bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional annotation of the animal genomes: An integrated annotation resource for the horse
Authors: Peng Sichong , Dahlgren Anna R. , Donnelly Callum G. , Hales Erin N. , Petersen Jessica L. , Bellone Rebecca R. , Kalbfleisch Ted , Finno Carrie J.
Published: March 2023

The genomic sequence of the horse has been available since 2009, providing critical resources for discovering important genomic variants regarding both animal health and population structures. However, to fully understand the functional implications of these variants, detailed annotation of the horse genome is required. Due to the limited availability of functional data for the equine genome, as well as the technical limitations of short-read RNA-seq, existing annotation of the equine genome contains limited information about important aspects of gene regulation, such as alternate isoforms and regulatory elements, which are either not transcribed or transcribed at a very low level. To solve above problems, the Functional Annotation of the Animal Genomes (FAANG) project proposed a systemic approach to tissue collection, phenotyping, and data generation, adopting the blueprint laid out by the Encyclopedia of DNA Elements (ENCODE) project. Here we detail the first comprehensive overview of gene expression and regulation in the horse, presenting 39,625 novel transcripts, 84,613 candidate cis-regulatory elements (CRE) and their target genes, 332,115 open chromatin regions genome wide across a diverse set of tissues. We showed substantial concordance between chromatin accessibility, chromatin states in different genic features and gene expression. This comprehensive and expanded set of genomics resources will provide the equine research community ample opportunities for studies of complex traits in the horse.
SRGP-1/srGAP and AFD-1/afadin stabilize HMP-1/⍺-catenin at rosettes to seal internalization sites following gastrulation in C. elegans
Authors: Serre Joel M. , Slabodnick Mark M. , Goldstein Bob , Hardin Jeff
Published: March 2023

A hallmark of gastrulation is the establishment of germ layers by internalization of cells initially on the exterior. InC.elegansthe end of gastrulation is marked by the closure of the ventral cleft, a structure formed as cells internalize during gastrulation, and the subsequent rearrangement of adjacent neuroblasts that remain on the surface. We found that a nonsense allele ofsrgp-1/srGAPleads to 10–15% cleft closure failure. Deletion of the SRGP-1/srGAP C-terminal domain led to a comparable rate of cleft closure failure, whereas deletion of the N-terminal F-BAR region resulted in milder defects. Loss of the SRGP-1/srGAP C-terminus or F-BAR domain results in defects in rosette formation and defective clustering of HMP-1/⍺-catenin in surface cells during cleft closure. A mutant form of HMP-1/⍺-catenin with an open M domain can suppress cleft closure defects insrgp-1mutant backgrounds, suggesting that this mutation acts as a gain-of-function allele. Since SRGP-1 binding to HMP-1/⍺-catenin is not favored in this case, we sought another HMP-1 interactor that might be recruited when HMP-1/⍺-catenin is constitutively open. A good candidate is AFD-1/afadin, which genetically interacts with cadherin-based adhesion later during embryonic elongation. AFD-1/afadin is prominently expressed at the vertex of neuroblast rosettes in wildtype, and depletion of AFD-1/afadin increases cleft closure defects insrgp-1/srGAPandhmp-1R551/554A/⍺-cateninbackgrounds. We propose that SRGP-1/srGAP promotes nascent junction formation in rosettes; as junctions mature and sustain higher levels of tension, the M domain of HMP-1/⍺-catenin opens, allowing maturing junctions to transition from recruitment of SRGP-1/srGAP to AFD-1/afadin. Our work identifies new roles for ⍺-catenin interactors during a process crucial to metazoan development.
The anatomy of transcriptionally active chromatin loops in Drosophila primary spermatocytes using super-resolution microscopy
Authors: Ball Madeleine L. , Koestler Stefan A. , Muresan Leila , Rehman Sohaib Abdul , O’Holleran Kevin , White Robert
Published: March 2023

While the biochemistry of gene transcription has been well studied, our understanding of how this process is organised in 3D within the intact nucleus is less well understood. Here we investigate the structure of actively transcribed chromatin and the architecture of its interaction with active RNA polymerase. For this analysis, we have used super-resolution microscopy to image theDrosophila melanogasterY loops which represent huge, several megabases long, single transcription units. The Y loops provide a particularly amenable model system for transcriptionally active chromatin. We find that, although these transcribed loops are decondensed they are not organised as extended 10nm fibres, but rather they largely consist of chains of nucleosome clusters. The average width of each cluster is around 50nm. We find that foci of active RNA polymerase are generally located off the main fibre axis on the periphery of the nucleosome clusters. Foci of RNA polymerase and nascent transcripts are distributed around the Y loops rather than being clustered in individual transcription factories. However, as the RNA polymerase foci are considerably less prevalent than the nucleosome clusters, the organisation of this active chromatin into chains of nucleosome clusters is unlikely to be determined by the activity of the polymerases transcribing the Y loops. These results provide a foundation for understanding the topological relationship between chromatin and the process of gene transcription.
Self-organized metabotyping of obese individuals identifies clusters responding differently to bariatric surgery
Authors: Lappa Dimitra , Meijnikman Abraham S. , Krautkramer Kimberly A. , Olsson Lisa M. , Aydin Ömrüm , Van Rijswijk Anne-Sophie , Acherman Yair I. Z. , De Brauw Maurits L. , Tremaroli Valentina , Olofsson Louise E. , Lundqvist Annika , Hjorth Siv A. , Ji Boyang , Gerdes Victor E. A. , Groen Albert K. , Schwartz Thue W. , Nieuwdorp Max , Bäckhed Fredrik , Nielsen Jens
Published: March 2023

