bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining the Influence of Optimal Guideline-Directed Medical Therapy on Patient-Reported Outcomes in Adults With Heart Failure
Authors: Alonso Windy W. , Pozehl Bunny J. , Kupzyk Kevin A. , Lundgren Scott W. , Diederich Theresa
Published: December 2024

Background

Multidrug, guideline-directed medical therapy (GDMT) improves mortality and hospitalizations for heart failure (HF), but little is known about how optimization of multidrug GDMT influences patient-reported outcomes. Trials of single GDMT medications demonstrate improvements in patient-reported outcomes; however, the effect of the multidrug GDMT regimen on patient-reported outcomes is unclear.

Objective

The objective of this study is to determine how multidrug optimization during a multidisciplinary, advanced practice provider HF clinic impacted patient-reported symptoms and quality of life in adults with HF.

Methods

This retrospective cohort study examined patient-reported outcomes at baseline and 12 weeks during a multidrug GDMT optimization clinic for HF. Outcomes were compared across time and male and female sex. Quality of life was measured with the EQ5D. Symptoms were measured using the PROMIS-29 and PROMIS-Dyspnea Severity score. Descriptive statistics describe sample characteristics. Paired and independent t tests were used for comparisons.

Results

Of 301 adults with HF enrolled in a clinic, 101 completed patient-reported outcome measures at baseline and 12 weeks. Patients (predominantly White/Caucasian males; mean age, 59 years) reported significant improvement in the EQ5D domains of mobility and performance of usual activities, and PROMIS-29 subscales for physical function, fatigue, and ability to participate in social roles. Sex differences were noted for pain and depression, with females reporting improved pain and males reporting slightly less depression.

Conclusions

Multidisciplinary, advanced practice provider–led optimization clinics can promote optimization of multidrug GDMT that can improve patient-reported outcomes in adults with HF. Future studies are needed to comprehensively examine sex differences in patient-reported response to GDMT and patient-reported response to updated, “quadruple-therapy” GDMT recommendations.
Huddles in Hospital Maternity Settings
Authors: Bernstein Samantha L. , Bell Jessica G. , Broadhurst Rebecca
Published: December 2024

Background:

The Agency for Healthcare Research and Quality recommends the use of safety huddles, in which clinicians are briefly gathered to review a patient's condition, including new or developing changes in acuity or stability. The Joint Commission describes huddles as a “hallmark” of high-reliability organizations. Previous reviews have confirmed the general utility of huddles, including positive regard by clinicians, but there has not been work specifically looking at huddle use in hospital maternity care settings. Our objective was to identify the ways that huddles have been studied or reported in inpatient maternity settings and synthesize this information with recommendations from professional organizations to identify gaps in the literature published in the United States since 1999.

Methods:

We used Arksey and O'Malley's framework to guide our scoping review. Using the time frame from 1999 to 2024, we searched the following databases: PubMed, CINAHL, SCOPUS, Embase, as well as gray literature and the reference lists and citing articles of the included manuscripts.

Results:

We found 160 documents, of which 47 met inclusion criteria, including 11 care bundles, 10 quality improvement projects, and 4 research studies. The remaining 22 were a variety of editorials, position papers, and other gray literature.

Discussion:

There is scant research on the use of huddles in hospital maternity care settings, and most literature does not define the participants, timing, or agenda of the huddle. Further research is needed to understand how huddles affect outcomes in maternity settings. Researchers should explicitly define the huddles they are studying. The review protocol was registered at Open Science Framework Registries.
Application of Predictive Analytics in Pregnancy, Birth, and Postpartum Nursing Care
Authors: Dreisbach Caitlin , Barcelona Veronica , Turchioe Meghan Reading , Bernstein Samantha , Erickson Elise
Published: December 2024

Predictive analytics has emerged as a promising approach for improving reproductive health care and patient outcomes. During pregnancy and birth, the ability to accurately predict risks and complications could enable earlier interventions and reduce adverse events. However, there are challenges and ethical considerations for implementing predictive models in perinatal care settings. We introduce major concepts in predictive analytics and describe application of predictive modeling to perinatal care topics such as fertility, preeclampsia, labor onset, vaginal birth after cesarean, uterine rupture, induction outcomes, postpartum hemorrhage, and postpartum mood disorders. Although some predictive models have achieved adequate accuracy (AUC 0.7-0.9), most require additional external validation across diverse populations and practice settings. Bias, particularly racial bias, remains a key limitation of current models. Nurses and advanced practice nurses, including nurse practitioners certified registered nurse anesthetists, and nurse-midwives, play a vital role in ensuring high-quality data collection and communicating predictive model outputs to clinicians and users of the health care system. Addressing the ethical challenges and limitations of predictive analytics is imperative to equitably translate these tools to support patient-centered perinatal care.
Change of TMJ Space Volume After Mandibular Setback BSSRO With Intended Manual Condyle Positioning in Severe Facial Asymmetric Patients
Authors: Bae Jung-Hwan , Hwang Ji-Young , Lee Jae-Yeol , Hwang Dae-Seok
Published: December 2024

Purpose:

This study aimed to quantitatively analyze temporomandibular joint (TMJ) space volume changes before and after bilateral sagittal split ramus osteotomy (BSSRO) with intended manual condyle positioning in patients with severe facial asymmetry.

