional models, primarily based on the Transformer and BERT architectures, demonstrate substantial effectiveness in various applications. However, these models are inherently constrained by the attention mechanism’s quadratic computational complexityO(L2), limiting their efficiency and the length of context they can process. Addressing these limitations, we introduceProtHyena, a novel approach that leverages the Hyena operator. This innovative methodology circumvents the constraints imposed by attention mechanisms, thereby reducing the time complexity to a subquadratic, enabling the modeling of extra-long protein sequences at the single amino acid level without the need to compress data. ProtHyena is able to achieve, and in many cases exceed, state-of-the-art results in various downstream tasks with only 10% of the parameters typically required by attention-based models. The architecture of ProtHyena presents a highly efficient solution for training protein predictors, offering a promising avenue for fast and efficient analysis of biological sequences.
Cell Type-Agnostic Optical Perturbation Screening Using Nuclear In-Situ Sequencing (NIS-Seq)
Authors: Fandrey Caroline I. , Konopka Peter , Jentzsch Marius , Zackria Afraa , Maasewerd Salie , Latz Eicke , Schmid-Burgk Jonathan L.
Published: January 2024

Genome-scale perturbation screening is widely used to identify disease-relevant cellular proteins serving as potential drug targets. However, most biological processes are not compatible with commonly employed perturbation screening methods, which rely on FACS- or growth-based enrichment of cells. Optical pooled screening instead uses fluorescence microscopy to determine the phenotype in single cells, and subsequently to identify individual perturbagens in the same cells. Published methods rely on cytosolic detection of endogenously expressed barcoded transcripts, which limits application to large, transcriptionally active cell types, and often relies on local clusters of clonal cells for unequivocal barcode assignment, thus precluding genome-scale screening for many biological processes. Nuclear In-Situ Sequencing (NIS-Seq) solves these shortcomings by creating bright sequencing signals directly from nuclear genomic DNA, enabling screening any nucleus-containing cell type at high density and high library complexity. We benchmark NIS-Seq by performing three genome-scale optical screens in live cells, identifying key players of inflammation-related cellular pathways.
Orthogonalized human protease control of secreted signals
Authors: Aldrete Carlos A. , Call Connor C. , Sant’Anna Lucas E. , Vlahos Alexander E. , Pei Jimin , Cong Qian , Gao Xiaojing J.
Published: January 2024

Synthetic circuits that regulate protein secretion in human cells could support cell-based therapies by enabling control over local environments. While protein-level circuits enable such potential clinical applications, featuring orthogonality and compactness, their non-human origin poses a potential immunogenic risk. Here, we developed Humanized Drug Induced Regulation of Engineered CyTokines (hDIRECT) as a platform to control cytokine activity exclusively using human-derived proteins. We sourced a specific human protease and its FDA-approved inhibitor. We engineered cytokines (IL-2, IL-6, and IL-10) whose activities can be activated and abrogated by proteolytic cleavage. We utilized species specificity and re-localization strategies to orthogonalize the cytokines and protease from the human context that they would be deployed in. hDIRECT should enable local cytokine activation to support a variety of cell-based therapies such as muscle regeneration and cancer immunotherapy. Our work offers a proof of concept for the emerging appreciation of humanization in synthetic biology for human health.
Penalized Semiparametric Estimation for Causal Inference with Possibly Invalid Instruments
Authors: Cao Yunlong , Wang Yuquan , Shi Dapeng , Chen Dong , Hu Yue-Qing
Published: January 2024

Summary

Inferring causal effects with unmeasured confounder is a main challenge in causal inference. Many researchers impose parametric assumptions on the distribution of unmeasured confounder. However, due to the unobservable nature of the unmeasured confounder, it is more reasonable to leave its distribution unrestricted. Another key challenge in causal inference is the involvement of invalid instrumental variables, which may lead to biased inference and possibly misleading scientific conclusions. To this end, we employ a flexible semiparametric model that allows for possibly invalid instruments without specifying the distribution of unmeasured confounder in this work. A penalized semiparametric estimator for causal effects is constructed and its oracle and asymptotic properties are well established for statistical inference. We evaluate the performance of the estimator through simulation studies, revealing that our proposed estimator exhibits asymptotic unbiasedness and robustness in estimating causal effects, along with consistent selection of invalid instruments. We also demonstrate its application using Atherosclerosis Risk in Communities Study data set, which further validates its robustness in the presence of invalid instruments. Additionally, we have implemented the proposed method in R, and the corresponding R code is available for free download.
Development of a Seizure Matching System for Clinical Decision Making in Epilepsy Surgery
Authors: Thomas John , Abdallah Chifaou , Jaber Kassem , Aron Olivier , Doležalová Irena , Gnatkovsky Vadym , Mansilla Daniel , Nevalainen Päivi , Pana Raluca , Schuele Stephan , Singh Jaysingh , Suller-Marti Ana , Urban Alexandra , Hall Jeffery , Dubeau François , Gotman Jean , Frauscher Birgit
Published: January 2024