Weight loss through bariatric surgery is efficient for treatment or prevention of obesity related diseases such as type 2 diabetes and cardiovascular disease. Long term weight loss response does, however, vary among patients undergoing surgery. Thus, it is difficult to identify predictive markers while most obese individuals have one or more comorbidities. To overcome such challenges, an in-depth multiple omics analyses including fasting peripheral plasma metabolome, fecal metagenome as well as liver, jejunum, and adipose tissue transcriptome were performed for 106 individuals undergoing bariatric surgery. Machine leaning was applied to explore the metabolic differences in individuals and evaluate if metabolism-based patients’ stratification is related to their weight loss responses to bariatric surgery. Using Self-Organizing Maps (SOMs) to analyze the plasma metabolome, we identified five distinct metabotypes, which were differentially enriched for KEGG pathways related to immune functions, fatty acid metabolism, protein-signaling, and obesity pathogenesis. The gut metagenome of the most heavily medicated metabotypes, treated simultaneously for multiple cardiometabolic comorbidities, was significantly enriched in Prevotella and Lactobacillus species. This unbiased stratification into SOM-defined metabotypes identified signatures for each metabolic phenotype and we found that the different metabotypes respond differently to bariatric surgery in terms of weight loss after 12 months. An integrative framework that utilizes SOMs and omics integration was developed for stratifying a heterogeneous bariatric surgery cohort. The multiple omics datasets described in this study reveal that the metabotypes are characterized by a concrete metabolic status and different responses in weight loss and adipose tissue reduction over time. Our study thus opens a path to enable patient stratification and hereby allow for improved clinical treatments.
Seeking and receiving help for mental health services among pregnant women in Ghana
Authors: Adjorlolo Samuel
Published: March 2023

Objective

The heightened vulnerability of women to mental health issues during the period of pregnancy implies that seeking and receiving support for mental health services is a crucial factor in improving the emotional and mental well-being of pregnant women. The current study investigates the prevalence and correlates of seeking and receiving help for mental health services initiated by pregnant women and health professionals during pregnancy.

Design

Using a cross-sectional design and self-report questionnaires, data were collected from 702 pregnant women in the first, second and third trimesters from four health facilities in the Greater Accra region of Ghana. Data were analyzed using descriptive and inferential statistics.

Results

It was observed that 18.9% of pregnant women self-initiated help-seeking for mental health services whereas 64.8% reported that health professionals asked about their mental well-being, of which 67.7% were offered mental health support by health professionals. Diagnosis of medical conditions in pregnancy (i.e., hypertension and diabetes), partner abuse, low social support, sleep difficulty and suicidal ideation significantly predicted the initiation of help-seeking for mental health services by pregnant women. Fear of vaginal delivery and COVID-19 concerns predicted the provision of mental health support to pregnant women by health professionals.

Conclusion

The low prevalence of individual-initiated help-seeking implies that health professionals have a high responsibility of supporting pregnant women achieve their mental health needs.
Self-cleaving peptides for expression of multiple genes in Dictyostelium discoideum
Authors: Zhu Xinwen , Ricci-Tam Chiara , Hager Emily R. , Sgro Allyson E.
Published: March 2023

The social amoebaDictyostelium discoideumis a model for a wide range of biological processes including chemotaxis, cell-cell communication, phagocytosis, and development. Interrogating these processes with modern genetic tools often requires the expression of multiple transgenes. While it is possible to transfect multiple transcriptional units, the use of separate promoters and terminators for each gene leads to large plasmid sizes and possible interference between units. In many eukaryotic systems this challenge has been addressed through polycistronic expression mediated by 2A viral peptides, permitting efficient, co-regulated gene expression. Here, we screen the most commonly used 2A peptides, porcine teschovirus-1 2A (P2A),Thosea asignavirus 2A (T2A), equine rhinitis A virus 2A (E2A), and foot-and-mouth disease virus 2A (F2A), for activity inD. discoideumand find that all the screened 2A sequences are effective. However, combining the coding sequences of two proteins into a single transcript leads to notable strain-dependent decreases in expression level, suggesting additional factors regulate gene expression inD. discoideumthat merit further investigation. Our results show that P2A is the optimal sequence for polycistronic expression inD. discoideum, opening up new possibilities for genetic engineering in this model system.
Disruption of T-box transcription factor eomesa results in abnormal development of median fins in Oujiang color common carp Cyprinus carpio
Authors: Song Shiying , Du Bobo , Chung-Davidson Yu-Wen , Cui Wenyao , Li Yaru , Chen Honglin , Huang Rong , Li Weiming , Li Fei , Wang Chenghui , Ren Jianfeng
Published: March 2023

