bluuebunny/crossref_metadata_2025 huggingface dataset:
Volume prediction for large brain metastases after hypofractionated gamma knife radiosurgery through artificial neural network
Authors: Moon Hyeong Cheol , Park Young Seok
Published: October 2022

The effectiveness of single-session gamma knife radiosurgery (GKRS) for small metastatic brain tumors has been proven, but hypofractionated GKRS (hfGKRS) for large brain metastases (BM) from the linear quadratic (LQ) model is uncertain. The purpose of this study was to investigate volume changes large BM after hfGKRS from the LQ model and predict volume changes using artificial neural network (ANN). We retrospectively investigated the clinical findings of 28 patients who underwent hfGKRS with large BM (diameter >3 cm or volume >10 cc). A total of 44 tumors were extracted from 28 patients with features. We randomly divided 30 large brain tumors as training set and 14 large brain tumors as test set. To predict the volume changes after hfGKRS, we used ANN models (single-layer perceptron (SLP) and multi-layer perceptron (MLP)). The volume reduction was 96% after hfGKRS for large BM from the LQ model. ANN model predicted volume changes with 70% and 80% accuracy for SLP and MLP, respectively. Even in large BM, hfGKRS from the LQ model could be a good treatment option. Additionally, the MLP model could predict volume changes with 80% accuracy after hfGKRS for large BM.
Curcumin protects PC12 cells from a high glucose-induced inflammatory response by regulating the miR-218-5p/TLR4 axis
Authors: Cui Yuan , Song Hong-Tao , Zhang Pei , Yin Xiao , Wang Ying , Wei Xuan , Jia Xin-Ju
Published: October 2022

Background:

Curcumin exerts a protective effect on diabetic encephalopathy (DN), It is known for its potent neuroprotective, anti-inflammatory, antioxidant, and anticancer properties. However, the underlying mechanisms of curcumin’s neuroprotective effects resulting from high glucose (HG)-induced injuries remain unknown. The purpose of this study is to identify the protective mechanism of Curcumin in the DN.

Methods:

In this study, pheochromocytoma cells (PC12 cells) were pretreated with different concentrations of Curcumin and then co-treated with Curcumin and glucose for 48 hours, and the cell viability was evaluated by CCK-8, the expression of the inflammatory mediators were detected by ELISA, the miR-218-5p and toll-like receptors (TLR4) level were examined by both quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, the potential target genes of miR-218-5p were identified using luciferase reporter assay.

Results:

The viability of PC12 cells treated with HG was significantly reduced in a dose- and time-dependent manner. Cotreatment of curcumin with HG significantly increased cell viability. Curcumin inhibited the expression of the inflammatory mediators, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), and induced the expression of the anti-inflammatory mediator interleukin-10 (IL-10). Curcumin upregulated the levels of miR-218-5p and downregulated the expression of TLR4 in HG-treated PC12 cells. The curcumin-induced anti-inflammatory effect was abrogated by a miR-218-5p inhibitor and overexpression of TLR4. The results suggest that curcumin ameliorates the inflammatory response by upregulating miR-218-5p levels in PC12 cells.

Conclusions:

Our results indicate a protective role for curcumin in PC12 cells and suggest that it should be considered for the prophylactic treatment of DN in the future.
Differential expression of miRNAs in bronchoalveolar lavage fluid and plasma from patients with chronic obstructive pulmonary disease
Authors: Hu Jianwu , Wang Weina , Lu Qiaofa , Du Lifen , Qin Tian
Published: October 2022