Methods:

A retrospective study was conducted, including 20 patients with facial asymmetry (menton deviation >8 mm) who underwent BSSRO with intended manual condyle positioning at a single institution. Cone beam computed tomography (CBCT) images were obtained preoperatively (T0), 2 days postoperatively (T1), and 6 months postoperatively (T2). TMJ space volumes on the deviation side (DS) and non deviation side (NDS) were measured at each time point. Changes in TMJ space volume were analyzed over time and compared between the DS and NDS using appropriate statistical methods.

Results:

Both the DS and NDS exhibited an increasing trend in TMJ space volume from T0 to T1, followed by a reduction at T2, approaching levels similar to T0. The change in volume from T0 to T1 was more pronounced on the DS compared with the NDS.

Conclusions:

In patients with severe facial asymmetry undergoing BSSRO, there is a tendency for the TMJ space to increase initially. However, incorporating manual condylar positioning to achieve a stable condyle position results in the TMJ space returning to pre-surgery levels by 6 months postoperatively. These findings suggest that intended manual condyle positioning may help maintain proper TMJ function following BSSRO in patients with severe facial asymmetry.
Survival Outcomes of 997 Patients With Eyelid Sebaceous Carcinoma in the National Cancer Database
Authors: Huck Nolan A. , Khosravi Pooya , Torabi Sina J. , Zhou Paul S. , Nguyen Theodore V. , Tao Jeremiah P. , Kuan Edward C. , Dermarkarian Christopher R.
Published: December 2024

Objectives:

This study aimed to characterize the survival of patients with sebaceous carcinoma (SC) of the eyelids according to demographics and other variables.

Methods:

Patients with SC of the eyelids from 2004 to 2017 were identified in the National Cancer Database. Demographic and clinical covariates were assessed. Univariate analysis and multivariate Cox proportional hazard models were employed for survival analysis.

Results:

A total of 997 of 1101 patients were included. Most patients were females (57.8%), white (88.7%), and presented in their seventh to ninth decade of life (62.5%). Surgical excision (89.2%) was the primary treatment. Older patients were likely to be females, located in the Midwest United States, and were likely to present with T3/4 staging (P < 0.01). Males were more likely to be younger (P < 0.01), black (P = 0.03), and located in the Southern United States (P = 0.05). Kaplan-Meier univariate analysis demonstrated: greater 3-year overall survival (OS) for patients younger than 60 years (95.0%) compared with patients aged 60 to 79 (88.8%) and aged older than 80 years (69.7%) (P < 0.01) and greater 3-year OS for patients with T1-2b staging (83.6%) compared with T3-4 staging (74.0%; P < 0.01). Multivariate Cox regression demonstrated males (P < 0.01), older age (P < 0.01), and M1+ staging (P < 0.01) had greater risk of death as determined by hazard ratios.

Conclusion:

Patients with SC of the eyelids were female, white, and older than 70 years of age. There was a significantly greater 3-year OS for patients who were <60 years of age and who had T1-2b staging. Multivariate analysis demonstrated males, older age, and metastases portend a higher risk of death.
KLF10 Induced by Hypothermic Machine Perfusion Alleviates Renal Inflammation Through BIRC2/Noncanonical NF-κB Pathway
Authors: Hu Qianchao , Chen Hao , Lan Jia’nan , Chen Yiwen , Liu Zhongzhong , Xiong Yan , Zhou Wei , Zhong Zibiao , Ye Qifa
Published: December 2024

Background.

Hypothermic machine perfusion (HMP) is becoming the main preservation method for donation after circulatory death (DCD) kidneys. It can provide continuous flow and form shear stress (SS) upon endothelial cells (ECs), thereby regulating EC injury. Krüppel-like factor 10 (KLF10) has been shown to lessen vascular damage. However, how SS and KLF10 impact HMP-regulated injury is unclear.

Methods.

In this study, we investigated the influences of KLF10 on HMP in animal models and human renal biopsy and explored how SS affected KLF10 expression in a parallel-plate flow chamber system. Chromatin Immunoprecipitation sequencing and luciferase assay were performed to seek the target genes of KLF10. The influences of KLF10 on HMP-regulated injury were investigated by transfecting si-KLF10 adeno-associated virus serotype 9 into rat kidneys. The molecular expression was examined using immunofluorescence staining, Western blotting, and quantitative polymerase chain reaction.

Results.

Our results show KLF10 expression was augmented in human, rabbit, and rat DCD kidneys after HMP. HMP improved ECs and tubule injury and attenuated inflammation; however, the knockdown of KLF10 reversed this effect. SS regulated KLF10 expression in ECs by affecting F-actin, and KLF10 could maintain ECs homeostasis. Chromatin Immunoprecipitation sequencing and luciferase assay revealed that baculoviral inhibitor of apoptosis protein repeat-containing 2 (BIRC2
) is a target gene of KLF10. Furthermore, BIRC2 linked to nuclear factor kappa B (NF-κB)-inducing kinase, induced NF-κB)-inducing kinase ubiquitination, and resulted in inhibiting the noncanonical NF-κB pathway.

Conclusions.