Background and Objectives

The proportion of patients becoming seizure-free after epilepsy surgery has stagnated. Large multi-center stereo-electroencephalography datasets can potentially allow comparing a new patient to past similar cases and make clinical decisions with the knowledge of how similar cases were treated in the past. However, the complexity of these evaluations makes the manual search for similar patients in a large database impractical. We aim to develop an automated system that electrographically and anatomically matches seizures from a patient to those in a database. In addition, since we do not know what features define seizure similarity, particularly considering the various stereo-electroencephalography implantation schemes, we evaluate the agreement and features among experts in classifying seizure similarity.

Methods

We utilized SEEG seizures from consecutive patients who underwent stereo-electroencephalography for epilepsy surgery. Eight international experts evaluated seizure-pair similarity using a four-level similarity score through a graphical user interface. As our primary outcome, we developed and validated an automated seizure matching system by employing a leave-one-expert-out approach. Secondary outcomes included the inter-rater agreement and features for classifying seizure similarity.

Results

320 SEEG seizures from 95 patients were utilized. The seizure matching system achieved an area-under-the-curve of 0.82 (95% CI, 0.819-0.822), indicating its feasibility. Six distinct seizure similarity features were identified and proved effective: onset region, onset pattern, propagation region, duration, extent of spread, and propagation speed. Among these features, the onset region showed the strongest correlation with expert scores (Spearman’s rho=0.75,p<0.001). Additionally, the moderate inter-rater agreement confirmed the practicality of our approach: for the four-level classification, median agreement was 73.9% (interquartile range, 7%), and beyond-chance Gwet’s kappa was 0.45 (0.16); for the binary classification of similar vs. not related, agreement stood at 71.9% (4.7%) with a kappa of 0.46 (0.13).

Discussion

We demonstrate the feasibility and validity of a stereo-electroencephalography seizure matching system across patients, effectively mirroring the expertise of epileptologists. This novel system can identify patients with seizures similar to that of a patient being evaluated, thus optimizing the treatment plan by considering the treatment and the results of treating similar patients in the past, potentially resulting in an improved surgery outcome.
Metagenomic Analysis and Taxonomy of Bacteria Identified in Primary Endodontic Infections
Authors: Konjhodzic Alma , Brankovic Lajla Hasic , Tahmiscija Irmina , Korac Samra , Dzankovic Aida
Published: January 2024

The study explores the polymicrobial nature of primary endodontic infections using Illumina Next Generation Sequencing. Samples involved in research have been collected from root canals of the patients suffering from pulp and periapical inflammations with no history of endodontic interventions on affected teeth. The study revealed prevalence of different bacterial phyla, classes, orders, and species. Further work will show potential correlations between individual microbiotas and clinical diagnosis.
A nutritional immunity blockade controls extracellular bacterial replication inLegionella pneumophilainfections
Authors: Torres-Escobar Ascención , Wilkins Ashley , Juárez-Rodríguez María D , Circu Magdalena , Latimer Brian , Dragoi Ana-Maria , Ivanov Stanimir S.
Published: January 2024

The accidental human pathogenLegionella pneumophila(Lp) is the etiological agent for a severe atypical pneumonia known as Legionnaires’ disease. In human infections and animal models of disease alveolar macrophages are the primary cellular niche that supports bacterial replication within a unique intracellular membrane-bound organelle. The Dot/Icm apparatus – a type IV secretion system that translocates ∼300 bacterial proteins within the cytosol of the infected cell – is a central virulence factor required for intracellular growth. Mutant strains lacking functional Dot/Icm apparatus are transported to and degraded within the lysosomes of infected macrophages. The early foundational work from Dr. Horwitz’s group unequivocally established thatLegionelladoes not replicate extracellularly during infection – a phenomenon well supported by experimental evidence for four decades. Our data challenges the dogma in the field by demonstrating that macrophages and monocytes provide the necessary nutrients and support robustLegionellaextracellular replication. We show that the previously reported lack of Lp extracellular replication is not a bacteria intrinsic feature but rather a result of robust restriction by serum-derived nutritional immunity factors. Specifically, the host iron-sequestering protein Transferrin was identified as a critical suppressor of Lp extracellular replication in an iron-dependent manner. In iron-overload conditions or in the absence of Transferrin, Lp bypasses growth restriction by IFNψ-primed macrophages though extracellular replication. It is well established that certain risk factors associated with development of Legionnaires’ disease, such as smoking, produce a chronic pulmonary environment of iron-overload. Our work indicates that iron-overload could be an important determinant of severe infection by allowing Lp to overcome nutritional immunity and replicate extracellularly, which in turn would circumvent intracellular cell intrinsic host defenses. Thus, we provide evidence for nutritional immunity as a key underappreciated host defense mechanism inLegionellapathogenesis.
Stability and Volatility of Human Rest-Activity Rhythms: Insights from Very Long Actograms (VLAs)
Authors: Adhyapak Nandani , Abboud Mark A. , Rao Pallavi S.K. , Kar Ananya , Mignot Emmanuel , Delucca Gianluigi , Smagula Stephen F. , Krishnan Vaishnav
Published: January 2024