Micro RNAs (MiRNAs) act as a key regulator participating in various biological process, and the roles of that play in chronic obstructive pulmonary disease (COPD) are discovered. However, recent pharmacological treatment for COPD focus on alleviating symptoms and reducing the risk events. The heterogeneous COPD causes variable responses to pharmacological interventions. COPD treatment has gradually developed into precision medicine, integrating clinical and biomarker information to optimize personalized therapy. Thus, targeting miRNAs represents a promising strategy for COPD individual therapy. Twelve COPD patients, 7 community-acquired pneumonia and 4 normal people were recruited. Total RNAs were collected from the bronch alveolar lavage cells and peripheral blood plasma of each participant. miRNAs were profiled by microarray and systematically compared between patients with different groups. Bioinformatic analysis identified pathways relevant to the pathogenesis of COPD. Next, the target pathway networks were mapped. Compared different groups, we obtain differential expression of miRNAs (Q value (Adjusted P value) < .05 and |log2FC| >2). Gene ontology enrichment analyses showed that differentially expressed miRNAs function as regulators in different modules of cellular component, molecular function and biological process. Kyoto Encyclopedia of Genes and Genomes enrichment analyses suggested that signals, such as MAPK signaling pathway, Ras signaling pathway, FoxO signaling pathway and oxidative stress may participate in the pathogenesis of COPD. In the miRNAs target pathway networks, novel-hsa-miR26-3p or hsa-miR-3529-3p/CDC42/MAPK signaling pathway may play a role in regulating COPD. Our findings demonstrate critical roles of the miRNAs in COPD molecular pathology. The data support a plausible mechanism that miRNAs may be involved in the development of COPD by affecting the inflammatory and oxidative stress. Moreover, hsa-miR-4748/CDC42/MAPK signaling pathway may contribute to the pathogenesis of COPD, providing a potential novel therapeutic strategy in COPD.
The gene variant for desmin rs1058261 may protect against combined cancer and cardiovascular death, the Tampere adult population cardiovascular risk study
Authors: Piesanen Jaakko , Kunnas Tarja , Nikkari Seppo T
Published: October 2022

Desmin-containing intermediate filaments are a part of muscle cytoskeleton. We have previously reported that the wild-type cytosine/cytosine genotype of a common Desmin synonymous single nucleotide polymorphism (C > T) (rs1058261) associated with cardiovascular diseases in a cohort of subjects from the Tampere adult population cardiovascular risk study. We now examined whether rs1058261 also associates with early death by following the cohort of 801 subjects from the age of 50 up to the age of 65. Outcomes for death were collected from the National Statistics Centre. Linkage disequilibrium analysis and gene expression correlations for rs1058261 were done in silico. With follow-up, subjects with wild-type cytosine/cytosine genotype had higher incidence of cancer deaths (odds ratio [OR] 5.27, confidence interval [CI] 1.160–23.946, P = .031), combined deaths from cardiovascular diseases or cancers (OR 3.92, CI 1.453–10.596, P = .007), and “hard” acute cardiovascular disease events (early myocardial infarction and/or death) (OR 3.90, CI 1.287–11.855, P = .016) compared to subjects with the T-allele. The in silico results of linkage disequilibrium and gene expression analyses showed negative gene expression sizes associated with rs1058261, which theoretically decreases desmin expression. Our findings suggest that variation rs1058261 in Desmin may serve as a surrogate marker for other variations involved in decrease of deaths from combined cancer and cardiovascular disease.
Body composition and pelvic fat distribution are associated with prostate cancer aggressiveness and can predict biochemical recurrence
Authors: Chien Yu-Hsuan , Hsieh Ming-Li , Sheng Ting-Wen , Chang Ying-Hsu , Wang Li-Jen , Chuang Cheng-Keng , Pang See-Tong , Wu Chun-Te , Shao I-Hung
Published: October 2022

This study evaluated the effect of body composition and pelvic fat distribution on the aggressiveness and prognosis of localized prostate cancer. This study included patients who underwent robot-assisted radical prostatectomy with positive surgical margins. Clinicodemographic data were collected from patients’ medical reports. Pretreatment magnetic resonance images (MRI) obtained for cancer staging were reviewed by a single radiologist to calculate pelvic fat distribution and body composition. We correlated these body composition parameters with initial prostate-specific antigen (iPSA), Gleason score, extracapsular tumor extension, and biochemical recurrence (BCR)–free survival. The iPSA was significantly associated with body mass index (BMI; P = .027), pelvic fat volume (P = .004), and perirectal fat volume (P = .001), whereas the Gleason score was significantly associated with BMI only (P = .011). Tumor extracapsular extension was significantly associated with increased periprostatic fat volume (P = .047). Patients with less subcutaneous fat thickness (<2.4 cm) had significantly poor BCR–free survival (P = .039). Pelvic fat distribution, including pelvic fat volume, perirectal fat volume, and periprostatic fat volume, were significantly correlated with prostate cancer aggressiveness. Patients with less subcutaneous fat had an increased risk of BCR after radical prostatectomy.
The ‘-ics’ of male reproduction: genomics, epigenetics, proteomics, metabolomics, and microbiomics
Authors: Kang Caroline , Bertolla Ricardo , Pagani Rodrigo
Published: October 2022

Purpose of review

To review the most current findings, from the past 2 years, in various ‘-ics’ fields in male infertility, with a specific focus on nonobstructive azoospermia, the most severe form, and varicocele, the most common correctable cause of male infertility.