Median fins are thought to be ancestors of paired fins which in turn give rise to limbs in tetrapods. However, the developmental mechanisms of median fins remain largely unknown. Nonsense mutation of the T-box transcription factor eomesa in zebrafish results in a phenotype without dorsal fin. Compared to zebrafish, the common carp undergo an additional round of whole genome duplication, acquiring an extra copy of protein-coding genes. To verify the function of eomesa genes in common carp, we established a biallelic gene editing technology in this tetraploidy fish through simultaneous disruption of two homologous genes, eomesa1 and eomesa2. We targeted four sites located upstream or within the sequences encoding the T-box domain. Sanger sequencing data indicated the average knockout efficiency was around 40% at T1-T3 sites and 10% at T4 site in embryos at 24 hours post fertilization. The individual editing efficiency was high to about 80% at T1-T3 sites and low to 13.3% at T4 site in larvae at 7 days post fertilization. Among 145 mosaic F0 examined at four months old, three individuals (Mutant 1–3) showed varying degrees of maldevelopment in the dorsal fin and loss of anal fin. Genotyping showed the genomes of all three mutants were disrupted at T3 sites. The null mutation rates on the eomesa1 and eomesa2 loci were 0% and 60% in Mutant 1, 66.7% and 100% in Mutant 2, and 90% and 77.8% in Mutant 3, respectively. In conclusion, we demonstrated a role of eomesa in the formation and development of median fins in Oujiang color common carp and established an method that simultaneously disrupt two homologous genes with one gRNA, which would be useful in genome editing in other polyploidy fishes.
Feasibility of smartphone colorimetry of the face as an anaemia screening tool for infants and young children in Ghana
Authors: Wemyss Thomas Alan , Nixon-Hill Miranda , Outlaw Felix , Karsa Anita , Meek Judith , Enweronu-Laryea Christabel , Leung Terence S.
Published: March 2023

Background

Anaemia affects approximately a quarter of the global population. When anaemia occurs during childhood, it can increase susceptibility to infectious diseases and impair cognitive development. This research uses smartphone-based colorimetry to develop a non-invasive technique for screening for anaemia in a previously understudied population of infants and young children in Ghana.

Methods

We propose a colorimetric algorithm for screening for anaemia which uses a novel combination of three regions of interest: the lower eyelid (palpebral conjunctiva), the sclera, and the mucosal membrane adjacent to the lower lip. These regions are chosen to have minimal skin pigmentation occluding the blood chromaticity. As part of the algorithm development, different methods were compared for (1) accounting for varying ambient lighting, and (2) choosing a chromaticity metric for each region of interest. In comparison to some prior work, no specialist hardware (such as a colour reference card) is required for image acquisition.

Results

Sixty-two patients under 4 years of age were recruited as a convenience clinical sample in Korle Bu Teaching Hospital, Ghana. Forty-three of these had quality images for all regions of interest. Using a naïve Bayes classifier, this method was capable of screening for anaemia (<11.0g/dL haemoglobin concentration) vs healthy blood haemoglobin concentration (≥11.0g/dL) with a sensitivity of 92.9% (95% CI 66.1% to 99.8%), a specificity of 89.7% (72.7% to 97.8%) when acting on unseen data, using only an affordable smartphone and no additional hardware.

Conclusion

These results add to the body of evidence suggesting that smartphone colorimetry is likely to be a useful tool for making anaemia screening more widely available. However, there remains no consensus on the optimal method for image preprocessing or feature extraction, especially across diverse patient populations.
Outdoor environmental comfort evaluation for retail planning in a tropical business district using Integrated Environmental Modeller
Authors: Lai Po-Yen , Koh Wee Shing , Gopalan Harish , Liu Huizhe , Leong Dias , Lee Hyosoo , Goh Johnathan , Lim Jiun Yeu , Ang Jacob , Peh Gibert , Cher Gilbert , Eng Cheng Hui , Goh Jia Li , Tan Edmund , Tan James
Published: March 2023

This research proposes a simulation-based assessment of outdoor thermal and acoustic comfort for a planned business urban district in Singapore for retail planning using a customized OpenFOAM-centric multi-physics environmental simulation platform called the Integrated Environmental Modeller (IEM). IEM was employed to simulate the coupled impacts of solar radiation on wind and air temperature and wind and air temperature effects on traffic noise propagation in the district on the equinox and solstice day of the hottest period. Using IEM simulation results, we computed the thermal and acoustic comfort acceptability indicators derived from local field studies’ results. The spatial distribution of environmental comfort acceptability indicators in the worst-case scenario can be used to distinguish the zones exposed to thermal or noise influence. The noise-affected zones are near the main roads and overlap a part of the thermal-affected area. The thermal-affected area is almost everywhere in the studied sites in the worst-case scenario. Having outdoor retail spaces with both poor thermal and acoustic comfort is not recommended if the thermal and acoustic comfort cannot be improved simultaneously. For the high-level retail planning, a simplified parametric analysis considering solar irradiance blockage and wind speed enhancements, is provided. Considering the worst-case scenario, ≥50% thermal acceptability can be achieved by blocking 54%-68% solar irradiance among the pedestrian thoroughfares and the retail spaces. Coupled together, blocking the solar irradiance and enhancing the wind speed can further improve thermal comfort locally. These results can guide the retail mix (e.g., al fresco restaurants, pop-up kiosks etc.) near high footfall areas and provide reference for future plans combining landscape and infrastructure, (e.g., trees with shelter walkaways, green walls with outdoor ventilation fans etc.) taking into account the environmental acceptability of people working in or visiting the tropical urban district.
Applied machine learning to identify differential risk groups underlying externalizing and internalizing problem behaviors trajectories: A case study using a cohort of Asian American children
Authors: Adhikari Samrachana , You Shiying , Chen Alan , Cheng Sabrina , Huang Keng-Yen
Published: March 2023

Background

Internalizing and externalizing problems account for over 75% of the mental health burden in children and adolescents in the US, with higher burden among minority children. While complex interactions of multilevel factors are associated with these outcomes and may enable early identification of children in higher risk, prior research has been limited by data and application of traditional analysis methods. In this case example focused on Asian American children, we address the gap by applying data-driven statistical and machine learning methods to study clusters of mental health trajectories among children, investigate optimal predictions of children at high-risk cluster, and identify key early predictors.