Importance

Wrist-worn activity monitors provide biomarkers of health by non-obtrusively measuring the timing and amount of rest and physical activity (rest-activity rhythms, RARs). The morphology and robustness of RARs vary by age, gender, and sociodemographic factors, and are perturbed in various chronic illnesses. However, these are cross-sectionally derived associations from recordings lasting 4-10 days, providing little insights into how RARs vary with time.

Objective

To describe how RAR parameters can vary or evolve with time (∼months).

Design, Setting and Participants

48 very long actograms (“VLAs”, ≥90 days in duration) were identified from subjects enrolled in the STAGES (Stanford Technology, Analytics and Genomics in Sleep) study, a prospective cross-sectional, multisite assessment of individuals > 13 years of age that required diagnostic polysomnography to address a sleep complaint. A single 3-year long VLA (author GD) is also described.

Exposures/Intervention

None planned.

Main Outcomes and Measures

For each VLA, we assessed the following parameters in 14-day windows: circadian/ultradian spectrum, pseudo-F statistic (“F”), cosinor amplitude, intradaily variability, interdaily stability, acrophase and estimates of “sleep” and non-wearing.

Results

Included STAGES subjects (n = 48, 30 female) had a median age of 51, BMI of 29.4kg/m2, Epworth Sleepiness Scale score (ESS) of 10/24 and a median recording duration of 120 days. We observed marked within-subject undulations in all six RAR parameters, with many subjects displaying ultradian rhythms of activity that waxed and waned in intensity. When appraised at the group level (nomothetic), averaged RAR parameters remained remarkably stable over a ∼4 month recording period. Cohort-level deficits in average RAR robustness associated with unemployment or high BMI (>29.4) also remained stable over time.

Conclusions and Relevance

Through an exemplary set of months-long wrist actigraphy recordings, this study quantitatively depicts the longitudinal stability and dynamic range of human rest-activity rhythms. We propose that continuous and long-term actigraphy may have broad potential as a holistic, transdiagnostic and ecologically valid monitoring biomarker of changes in chronobiological health. Prospective recordings from willing subjects will be necessary to precisely define contexts of use.
Asymptotic Freedom at the Berezinskii-Kosterlitz-Thouless Transition without Fine-Tuning Using a Qubit Regularization
Authors: Maiti Sandip , Banerjee Debasish , Chandrasekharan Shailesh , Marinkovic Marina K.
Published: January 2024

We propose a two-dimensional hard-core loop-gas model as a way to regularize the asymptotically free massive continuum quantum field theory that emerges at the Berezinskii-Kosterlitz-Thouless transition. Without fine-tuning, our model can reproduce the universal step-scaling function of the classical lattice XY model in the massive phase as we approach the phase transition. This is achieved by lowering the fugacity of Fock-vacuum sites in the loop-gas configuration space to zero in the thermodynamic limit. Some of the universal quantities at the Berezinskii-Kosterlitz-Thouless transition show smaller finite size effects in our model as compared to the traditional XY model. Our model is a prime example of qubit regularization of an asymptotically free massive quantum field theory in Euclidean space-time and helps understand how asymptotic freedom can arise as a relevant perturbation at a decoupled fixed point without fine-tuning.