SS can mediate KLF10 expression, whereas HMP can protect against warm ischemic injury by reducing inflammation via KLF10/BIRC2/noncanonical NF-κB pathway. Therefore, KLF10 might be a novel target for improving DCD kidney quality.
Orbital angular momentum of single photons: revealing quantum fundamentals
Authors: Padgett Miles
Published: December 2024

In 1992, Allen
et al
. (Allen L, Beijersbergen MW, Spreeuw RJC, Woerdman JP. 1992 Orbital angular momentum of light and the transformation of Laguerre-Gaussian laser modes.
Phys. Rev. A
45
, 8185–8189. (
doi:10.1103/physreva.45.8185
)) published their seminal paper on the orbital angular momentum of light, drawing together seemingly unrelated themes and ideas in optics. This breakthrough initiated a new area of optical science concerning the physics and applications of structured light beams. This orbital angular momentum is an important concept for both classical and quantum science, especially where the framing in terms of angular momentum demystifies some of the quantum properties of light. Loudon’s own work (Loudon R. 2003 Theory of the forces exerted by Laguerre-Gaussian light beams on dielectrics.
Phys. Rev. A
68
, 013806. (
doi:10.1103/PhysRevA.68.013806
)) in this area focused on the interactions between light and matter where the orbital angular momentum extended his studies from linear impulses to rotational torques.

This article is part of the theme issue ‘The quantum theory of light’.
Generalizing multipartite concentratable entanglement for practical applications: mixed, qudit and optical states
Authors: Foulds Steph , Prove Oliver , Kendon Viv
Published: December 2024

The controlled SWAP test for detecting and quantifying entanglement applied to pure qubit states is robust to small errors in the states and efficient for large multi-qubit states (Foulds
et al
. 2021
Quantum Sci. Technol
.
6
, 035002 (doi:
10.1088/2058-9565/abe458
)). We extend this, and the related measure
concentratable entanglement
(CE), to enable important practical applications in quantum information processing. We investigate the lower bound of concentratable entanglement given in (Beckey
et al
. 2023
Phys. Rev. A
107
, 062425 (doi:
10.1103/physreva.107.062425
)) and conjecture an upper bound of the mixed-state concentratable entanglement that is robust to c-SWAP test errors. Since experimental states are always slightly mixed, our work makes the c-SWAP test and CE measure suitable for application in experiments to characterize entanglement. We further present the CE of some key higher-dimensional states such as qudit states and entangled optical states to validate the CE as a higher-dimensional measure of entanglement.

This article is part of the theme issue ‘The quantum theory of light’.
ABHD2 activity is not required for the non-genomic action of progesterone on human sperm
Authors: Arnolds Oliver , Carter Eve M. , Edwards Madison , Wigren Edvard , Homan Evert , Ribera Pauline , Bentley Kirsty , Haraldsson Martin , Theo-Emegano Nmesoma , Loppnau Peter , Szewczyk Magdalena M , Cao Michelle A , Barsyte-Lovejoy Dalia , Vester Karen , Thrun Anna , Amaral Alexandra , Lesche Ralf , Münchow Jens , Zhu W. Felix , Temme Louisa , Brenker Christoph , Strünker Timo , Sundström Michael , Todd Matthew H. , Edwards Aled M , Tredup Claudia , Gileadi Opher
Published: December 2024

Sperm activation is controlled by an influx of calcium ions through the CatSper channel, which is activated in the oviduct by a non-genomic action of progesterone. Progesterone has been hypothesized to act as an activator of ABHD2 activity, which in turn hydrolyses 1- and 2- arachadinoyl glycerol, putative inhibitors of CatSper. To explore the idea of targeting ABHD2 activity as a contraceptive target, we synthesized derivatives of published ABHD2 inhibitors, optimizing for potency and in-cell target engagement, and tested active inhibitors and structurally-related inactive derivatives in sperm motility assays and calcium influx assays. We observed no effect of ABHD2 inhibition on basal or progesterone-induced activity in both assays. We also found no evidence for direct binding of progesterone to purified recombinant ABHD2 protein. We conclude that ABHD2 activity is not required for the non-genomic action of progesterone on human sperm.
Missing what’s right under your nose: failed appetitive and aversive audio-olfactory conditioning in humans
Authors: Menger N.S. , Kotchoubey B. , Ohla K. , Pavlov Y.G.
Published: December 2024

The comparison of physiological mechanisms underlying appetitive and aversive conditioning is often challenging due to the involvement of stimuli from different modalities with potentially disparate effective mechanisms (e.g., pain stimuli versus monetary rewards). The olfactory system offers a unique opportunity to examine both types of conditioning in humans, as isointense odors can serve as comparably pleasant and unpleasant stimuli. To study physiological and behavioral responses during appetitive and aversive learning, we employed odors as unconditioned stimuli (US) in a within-subjects design, measuring various conditioned physiological responses including skin conductance, heart rate, pulse wave amplitude, respiration, fear-potentiated startle, postauricular reflex, facial electromyography as well as event-related potentials, and auditory steady-state responses (ASSR) derived from electroencephalography. We conducted four experiments with a total of 95 participants, presenting three neutral sounds paired with either a pleasant odor, unpleasant odor, or odorless air. The first experiment involved uninstructed participants and frequency-modulated conditioned stimuli (CS) for ASSR analysis. In the second experiment, we omitted the frequency modulation and startle probe. The third experiment included pre-experiment instruction on CS-US contingencies, while the fourth employed a delayed conditioning paradigm in contrast to the other three experiments. Our results revealed differences between CS+ and CS-only in the fear-potentiated startle response in Experiment 3. No other effects were found. The minimal or absent learning effects observed across multiple peripheral and neural physiological measures may be attributed to the extra-thalamic nature of olfactory pathways and the subsequent difficulty in forming associations with auditory stimuli.