Methods

Data from the US Early Childhood Longitudinal Study 2010–2011 were used. Multilevel information provided by children, families, teachers, schools, and care-providers were considered as predictors. Unsupervised machine learning algorithm was applied to identify groups of internalizing and externalizing problems trajectories. For prediction of high-risk group, ensemble algorithm, Superlearner, was implemented by combining several supervised machine learning algorithms. Performance of Superlearner and candidate algorithms, including logistic regression, was assessed using discrimination and calibration metrics via crossvalidation. Variable importance measures along with partial dependence plots were utilized to rank and visualize key predictors.

Findings

We found two clusters suggesting high- and low-risk groups for both externalizing and internalizing problems trajectories. While Superlearner had overall best discrimination performance, logistic regression had comparable performance for externalizing problems but worse for internalizing problems. Predictions from logistic regression were not well calibrated compared to those from Superlearner, however they were still better than few candidate algorithms. Important predictors identified were combination of test scores, child factors, teacher rated scores, and contextual factors, which showed non-linear associations with predicted probabilities.

Conclusions

We demonstrated the application of data-driven analytical approach to predict mental health outcomes among Asian American children. Findings from the cluster analysis can inform critical age for early intervention, while prediction analysis has potential to inform intervention programing prioritization decisions. However, to better understand external validity, replicability, and value of machine learning in broader mental health research, more studies applying similar analytical approach is needed.
Ten-year follow-up of auditory brainstem implants: From intra-operative electrical auditory brainstem responses to perceptual results
Authors: Veronese Sheila , Cambiaghi Marco , Tommasi Nicola , Sbarbati Andrea , Galvin John J.
Published: March 2023

The auditory brainstem implant (ABI) can provide hearing sensation to individuals where the auditory nerve is damaged. However, patient outcomes with the ABI are typically much poorer than those for cochlear implant recipients. A major limitation to ABI outcomes is the number of implanted electrodes that can produce auditory responses to electric stimulation. One of the greatest challenges in ABI surgery is the intraoperative positioning of the electrode paddle, which must fit snugly within the cochlear nucleus complex. While there presently is no optimal procedure for intraoperative electrode positioning, intraoperative assessments may provide useful information regarding viable electrodes that may be included in patients’ clinical speech processors. Currently, there is limited knowledge regarding the relationship between intraoperative data and post-operative outcomes. Furthermore, the relationship between initial ABI stimulation with and long-term perceptual outcomes is unknown. In this retrospective study, we reviewed intraoperative electrophysiological data from 24 ABI patients (16 adults and 8 children) obtained with two stimulation approaches that differed in terms of neural recruitment. The interoperative electrophysiological recordings were used to estimate the number of viable electrodes and were compared to the number of activated electrodes at initial clinical fitting. Regardless of the stimulation approach, the intraoperative estimate of viable electrodes greatly overestimated the number of active electrodes in the clinical map. The number of active electrodes was associated with long-term perceptual outcomes. Among patients with 10-year follow-up, at least 11/21 active electrodes were needed to support good word detection and closed-set recognition and 14/21 electrodes to support good open-set word and sentence recognition. Perceptual outcomes were better for children than for adults, despite a lower number of active electrodes.
Global characterization of gene expression in the brain of starved immature Rhodnius prolixus
Authors: Nevoa Jessica Coraiola , Latorre-Estivalis Jose Manuel , Pais Fabiano Sviatopolk-Mirsky , Marliére Newmar Pinto , Fernandes Gabriel da Rocha , Lorenzo Marcelo Gustavo , Guarneri Alessandra Aparecida
Published: March 2023

Background

Rhodnius prolixus is a vector of Chagas disease and has become a model organism to study physiology, behavior, and pathogen interaction. The publication of its genome allowed initiating a process of comparative characterization of the gene expression profiles of diverse organs exposed to varying conditions. Brain processes control the expression of behavior and, as such, mediate immediate adjustment to a changing environment, allowing organisms to maximize their chances to survive and reproduce. The expression of fundamental behavioral processes like feeding requires fine control in triatomines because they obtain their blood meals from potential predators. Therefore, the characterization of gene expression profiles of key components modulating behavior in brain processes, like those of neuropeptide precursors and their receptors, seems fundamental. Here we study global gene expression profiles in the brain of starved R. prolixus fifth instar nymphs by means of RNA sequencing (RNA-Seq).

Results

The expression of neuromodulatory genes such as those of precursors of neuropeptides, neurohormones, and their receptors; as well as the enzymes involved in the biosynthesis and processing of neuropeptides and biogenic amines were fully characterized. Other important gene targets such as neurotransmitter receptors, nuclear receptors, clock genes, sensory receptors, and takeouts genes were identified and their gene expression analyzed.