Published by the American Physical Society
2024
Spectroscopic Evidence of Kondo-Induced Quasiquartet in
CeRh2As2
Authors: Christovam Denise S. , Ferreira-Carvalho Miguel , Marino Andrea , Sundermann Martin , Takegami Daisuke , Melendez-Sans Anna , Tsuei Ku Ding , Hu Zhiwei , Rößler Sahana , Valvidares Manuel , Haverkort Maurits W. , Liu Yu , Bauer Eric D. , Tjeng Liu Hao , Zwicknagl Gertrud , Severing Andrea
Published: January 2024

CeRh2As2 is a new multiphase superconductor with strong suggestions for an additional itinerant multipolar ordered phase. The modeling of the low-temperature properties of this heavy-fermion compound requires a quartet Ce3+ crystal-field ground state. Here, we provide the evidence for the formation of such a quartet state using x-ray spectroscopy. Core-level photoelectron and x-ray absorption spectroscopy confirm the presence of Kondo hybridization in CeRh2As2. The temperature dependence of the linear dichroism unambiguously reveals the impact of Kondo physics for coupling the Kramer’s doublets into an effective quasiquartet. Nonresonant inelastic x-ray scattering data find that the |Γ7−⟩ state with its lobes along the 110 direction of the tetragonal structure (xy orientation) contributes most to the multiorbital ground state of CeRh2As2.

Published by the American Physical Society
2024
Exploring new dimensions in OTT consumption: an empirical study on perceived risks, descriptive norms and goal-directed behaviour
Authors: Sahu Garima , Singh Gurinder , Singh Gurmeet , Gaur Loveleen
Published: January 2024

Purpose

With over-the-top (OTT) streaming services rapidly transforming the media industry and saturating the market, the authors' study seeks to enrich the goal-directed behaviour model by exploring how perceived risks and descriptive norms influence OTT consumption.

Design/methodology/approach

Survey data from OTT subscribers were collected online to assess their risk behaviours. The 353 responses obtained were analysed with SmartPLS, validating the structural equation modelling (SEM) through structural and measurement model verification.

Findings

The authors' findings illustrate that descriptive norm, perceived behavioural control, as well as positive and negative anticipated emotion (NEM) and attitude, contribute positively to the desire to engage with OTT streaming services. Interestingly, the authors' study contradicts common assumptions, revealing that subjective norms do not significantly impact the propensity to utilise OTT services. This counterintuitive finding necessitates a reconsideration of prevalent theories and contributes to a nuanced understanding of OTT adoption determinants.

Research limitations/implications

The data gathering for this study were conducted from the perspective of a single nation. Therefore, caution must be exercised when generalising this study's results.

Practical implications

The practical ramifications of this research are vast, providing OTT service providers and marketers with actionable insights to maximise user engagement and navigate perceived risks related to OTT service adoption and consumption.

Originality/value

This study's exploration of perceived risks and descriptive norms enhances the goal-directed behaviour model's breadth, facilitating a holistic comprehension of the constructs shaping OTT consumption behaviours. It would be the first attempt to combine perceptual, affective and behavioural factors and perceived risks to understand the user's predisposition to engage in OTT streaming services.
ESG investing versus the market: returns and risk analysis and portfolio diversification in Latin-America
Authors: Alvarez-Perez Hugo , Diaz-Crespo Regina , Gutierrez-Fernandez Luis
Published: January 2024

Purpose

This study aims to examine the performance of environmental, social and governance (ESG) equity indices in Latin America (LA), evaluating their risk-return characteristics in comparison to conventional benchmark indices.

Design/methodology/approach

Using a quantitative empirical approach, the authors analyze ESG equity indices from Brazil, Mexico, Chile, Peru and Colombia, employing metrics such as Sharpe, Sortino and Omega ratios to measure risk-adjusted returns. Regression analysis is employed to assess the replicability of ESG indices by benchmark indices. Monte Carlo simulations are conducted to explore the potential increase in risk-adjusted returns when ESG equity indices are incorporated into portfolios.

Findings

The study addresses critical questions for investors: Can ESG indices outperform their benchmarks? Can these ESG indices be replicated by benchmark counterparts? Do ESG equity indices enhance portfolio diversification? The findings reveal that investing in ESG indices has the potential to enhance risk-adjusted returns and portfolio diversification.

Research limitations/implications

While this study focuses on various LA economies, it’s important to note variations in currency and volatility.

Practical implications

For investors in LA, this study highlights the importance of considering ESG indices as part of their investment strategies. While not all ESG indices outperform conventional ones, some may improve diversification and risk-adjusted performance. Investors should carefully assess market-specific conditions and national factors when making investment decisions.

Originality/value

The primary contribution of this study is its focus on LA countries in the examination of diverse portfolios. The research provides valuable insights into the performance of ESG indices in this region compared to conventional benchmark indices. This approach addresses an important gap in the existing literature and offers a more comprehensive perspective on ESG investing and portfolio diversification.