Impact statement

In a series of 4 experiments, we explored the neurophysiological differences between appetitive and aversive conditioning. Yet, none of the experiments showed effective conditioning. We hypothesize that the lack of learning effects is attributed to the inherent difficulty in forming associations between auditory and olfactory inputs.
The perceptions and roles of teachers and caregivers on play in promoting children’s early learning and development in a rural Kenya
Authors: Otwate Paul , Nampijja Margaret , Langat Nelson , Oloo Linda , Onyango Silas , Mabongah Jesse , Makhapila Erick , Ooko Silas , Odhiambo Brian , Kitsao-Wekulo Patricia
Published: December 2024

Adults, including teachers and parents have an important role in supporting children’s learning and development through play. This paper aimed to explore parents’ and teachers’ viewpoints and roles on play in promoting early learning and development in children, which has little emphasis in existing studies. This paper employed a cross-sectional study using a mixed-method approach to gather data from preschool teachers (n=96), parents (n=126), and policy implementers (n=6) in Kenya. We used questionnaires, focus group discussions, and interview guides to collect qualitative and quantitative data through face-to-face interviews with teachers and parents and mobile interviews with policy stakeholders. We performed qualitative analysis through reviewing the study transcripts, coding, and generating emerging themes that later guided the draft of the narrative report. Quantitative data were coded, cleaned, and reviewed before they were descriptively computed on the Stata version 18 to generate graphic representations. Our findings revealed that teachers and parents jointly perceived play to be pivotal on children’s learning and development. In addition, parents and teachers recognized that it is their role to engage children in play, provide play materials, and supervise children. Based on our results, we suggest that preschool teachers and parents collaboratively identify days to jointly develop play materials in preschool centers. This strategy may present a better understanding of the adults’ primary role of facilitating play and play-based learning. Our findings may serve as a resource and source of information for preschool teachers, parents, and policy stakeholders to consider play not only as a development pathway but also an element of learning and contributor to school readiness in children.
Prevalence and predictors of anemia in children under 5 years of age in sub-Saharan Africa: a systematic review and meta-analysis
Authors: Gotine Ana Raquel Ernesto Manuel , Xavier Sancho Pedro , Vasco Melsequisete Daniel , Alfane Nerys Wendy Antonieta , Victor Audêncio
Published: December 2024

Background

Anemia is a significant public health challenge in Sub-Saharan Africa, particularly affecting children under five years old and posing serious health and developmental consequences. This systematic review and meta-analysis aim to quantify the prevalence and identify the predictors of anemia in this vulnerable age group across the region.

Methods

A systematic review and meta-analysis were conducted in adherence to PRISMA guidelines. Observational studies reporting on the prevalence and predictors of anemia among children under five in Sub-Saharan Africa were included. Comprehensive searches were performed in PubMed, Scopus, Web of Science, and Embase databases. The Joanna Briggs Institute (JBI) tools were used for critical appraisal. A random-effects model was applied to estimate pooled prevalence, while heterogeneity and publication bias were assessed using R software.

Results

A total of 32 studies comprising 93,388 children were included. The pooled prevalence of anemia was 55%, reflecting a widespread public health issue, with significant heterogeneity (I² = 99.7%). Key predictors included younger age (particularly 0–23 months), male gender, and indicators of poor nutritional status such as stunting. Socioeconomic and environmental factors, including rural residency and low maternal education, were also strongly associated with higher anemia rates. The observed variability across studies highlights the multifaceted nature of anemia’s determinants in the region.

Conclusion

The consistently high prevalence of anemia among children under five in Sub-Saharan Africa underscores the need for integrated public health strategies. Efforts to address nutritional deficiencies, improve maternal education, and enhance living conditions are essential to mitigate the burden of anemia and improve child health outcomes in the region.
Phylogenetic relatedness rather than aquatic habitat fosters horizontal transfer of transposable elements in animals
Authors: Muller Héloïse , Savisaar Rosina , Peccoud Jean , Charlat Sylvain , Gilbert Clément
Published: December 2024

Horizontal transfer of transposable elements (HTT) is an important driver of genome evolution, yet the factors conditioning this phenomenon remain poorly characterized. Here, we screened 247 animal genomes from four phyla (annelids, arthropods, mollusks, chordates), spanning 19 independent transitions between aquatic and terrestrial lifestyles, to evaluate the suspected positive effects of aquatic habitat and of phylogenetic relatedness on HTT. Among the 5,952 independent HTT events recovered, the vast majority (>85%) involve DNA transposons, of which Mariner-like and hAT-like elements have the highest rates of horizontal transfer, and of intra-genomic amplification. Using a novel approach that circumvents putative biases linked to phylogenetic inertia and taxon sampling, we found that HTT rates positively correlate with similarity in habitat type but were not significantly higher in aquatic than in terrestrial animals. However, modelling the number of HTT events as a function of divergence time in a Bayesian framework revealed a clear positive effect of phylogenetic relatedness on HTT rates in most of the animal species studied (162 out of 247). The effect is very pronounced: a typical species is expected to show 10 times more transfers with a species it diverged from 125 million years (My) ago than with a species it diverged from 375 My ago. Overall, our study underscores the pervasiveness of HTT throughout animals and the impact of evolutionary relatedness on its dynamics.