Conclusion

We propose that the set of neuromodulatory-related genes highly expressed in the brain of starved R. prolixus nymphs deserves functional characterization to allow the subsequent development of tools targeting them for bug control. As the brain is a complex structure that presents functionally specialized areas, future studies should focus on characterizing gene expression profiles in target areas, e.g. mushroom bodies, to complement our current knowledge.
Oncological and functional outcomes of high-risk and very high-risk prostate cancer patients after robot-assisted radical prostatectomy
Authors: Chen Wei-Hsin , Lee Yu Khun , Kuo Hann-Chorng , Wang Jen-Hung , Jiang Yuan-Hong
Published: March 2023

Purpose

This study investigated the oncological and functional outcomes of robot-assisted radical prostatectomy (RaRP) in high-risk and very high-risk prostate cancer patients.

Materials and methods

One hundred localized prostate cancer patients receiving RaRP from August 2015 to December 2020 were retrospectively enrolled. According to NCCN risk classification, patients were classified into two groups, below high-risk group, and high-risk/very high-risk group, to analyze continence outcome within postoperative year one and biochemical recurrence-free survival.

Results

The mean age of the cohort was 69.7 ± 7.4 years with a median follow-up of 26.4 (range 3.3–71.3) months. Among them, 53%, and 47% patients were below high-risk group, and high-risk/very high-risk group, respectively. The median biochemical recurrence-free survival of the entire cohort was 53.1 months. The high-risk/very high-risk group without adjuvant treatment had significantly worse biochemical recurrence-free survival than the high-risk/very high-risk group with adjuvant treatment (19.6 vs. 60.5 months, p = 0.029). Rates of postoperative stress urinary incontinence at 1 week, 1 month, and 12 months were 50.7%, 43.7%, and 8.5%, respectively. High-risk/very high-risk patients had significantly higher rates of stress urinary incontinence at postoperative week 1 (75.8% vs. 28.9%) and month 1 (63.6% vs. 26.3%) than the below high-risk group (both p < 0.01). Rates of stress urinary incontinence after RaRP did not differ between two groups from postoperative 3 months to 12 months. The factor of high-risk / very high-risk group was a predictor of immediate but not for long-term postoperative stress urinary incontinence.

Conclusions

High-risk and very high-risk prostate cancer patients receiving a combination of RaRP and adjuvant treatment had comparable biochemical recurrence-free survival to below high-risk prostate cancer patients. The high-risk/very high-risk factor impeded early but not long-term postoperative recovery of continence. RaRP can be considered a safe and feasible option for high-risk and very high-risk prostate cancer patients.
Sex differences in mild vascular cognitive impairment: A multimodal transcranial magnetic stimulation study
Authors: Cantone Mariagiovanna , Fisicaro Francesco , Ferri Raffaele , Bella Rita , Pennisi Giovanni , Lanza Giuseppe , Pennisi Manuela
Published: March 2023

Background

Sex differences in vascular cognitive impairment (VCI) at risk for future dementia are still debatable. Transcranial magnetic stimulation (TMS) is used to evaluate cortical excitability and the underlying transmission pathways, although a direct comparison between males and females with mild VCI is lacking.

Methods

Sixty patients (33 females) underwent clinical, psychopathological, functional, and TMS assessment. Measures of interest consisted of: resting motor threshold, latency of motor evoked potentials (MEPs), contralateral silent period, amplitude ratio, central motor conduction time (CMCT), including the F wave technique (CMCT-F), short-interval intracortical inhibition (SICI), intracortical facilitation, and short-latency afferent inhibition, at different interstimulus intervals (ISIs).

Results

Males and females were comparable for age, education, vascular burden, and neuropsychiatric symptoms. Males scored worse at global cognitive tests, executive functioning, and independence scales. MEP latency was significantly longer in males, from both sides, as well CMCT and CMCT-F from the left hemisphere; a lower SICI at ISI of 3 ms from the right hemisphere was also found. After correction for demographic and anthropometric features, the effect of sex remained statistically significant for MEP latency, bilaterally, and for CMCT-F and SICI. The presence of diabetes, MEP latency bilaterally, and both CMCT and CMCT-F from the right hemisphere inversely correlated with executive functioning, whereas TMS did not correlate with vascular burden.

Conclusions

We confirm the worse cognitive profile and functional status of males with mild VCI compared to females and first highlight sex-specific changes in intracortical and cortico-spinal excitability to multimodal TMS in this population. This points to some TMS measures as potential markers of cognitive impairment, as well as targets for new drugs and neuromodulation therapies.
Plasmodium schizogony, a chronology of the parasite’s cell cycle in the blood stage
Authors: Voß Yannik , Klaus Severina , Guizetti Julien , Ganter Markus
Published: March 2023

Malaria remains a significant threat to global health, and despite concerted efforts to curb the disease, malaria-related morbidity and mortality increased in recent years. Malaria is caused by unicellular eukaryotes of the genusPlasmodium, and all clinical manifestations occur during asexual proliferation of the parasite inside host erythrocytes. In the blood stage,Plasmodiumproliferates through an unusual cell cycle mode called schizogony. Contrary to most studied eukaryotes, which divide by binary fission, the parasite undergoes several rounds of DNA replication and nuclear division that are not directly followed by cytokinesis, resulting in multinucleated cells. Moreover, despite sharing a common cytoplasm, these nuclei multiply asynchronously. Schizogony challenges our current models of cell cycle regulation and, at the same time, offers targets for therapeutic interventions. Over the recent years, the adaptation of advanced molecular and cell biological techniques have given us deeper insight how DNA replication, nuclear division, and cytokinesis are coordinated. Here, we review our current understanding of the chronological events that characterize the unusual cell division cycle ofP.falciparumin the clinically relevant blood stage of infection.
An Atypical Presentation of Hemosuccus Pancreaticus Manifesting as Hematochezia
Authors: Sagalov Andrew , Siddiqui Harris , Nida Syeda , Rathinamanickam Harini , Al Turk Yahia , Sharma Pranav , Swied Abdul
Published: March 2023