Significance statement

Genetic material can be transmitted between organisms through other means than reproduction, in a process called horizontal transfer. The mechanisms and factors underlying this phenomenon in animals remain unclear, although it often involves transposable elements (TEs). TEs are DNA segments capable of jumping within genomes, but also occasionally between individuals. Here, we show evidence for nearly 6,000 transfers of TEs among animals, based on genomic comparisons among 247 species of annelids, arthropods, chordates and mollusks. Contrarily to expectations, we found no excess in the rates of transfers in aquaticversusterrestrial animals. By contrast, most analyzed species appeared engaged in many more horizontal transfers with close than with distant relatives, highlighting the strong impact of phylogenetic relatedness on horizontal transfers of TEs.
Learning the Language of Phylogeny with MSA Transformer
Authors: Chen Ruyi , Foley Gabriel , Bodén Mikael
Published: December 2024

Classical phylogenetic inference assumes independence between sites, potentially undermining the accuracy of evolutionary analyses in the presence of epistasis. Some protein language models have the capacity to encode dependencies between sites in conserved structural and functional domains across the protein universe. We employ the MSA Transformer, which takes a multiple sequence alignment (MSA) as an input, and is trained with masked language modeling objectives, to investigate if and how effects of epistasis can be captured to enhance the analysis of phylogenetic relationships.

We test whether the MSA Transformer internally encodes evolutionary distances between the sequences in the MSA despite this information not being explicitly available during training. We investigate the model’s reliance on information available in columns as opposed to rows in the MSA, by systematically shuffling sequence content. We then use MSA Transformer on both natural and simulated MSAs to reconstruct entire phylogenetic trees with implied ancestral branchpoints, and assess their consistency with trees from maximum likelihood inference.

We demonstrate how both previously known and novel evolutionary relationships are available from a “non-classical” approach with very different computational requirements, by reconstructing phylogenetic trees for the RNA virus RNAdependent RNA polymerase and the nucleo-cytoplasmic large DNA virus domain. We anticipate that MSA Transformer will not replace but rather complement classical phylogenetic inference, to accurately recover the evolutionary history of protein families.
Risk assessment of zoonotic viruses in urban-adapted wildlife
Authors: Wei Xuemin , Li Hongfeng , Huang Zheng Y.X. , Li Shuo , Wang Yuhao , Lan Jie , Hu Li , Li Yang , Becker Daniel J. , Wei Fuwen , Xu Yifei
Published: December 2024

The repeated emergence of pandemic viruses underscores the linkages between land-use change and wildlife disease, and urban-adapted wildlife are of special interest due to their close proximity to humans. However, viral diversity within urban-adapted species and their zoonotic potential remains largely unexplored. We compiled a large dataset on seven priority urban-adapted mammal species and their viruses covering over 115 countries from 1574 to 2023. These urban-adapted species host 286 virus species spanning 24 orders and 38 families, 14 of which are potentially high risk for human infection. Raccoons carried the most high-risk viruses, while raccoon dogs had increased viral positivity in urban habitats compared to raccoons, wild boars, and red foxes. Many viruses in urban-adapted species were phylogenetically related to those found in humans, and we also observed evidence of possible viral spillback. These results highlight zoonotic risks associated with urban-adapted species and suggest enhanced surveillance to mitigate future outbreaks.
Benchmarking scRNA-seq copy number variation callers
Authors: Schmid Katharina T. , Symeonidi Aikaterini , Hlushchenko Dmytro , Richter Maria L. , Colomé-Tatché Maria
Published: December 2024

Copy number variations (CNVs), the gain or loss of genomic regions, are associated with different diseases and cancer types, where they are related to tumor progression and treatment outcome. Single cell technologies offer new possibilities to measure CNVs in individual cells, allowing to assess population heterogeneity and to delineate subclonal structures. Single cell whole-genome sequencing is considered the gold-standard for the quantification of CNVs in single cells. However, the majority of existing single cell datasets interrogate gene expression, using scRNA-seq. Consequently, several computational approaches have been developed to identify CNVs from that data modality. Nevertheless, an independent benchmarking of these methods is lacking. We used 15 scRNA-seq datasets and evaluated six popular computational methods in their ability to recover the ground truth CNVs using a large set of performance metrics. Additionally, we explored whether they could correctly identify euploid cells, especially also in fully diploid samples, and subclonal structures in heterogeneous tumor samples. We discovered several dataset-specific factors that influence the performance of the methods, such as the dataset size and the number and type of CNVs in the analyzed sample. We found that the choice of the reference dataset can have a large impact on the performance. Methods which included additional allelic information from the scRNA-seq reads performed more robustly across scenarios, but at the cost of higher runtime. Furthermore, the methods differed substantially in their additional functionalities and resource requirements. We offer a benchmarking pipeline to help identify the optimal CNV calling method for newly generated scRNA-seq datasets, and to benchmark and improve new methods performance.
I2SIM: Boosting High-Fidelity Isotropic Super-Resolution with Image Interference and Spatial-Spectral Optimization
Authors: He Enxing , Sun Yile , Zhu Hongfei , Yang Xinxun , Yin Lu , Han Yubing , Kuang Cuifang , Liu Xu
Published: December 2024