Hemosuccus pancreaticus is a rare cause of upper gastrointestinal bleeding that is often associated with chronic pancreatitis. The bleeding usually manifests as melena because the source originates superior to the ligament of Treitz. We present a patient who was admitted for acute-on-chronic pancreatitis and ultimately developed hematochezia. Endoscopy revealed active oozing at the minor duodenal papilla. Computed tomography angiography identified active contrast extravasation at the gastroduodenal artery, and it was managed successfully with angioembolization. Our case emphasizes clinicians to consider hemosuccus pancreaticus as an alternative differential in a patient with a history of chronic pancreatitis manifesting with hematochezia.
Human Mpox Virus Proctitis With Persistent Rectal Ulcers on Sigmoidoscopy
Authors: Choy Alexa M. , Lyudmer Michael , Su Steven , Remotti Helen E. , Zucker Jason E. , Jodorkovsky Daniela
Published: March 2023

The 2022 Mpox outbreak has caused public health concerns worldwide. Mpox infection often manifests as papular skin lesions; other systemic complications have also been reported. We present the case of a 35-year-old man with HIV who presented with rectal pain and hematochezia and was found to have severe ulceration and exudate on sigmoidoscopy consistent with Mpox proctitis.
Novel Sequence of Endoscopic Therapy for the Management of Colonic Adenocarcinoma and Surrounding Adenoma
Authors: Scott Adam W. , Amin Khalid , Howard Justin R. , Amateau Stuart K.
Published: March 2023

An 80-year-old man with a history of an orthotopic heart transplant was found to have a 25 × 40 mm centrally ulcerated mass at the hepatic flexure during evaluation of anemia. Owing to comorbidities, the patient was deemed to be a poor surgical candidate and was referred to the advanced endoscopy team to explore palliative and potentially curative options. We present a novel sequence of intervention involving full-thickness resection with subsequent morcellation clean-up to achieve complete endoscopic removal of a neoplastic lesion.
Sexual Dimorphism in Brain Sirtuin-1 and m6A Methylated Sirtuin-1 mRNA, and in Protection with Post-Injury Anti-miR-200c treatment, after Experimental Stroke in Aged Mice
Authors:   Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, School of Medicine, Stanford, CA 94305, USA, Xu Lijun
Published: March 2023

We previously demonstrated that inhibition of miR-200c was protective against stroke in young adult male mice by augmenting sirtuin-1 (Sirt1). In the present study we assessed the role of miR-200c on injury, Sirt1, and bioenergetic and neuroinflammatory markers in aged male and female mice after experimental stroke. Mice were subjected to 1hr of transient middle cerebral artery occlusion (MCAO) and assessed for post-injury expression of miR-200c, Sirt1 protein and mRNA, N6-methyladenosine (m6A) methylated Sirt1 mRNA, ATP, cytochrome C oxidase activity, tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), infarct volume and motor function. MCAO induced a decrease in Sirt1 expression at 1d post-injury only in males. No differences in SIRT1 mRNA were observed between the sexes. Females had greater baseline miR-200c expression and a greater increase in miR-200c in response to stroke, while pre-MCAO levels of m6A SIRT1 was greater in females. Males had lower post-MCAO ATP levels and cytochrome C oxidase activity, and higher TNFα and IL-6. Post-injury intravenous treatment with anti-miR-200c reduced miR-200c expression in both sexes. In males, anti-miR-200c increased Sirt1 protein expression, reduced infarct volume, and improved neurological score. Conversely in females anti-miR-200c had no effect on Sirt1 levels and provided no protection against injury from MCAO. These results provide the first evidence of sexual dimorphism in the role of a microRNA in aged mice after experimental stroke and suggest sex-differences in epigenetic modulation of the transcriptome and downstream effects on miR biological activity may play a role in sexually dimorphic outcomes after stroke in aged brains.
Assessment of the Achievement Level Kandri Tourism Village, Gunungpati District, Semarang City
Authors: Kurniawan Abhi , Kurniati Rina
Published: March 2023

Kandri Tourism Village was founded in 2012, so it has been a tourism village for 9 years. In their development, in 2016 Kandri Tourism Village was classified as a "Pioneering Tourism Village" and in 2019 increased to a "Developing Tourism Village" based on data from the Central Java Province Tourism Village Assessment. These facts became the right momentum for researching the assessment of the Kandri Tourism Village program. The purpose of this study is to assess the achievement level of the Kandri Tourism Village which has been carried out until now. The research method uses a quantitative approach, while the sampling method uses simple random sampling and purposive sampling with a 100% response rate of the questionnaire, and is analyzed using scoring analysis techniques. The analysis process begins with the respondent giving a score to the tourism village variable, then recapitulating and calculating to get the average score for each variable, then summing it up to find out the final result of achievement level. The results showed that the achievement level of the Kandri Tourism Village program was 154 and was included in the "Developed Tourism Village" category. The benefit of this research is that it can provide information related to the achievement level of the Kandri Tourism Village program which is currently included in the "Developed Tourism Village" category and recommendations for improvement and development starting from the Aspects of Tourist Attractions, Accessibility, Infrastructure, Institutions, and Society in Kandri Tourism Village, so that the information and recommendations can be input for improving Kandri Tourism Village to be even better in the future.
The impact of maternal obesity on in vivo uterine contractile activity during parturition in the rat
Authors: Muir Ronan , Khan Raheela , Shmygol Anatoly , Quenby Siobhan , Elmes Matthew
Published: March 2023

Maternal obesity is associated with increased risk of prolonged and dysfunctional labor and emergency caesarean section. To elucidate the mechanisms behind the associated uterine dystocia, a translational animal model is required. Our previous work identified that exposure to a high‐fat, high‐cholesterol (HFHC) diet to induce obesity down‐regulates uterine contractile associated protein expression and causes asynchronous contractions ex vivo. This study aims to investigate the impact of maternal obesity on uterine contractile function in vivo using intrauterine telemetry surgery. Virgin female Wistar rats were fed either a control (CON, n = 6) or HFHC (n = 6) diet for 6 weeks prior to conception, and throughout pregnancy. On Day 9 of gestation, a pressure‐sensitive catheter was surgically implanted aseptically within the gravid uterus. Following 5 days recovery, intrauterine pressure (IUP) was recorded continuously until delivery of the 5th pup (Day 22). HFHC induced obesity led to a significant 1.5‐fold increase in IUP (p = 0.026) and fivefold increase in frequency of contractions (p = 0.013) relative to CON. Determination of the time of labor onset identified that HFHC rats IUP (p = 0.046) increased significantly 8 h prior to 5th pup delivery, which contrasts to CON with no significant increase. Myometrial contractile frequency in HFHC rats significantly increased 12 h prior to delivery of the 5th pup (p = 0.023) compared to only 3 h in CON, providing evidence that labor in HFHC rats was prolonged by 9 h. In conclusion, we have established a translational rat model that will allow us to unravel the mechanism behind uterine dystocia associated with maternal obesity.
Mechanistic insights into spontaneous transition from cellular alternans to ventricular fibrillation
Authors: You Tingting , Xie Yulong , Luo Cunjin , Zhang Kevin , Zhang Henggui
Published: March 2023

T‐wave alternans (TWA) has been used for predicting the risk of malignant cardiac arrhythmias and sudden cardiac death (SCD) in multiple clinical settings; however, possible mechanism(s) underlying the spontaneous transition from cellular alternans reflected by TWA to arrhythmias in impaired repolarization remains unclear. The healthy guinea pig ventricular myocytes under E‐4031 blocking IKr (0.1 μM, N = 12; 0.3 μM, N = 10; 1 μM, N = 10) were evaluated using whole‐cell patch‐clamp. The electrophysiological properties of isolated perfused guinea pig hearts under E‐4031 (0.1 μM, N = 5; 0.3 μM, N = 5; 1 μM, N = 5) were evaluated using dual‐ optical mapping. The amplitude/threshold/restitution curves of action potential duration (APD) alternans and potential mechanism(s) underlying the spontaneous transition of cellular alternans to ventricular fibrillation (VF) were examined. There were longer APD80 and increased amplitude and threshold of APD alternans in E‐4031 group compared with baseline group, which was reflected by more pronounced arrhythmogenesis at the tissue level, and were associated with steep restitution curves of the APD and the conduction velocity (CV). Conduction of AP alternans augmented tissue's functional spatiotemporal heterogeneity of regional AP/Ca alternans, as well as the AP/Ca dispersion, leading to localized uni‐directional conduction block that spontaneous facilitated the formation of reentrant excitation waves without the need for additional premature stimulus. Our results provide a possible mechanism for the spontaneous transition from cardiac electrical alternans in cellular action potentials and intercellular conduction without the involvement of premature excitations, and explain the increased susceptibility to ventricular arrhythmias in impaired repolarization. In this study, we implemented voltage‐clamp and dual‐optical mapping approaches to investigate the underlying mechanism(s) for the arrhythmogenesis of cardiac alternans in the guinea pig heart at cellular and tissue levels. Our results demonstrated a spontaneous development of reentry from cellular alternans, arising from a combined actions of restitution properties of action potential duration, conduction velocity of excitation wave and interplay between alternants of action potential and the intracellular Ca handling. We believe this study provides new insights into underlying the mechanism, by which cellular cardiac alternans spontaneously evolves into cardiac arrhythmias.
mNGS facilitates the accurate diagnosis and antibiotic treatment of suspicious critical CNS infection in real practice: A retrospective study
Authors: Feng Li , Chen Jiaxin , Luo Qiuyan , Su Miao , Chen Peisong , Lai Rong , Shen Cunzhou , Zhou Hongyan , Wang Haiyan , Sun Xunsha , Chen Ling , Xia Han , Feng Huiyu
Published: March 2023