Spatial resolution is crucial for imaging subcellular structures. The advent of three-dimensional structured illumination microscopy (3D-SIM) greatly benefits the biology community, providing a powerful tool for imaging organelles with a two-fold resolution enhancement in all three dimensions. However, the axial resolution of 3D-SIM is limited to around 300 nm, which is inferior to its lateral resolution. Here, a novel method called image interference SIM (I2SIM) is reported, which utilizes two oppositely positioned objectives to detect fluorescence emission interference under three-beam excitation. By incorporating spectral modulation and spatial domain Frobenius-Hessian optimization, I2SIM achieves an axial resolution approximately twice that of 3D-SIM, reaching around 130 nm. Furthermore, the potential of I2SIM for imaging subcellular structures is demonstrated on various biological samples, including microtubules, actin filaments, and mitochondrial outer membranes. The enhanced optical sectioning capability can be utilized to resolve axial structures that are challenging to discern using ordinary 3D-SIM.
Incidence of acute ischemic stroke after COVID-19 or influenza among older adults, findings from PCORnet and HealthVerity, 2022
Authors: Koumans Emilia H. , Raykin Julia , Boehmer Tegan K. , Saydah Sharon , Wiltz Jennifer , Garg Shikha , DeSantis Carol E. , Carton Thomas W. , Cowell Lindsay G. , Thacker Deepika , Arnold Jonathan , Rasmussen Sonja A. , Smith Samantha J. , Barrett Kimberly , Draper Christine , Coronado Fátima , Lundeen Elizabeth A. , Woodruff Rebecca C. , Block Jason P.
Published: December 2024

Background

Although COVID-19 is a known risk factor for thrombotic conditions including embolism, stroke, and myocardial infarction, stroke incidence after implementation of thromboprophylaxis during COVID-19 hospitalization in 2021 and how incidence may differ from influenza is unknown.

Methods

PCORnet and HealthVerity (HV) data assets were used to identify patients aged ≥65 years with no prior stroke and COVID-19 or influenza during January 1-December 31, 2022, and AIS from 3 days before to 28 days after COVID-19 or influenza diagnosis. Overall demographic information (age [for HV], sex, race/ethnicity), underlying conditions, level of care, outcomes, and incidence were described and compared between those with early (-3 to 7 days from diagnosis date) and late (8 to 28 days) AIS.

Results

Among 245,352 (PC) and 639,396 (HV) patients aged ≥65 years with COVID-19, the incidence of ischemic stroke in the 3 days prior to 7 days after diagnosis of COVID-19 (PC: 962/100,000 and HV: 447/100,000) and influenza (PC: 589/100,000 and HV: 387/100,000) was significantly higher than in the 8 to 28 days after diagnosis (COVID PC: 81/100,000 and HV: 141/100,000)(influenza PC:75/100,000 and HV: 15/100,000)(all P<0.01).

Conclusions

Continued risk for AIS with acute COVID-19 and influenza underscore the importance of monitoring and prevention measures for older adults.
Cadmium and Lead Attributable Burden of Cancers in Skipjack (Katsuwonus pelamis) and Yellowfin (Thunnus albacares) in Ghana
Authors: Nkansah J. A. , Lutterodt H.E. , Dodoo A. , Ofosu I.W.
Published: December 2024

Toxic heavy metal contamination in fish sources poses significant health risks, particularly in populations that rely on fish as a primary dietary component. Thus, this study aimed to assess the concentrations of cadmium (Cd) and lead (Pb) in selected tuna species and evaluate the associated health risks and cancer burdens to consumers in Ghana through a systematic review and meta-analysis of data covering the period 2015 to 2019. A Disability Adjusted Life Year (DALY) approach was used to quantify the health burden with secondary data from the Institute of Health Metrics and Evaluation (IHME). Median contaminant exposure was 1.26 × 10-5mg/kg(bw)-day for Cd, and 1.04 × 10-4mg/kg(bw)-day for Pb. The highest DALY was found in the elderly age group (55-89) and it ranged from 10-5- 10-3. The results indicate that in the elderly age group, stomach cancer was the most prevalent for both males and females, reflecting a significant cancer burden. For elderly males, prostate cancer was also a severe concern, contributing to the overall cancer burden, although its prevalence was lower than that of stomach cancer. In elderly females, however, pancreatic cancer was observed to have a higher prevalence compared to males, indicating gender-specific differences in cancer risk among older adults. The findings underscore the need for public health interventions to mitigate the risks of heavy metal contamination in fish.
Comparative analysis of dietary iron deprivation and supplementation in a murine model of colitis
Authors: Medjbeur Thanina , Sardo Ugo , Perrier Prunelle , Cormier Kevin , Roy Marilyne , Dumay Anne , Kautz Léon
Published: December 2024

Inflammatory bowel diseases are chronic inflammatory conditions with growing prevalence in western populations. Iron is an essential component of erythrocytes hemoglobin. Under the influence of elevated hepcidin production, iron is sequestered in cells during inflammation which, in turn, leads to iron restriction for red blood cells synthesis. As a consequence, iron deficiency and anemia of inflammation are the most prevalent extraintestinal complications in IBD patients. Patients are thus treated with oral iron supplements that have limited efficacy as iron absorption is blunted during intestinal inflammation. Moreover, iron supplementation can cause intestinal complications and previous studies have shown that iron supplementation worsens the inflammatory response. However, a comparative analysis of the effects of low, adequate and high dietary iron content matching iron the supplementation given to patients has not been performed in mice. We therefore tested the impact of dietary iron deprivation and supplementation in a murine model of colitis induced by dextran sodium sulfate. We found that both dietary iron deprivation and supplementation were accompanied by a more severe inflammation with earlier signs of gastrointestinal bleeding compared to mice fed an iron adequate diet. The manipulation of dietary iron led to a comparable oxidative stress and a pronounced dysbiosis in the colon of control mice that differed depending on the dietary iron content. Analysis of these dysbiosis is in line with a pronounced susceptibility to colonic inflammation thus questioning the benefit/risk balance of oral iron supplementation for IBD patients.
Transcriptomic disruption and functional hypoactivity in DYT-SGCEMGE-patterned inhibitory neurons
Authors: Li Zongze , Abram Laura , Cruz-Santos Maria , Petter Olena , Peall Kathryn J
Published: December 2024