Whether metagenomic next-generation sequencing (mNGS) could benefit patients with suspected severe central nervous system (CNS) infection in terms of diagnosis and antibiotic treatment remains unknown. We retrospectively analyzed 79 patients with suspected CNS infection and undertook mNGS. The value of mNGS was investigated in terms of identification of pathogen and guidance for the adjustment of antibiotic treatment. The relationship between the time of initiating mNGS since onset and the Glasgow Outcome Scale (GOS) score after 90-day follow-up were analyzed. Fifty out of 79 cases with suspicious severe CNS infection were finally diagnosed. Despite previous routine laboratory tests, mNGS further promoted the accurate identification of pathogens in 23 cases (47.9%). The sensitivity, specificity, and accuracy of mNGS test in this study were 84.0, 79.3, and 82.3%, respectively. Furthermore, mNGS facilitated the adjustment of empirical antibiotic treatments in 38 cases (48.1%). The time of taking mNGS since onset had an insignificant weak positive correlation with GOS after 90-day follow-up (r = −0.73, P = 0.08). mNGS facilitated the accurate identification of pathogens in suspicious severe CNS infections and promoted the accurate antibiotic therapy even empirical antibiotics were administrated. It should be taken as early as possible to improve the clinical outcome of patients with suspicious severe CNS infection.
Studies on the intercalation of calcium–aluminium layered double hydroxide-MCPA and its controlled release mechanism as a potential green herbicide
Authors: Bohari Farah Liyana , Sheikh Mohd Ghazali Sheikh Ahmad Izaddin , Dzulkifli Nur Nadia , Baharin Siti Nor Atika , Fatimah Is , Poddar Sandeep
Published: March 2023

The intercalation of 2-methyl-4-chlorophenoxyacetic acid (MCPA) herbicide into the interlayer matrix of calcium–aluminium layered double hydroxide (CaAl LDH) host has been successfully done via the co-precipitation method to form CaAl-MCPA nanocomposite, proposing an eco-friendly alternative with an adjusted delivery system for herbicide application. The intercalation process is supported by powder X-ray diffraction analysis with an expanded interlayer spacing from 8.6 to 19.6 Å for nanocomposite pH 13, which is due to the inclusion of larger size anion in the interlayer. Next, the absence of a nitrate peak at 1,326 cm−1 and the presence of a newly formed peak at 1,416 cm−1 in the Fourier transformed infrared spectroscopy analysis also confirmed the process of the intercalation. The significant decrease in nitrogen content to 0.50% indicates the intercalation of MCPA using the carbon, hydrogen, nitrogen, sulphur analyser. The release rate of the MCPA anion in the aqueous solutions is initially rapid, followed by the slow release in the order of phosphate > carbonate > chloride and followed the pseudo-second-order kinetic model. Hence, the conducted studies exhibit the successful intercalation of the MCPA herbicide anion and its controlled release mechanism as a potential hybrid green herbicide.
Eisenstein cohomology classes for GL
N
over imaginary quadratic fields
Authors: Bergeron Nicolas , Charollois Pierre , García Luis E.
Published: March 2023

We study the arithmetic of degree

N
-
1

{N-1}

Eisenstein cohomology classes for the locally symmetric spaces attached to

GL
N

{\mathrm{GL}_{N}}

over an imaginary quadratic field k. Under natural conditions we evaluate these classes on

(

N
-
1

)

{(N-1)}

-cycles associated to degree N extensions

L
/
k

{L/k}

as linear combinations of generalized Dedekind sums. As a consequence we prove a remarkable conjecture of Sczech and Colmez expressing critical values of L-functions attached to Hecke characters of L as polynomials in Kronecker–Eisenstein series evaluated at torsion points on elliptic curves with complex multiplication by k. We recover in particular the algebraicity of these critical values.
Erfolgsdeterminanten agnotologischer Strategien im Wissensmanagement
Authors: Reiss Michael
Published: March 2023

Agnotologische Strategien bezwecken mittels Desinformation, Hacking, Cyberangriffen, Propaganda, Betrug, Gaslighting, Nudging, Überflutung, Zensur, selektiver Geheimhaltung oder Zugriffsbarrieren zu den Wissensinfrastrukturen den Abbau von Wissen und das Disabling von Entscheidungen der jeweiligen Targets. Manipulatoren wollen bei den Targets eine irreführende, intransparente und/oder lückenhafte Wissensbasis schaffen. Der Manipulationserfolg hängt entscheidend vom Strategieverbund und von der Resilienz der Targets ab.
Dying in the Odor of Sanctity: Philip Neri and the Performance of Saintly Death in Catholic Reformation Rome
Authors: Santa Maria Thomas J.
Published: March 2023

For the four-hundredth anniversary of the canonization of Philip Neri, this paper proposes to analyze important elements of Neri’s sanctity. In particular, it focuses on what Oratorian hagiographers emphasized about his life and his holiness in their creation of his saintly reputation. I argue that death and dying was a central aspect of Philipine sanctity. In his life and ministries, modeling himself after Christian solitary ascetic monks and charitable caregiving mendicants, Philip Neri’s life revolved around death.
On the Canonization of the Founders of Religious Orders in Early Modern Times
Authors: Samerski Stefan
Published: March 2023

Neither before nor after the multiple canonization processes of 1622 have so many founders of religious orders been canonized at the same time. When examining in detail the historic processes of the founders, however, it is not generally possible to identify smooth and rapid procedures leading to their canonization. In the history of the Congregation of Rites, there were multiple hurdles and forms of resistance in the Congregation itself. The reason for the swift canonizations of 1622 was not in reality the founding of an order, but the ecclesiastical interests of the Pope and the Curia in highlighting the important protagonists of Catholic Reform. In addition, the new saints were associated with the struggle against heresies and the defence of the Apostolic See.