Myoclonus Dystonia is a dystonic movement disorder caused bySGCEmutations, the underlying pathophysiology for which remains unclear. Here, we evaluated the impact ofSGCEmutations on medial ganglionic eminence (MGE)-derived GABAergic neurons using patient-derived induced pluripotent and gene edited embryonic stem cell lines, each compared to their isogenic wild-type control. No significant differences were observed in markers of neuronal development however, single-cell RNA sequencing demonstrated transcriptomic dysregulation in genes related to axonal organization, synaptic signalling, and action potential generation in theSGCE-mutation harbouring neurons. Functional assays demonstrated reduced neurite outgrowth, lower calcium responses to GABA, and decreased neuronal excitability and network activity in theSGCE-mutant neurons. These findings contrast with the hyperexcitable phenotype previously observed inSGCE-mutant cortical glutamatergic neurons. Collectively, this supports loss of neuronal inhibitory activity, and disruption to the neuronal excitatory/inhibitory balance in motor circuits, in contributing to the overall hyperkinetic clinical phenotype in Myoclonus Dystonia.
NURSING PHILOSOPHY OF FAMILY SUPPORT FOR PATIENT CARE SKIZOFRENIA: A LITERATURE REVIEW
Authors: Halawa Aristina , Yusuf Ah. , Rumambo Pandin Moses Glorino
Published: December 2024

Introduction

The emergence of deinstitutionalisation of people with mental disorders has led to the burden of patient care being shifted to families. Patients with schizophrenic disorders who live with their families account for up to 50%. Families play an important role in the lives of individuals living with mental illnesses such as schizophrenia. Caregivers often face economic burdens and challenges in managing daily household tasks, which can exacerbate stress and reduce their overall well-being. This family support is lacking as family caregivers often experience significant emotional and physical stress due to the high demands of caregiving. If an individual receives emotional, informational, or instrumental support from their family then they will likely have greater confidence, hope, and optimism to pursue recovery and live a fulfilling and meaningful life.

Methods

This research uses a literature review using the PICOS framework. The literature for the originality of this research uses articles in English from 4 databases: Science direct, Scopus, Sage and EBSCOhost. The keywords used in the literature search were: “family support” AND family AND support AND schizophrenia. The search was limited to publications from 2019-2024 and the articles retrieved were full articles not review articles. The strategy used to search for articles used the PICOS framework. Then selected using PRISMA diagram and obtained ten articles.

Results

There are 10 articles obtained and all of them explain about family support in caring for schizophrenia patients both from factors that affect family support, forms of family support and the impact of family support on caregivers or family members and patients. Thus, family support is very important for the welfare of caregivers and for patients who experience schizophrenia disorders.

Conclusion

Family support is essential in the care of patients with schizophrenia. There are several barriers that prevent families from accessing necessary resources and support, including stigma, lack of information, and limited contact with the healthcare team. Family Support provided to caregivers as well as to patients provides better outcomes for patients including increased independence and improved daily functioning, reduced caregiver burden and improved caregiver ability to provide care.
Diazepam modulates hippocampal CA1 functional connectivity in people at clinical high-risk for psychosis
Authors: Livingston Nicholas R. , Kiemes Amanda , O’Daly Owen , Knight Samuel R. , Lukow Paulina B. , Jelen Luke A. , Reilly Thomas J. , Dima Aikaterini , Nettis Maria Antonietta , Casetta Cecilia , Devenyi Gabriel A. , Spencer Thomas , De Micheli Andrea , Fusar-Poli Paolo , Grace Anthony A. , Williams Steve C.R. , McGuire Philip , Chakravarty M. Mallar , Egerton Alice , Modinos Gemma
Published: December 2024

Background

Preclinical evidence suggests that diazepam enhances hippocampal γ-aminobutyric acid (GABA) signalling and normalises a psychosis-relevant cortico-limbic-striatal circuit. Hippocampal network dysconnectivity, particularly from the CA1 subfield, is evident in people at clinical high-risk for psychosis (CHR-P), representing a potential treatment target. This study aimed to forward-translate this preclinical evidence.

Methods

In this randomised, double-blind, placebo-controlled study, 18 CHR-P individuals underwent resting-state functional magnetic resonance imaging twice, once following a 5mg dose of diazepam and once following a placebo. They were compared to 20 healthy controls (HC) who did not receive diazepam/placebo. Functional connectivity (FC) between the hippocampal CA1 subfield and the nucleus accumbens (NAc), amygdala, and ventromedial prefrontal cortex (vmPFC) was calculated. Mixed-effects models investigated the effect of group (CHR-P placebo/diazepam vs. HC) and condition (CHR-P diazepam vs. placebo) on CA1-to-region FC.

Results

In the placebo condition, CHR-P individuals showed significantly lower CA1-vmPFC (Z=3.17,PFWE=0.002) and CA1-NAc (Z=2.94,PFWE=0.005) FC compared to HC. In the diazepam compared to placebo condition, CA1-vmPFC FC was significantly increased (Z=4.13,PFWE=0.008) in CHR-P individuals, and both CA1-vmPFC and CA1-NAc FC were normalised to HC levels. In contrast, compared to HC, CA1-amygdala FC was significantly lower contralaterally and higher ipsilaterally in CHR-P individuals in both the placebo and diazepam conditions (lower: placeboZ=3.46,PFWE=0.002, diazepamZ=3.33,PFWE=0.003; higher: placeboZ=4.48,PFWE<0.001, diazepamZ=4.22,PFWE<0.001).

Conclusions

This study demonstrates that diazepam can partially restore hippocampal CA1 dysconnectivity in CHR-P individuals, suggesting that modulation of GABAergic function might be useful in the treatment of this clinical group.
Minority populations exhibit distinct clinical and genetic features of celiac disease in the United States
Authors: Karnati Hemanth , Ying Wenjing , Long Xin , Touma Mary-Joe , Smith Ioana , Lewis Suzanne , Xing Chao , Burstein Ezra , Bolze Alexandre , Green Peter HR , Alkalay Michele J. , Kong Xiao-Fei
Published: December 2024

Celiac disease (CeD) is a heterogeneous autoimmune disorder influenced by genetic, environmental, and socioeconomic factors. However, little is known about clinical manifestations and genetic risks in minority populations. Using data from theAll of UsResearch Program, we analyzed 3,040 CeD patients, referred to as the AoU-CeD cohort, to identify clinical and genetic differences across racial and ethnic groups in the United States. CeD prevalence was highest among White individuals (1.08%) and significantly lower among Hispanic (0.36%) and Black (0.16%) populations. The majority of CeD patients were female (78.4%) and diagnosed between the ages of 18 and 64. Minority groups reported poorer physical and mental quality of life (QoL) and higher levels of pain. Ancestry-specific patterns emerged in CeD-associated conditions, with minorities more likely to report diarrhea and non-infectious gastroenteritis but less likely to have osteoporosis, hypothyroidism, chronic fatigue, or a family history of CeD. Compared to previously reported data showing that over 90% of CeD patients carry the HLA-DQ2.5 haplotype, genetic analysis revealed that only 49% of patients in the AoU-CeD cohort carried the high-risk HLA-DQ2.5 haplotype. Additionally, 16.5% lacked known HLA-DQ risk haplotypes, suggesting potential diagnostic or reporting inaccuracies. Minority groups exhibited higher rates of atypical symptoms, lower frequencies of the DQ2.5 haplotype, and distinct distributions of HLA-DQ genotypes. A long haplotype block spanning HLA-A1, B8, C7 and HLA-DQ2.5 was found in Europeans but absent in other ancestries. A genome-wide association study (GWAS) using over 11 million variants from whole-genome sequencing data identified 1,651 significant single-nucleotide polymorphisms (SNPs), primarily within the MHC locus, with the strongest signals observed predominantly among individuals of European ancestry. A predictive model incorporating HLA-DQ genotype, family history, and clinical features achieved 83% accuracy for identifying seropositive CeD. These results highlight the importance of ancestry-specific clinical presentations and genetic features in CeD.
Genomic Specificity of Anti-TCR mAbs determined by single-cell RNAseq
Authors: Magill Ian , Piekarsa Val , Kossida Sofia , Croteau Josh , Lee Amy , Balderas Robert , Zemmour David , Benoist Christophe ,   the immgenT Project
Published: December 2024

T cells play a pivotal role in the immune system, relying on their somatically rearranged T cell receptor (TCR) to recognize peptide-MHC complexes. A comprehensive and extensively used set of monoclonal antibodies (mAbs) against TCR Variable regions was generated in the previous century. The separate identification of mAb-specific TCR-V proteins andTRVgenes has resulted in multiple nomenclatures, making their relationships unclear. To formally re-establish this link and determine patterns of reactivity withinTRVsubfamilies, we sorted T cells positive for any one of a panel of 22 anti-V mAbs and determined theirTRVgenes by single-cell TCRseq. RNAseq data revealed consistently higher expression of repeated elements from the ERV1-family LTR RLTR6Mm (mapping toGm20400) in cells utilizingTRBVsegments encoded within a 66kb genomic region betweenTRBV23andTRBV30. Our findings provide a comprehensive resource for anti-TCR mAb specificity and insight into V-gene usage biases and T cell function.
Characterizing psilocybin as an antidepressant for adolescence in male and female rats
Authors: García-Cabrerizo Rubén , Beruete-Fresnillo Itziar , García-Fuster M. Julia
Published: December 2024

Adolescent depression is a significant public health concern, yet treatment options remain limited, particularly due to age- and sex-related differences in antidepressant efficacy. This study explored the rapid and long-lasting antidepressant-like potential of psilocybin in adolescent Sprague-Dawley rats, examining acute and repeated oral dosing effects while incorporating sex as a biological variable. An acute administration of psilocybin produced rapid antidepressant-like effects 30 minutes post-treatment in both male and female rats, demonstrated by reduced immobility and increased escape-related behaviour in the forced swim test. However, repeated daily administrations over 7 days revealed notable sex differences. In males, the antidepressant-like effects were sustained, at least, for up to 15 days post-treatment at both tested doses. In contrast, in females, the effects were dose-dependent and less enduring, persisting only up to 8 days at the highest dose tested. To the best of our knowledge, these results are the first ones to underscore psilocybin’s potential as a fast-acting and long-lasting antidepressant during adolescence, a developmental stage marked by high vulnerability to depression and reduced response to conventional treatments, while also emphasizing the importance of tailoring therapeutic approaches to individual biological factors such as sex.