Recent findings

Recent studies confirm previously identified causes and identify previously unknown genetic mutations as causes for nonobstructive azoospermia and varicocele.

Infertility is a common problem for couples with approximately half of cases attributable to male factor infertility. Although advances in assisted reproductive technology have permitted many more men with infertility to father biological children, the majority of infertile men continue to have unknown causes. The recent explosion of the ‘-ics’ fields, including genomics, epigenetics, proteomics, metabolomics, and microbiomics, has shed light on previously unknown causes for various diseases. New information in these fields will not only shed light on the pathogenesis of these conditions but also may shift the paradigm in clinical testing that may allow clinicians to provide more precise counseling and prognostic information for men with infertility.
Management of Malignant Bowel Obstruction
Authors: Jivraj Nazlin , Lee Yeh Chen , Tinker Lisa , Bowering Valerie , Ferguson Sarah E. , Croke Jennifer , Karakasis Katherine , Chawla Tanya , Lau Jenny , Ng Pamela , Dhar Preeti , Shlomovitz Eran , Buchanan Sarah , Dhani Neesha , Oza Amit M. , Stuart-McEwan Terri , Lheureux Stephanie
Published: October 2022

Background:

Malignant bowel obstruction (MBO) in patients with advanced gynecologic cancer (GyCa) can negatively impact clinical outcomes and quality of life. Oncology nurses can support these patients with adequate tools/processes.

Problem:

Patients with GyCa with/at risk of MBO endure frequent emergency or hospital admissions, impacting patient care.

Approach:

Optimizing oncology nurses' role to improve care for patients with GyCa with/at risk of MBO, the gynecology oncology interprofessional team collaborated to develop a proactive outpatient nurse-led MBO model of care (MOC).

Outcomes:

The MBO MOC involves a risk-based algorithm engaging interdisciplinary care, utilizing standardized tools, risk-based assessment, management, and education for patients and nurses. The MOC has improved patient-reported confidence level of bowel self-management and decreased hospitalization. Following education, nurses demonstrated increased knowledge in MBO management.

Conclusions:

An outpatient nurse-led MBO MOC can improve patient care and may be extended to other cancer centers, fostering collaboration and best practice.
Examining QI Knowledge Among Frontline Nurses and Nurse Leaders
Authors: Prochnow Laura , DiClemente Linda , Riley Penny , Tschannen Dana
Published: October 2022

Background:

Frontline nurses deliver direct patient care and by participating in quality improvement (QI) can have an impact on health care quality and safety. Unfortunately, nurses are not participating in QI, which may be due to a lack of QI knowledge.

Purpose:

The purpose of this study was to evaluate nurses QI knowledge utilizing the revised Quality Improvement Knowledge Application Tool (QIKAT-R), with newly created nursing scenarios, among frontline nurses and nurse leaders.

Methods:

Using a cross-sectional design, this study evaluated nurses QI knowledge utilizing the QIKAT-R.

Results:

Overall, QI knowledge among nurses was low. The frontline nurses (n = 44) scored higher than nurse leaders (n = 11) on overall QI knowledge scores, although not significant. Frontline nurses scored higher in QI knowledge related to aim and measure, whereas nurse leaders scored higher in change.

Conclusions:

Understanding frontline nurses QI knowledge, such as with the QIKAT-R with newly created nursing scenarios, can assist with creating targeted strategies for improving overall engagement in QI.
Relief of chronic pain associated with increase in midline frontal theta power
Authors: Rustamov Nabi , Wilson Elizabeth A. , Fogarty Alexandra E. , Crock Lara W. , Leuthardt Eric C. , Haroutounian Simon
Published: October 2022

Introduction:

There is a need to identify objective cortical electrophysiological correlates for pain relief that could potentially contribute to a better pain management. However, the field of developing brain biomarkers for pain relief is still largely underexplored.

Objectives:

The objective of this study was to investigate cortical electrophysiological correlates associated with relief from chronic pain. Those features of pain relief could serve as potential targets for novel therapeutic interventions to treat pain.

Methods:

In 12 patients with chronic pain in the upper or lower extremity undergoing a clinically indicated nerve block procedure, brain activity was recorded by means of electroencephalogram before and 30 minutes after the nerve block procedure. To determine the specific cortical electrophysiological correlates of relief from chronic pain, 12 healthy participants undergoing cold-pressor test to induce experimental acute pain were used as a control group. The data were analyzed to characterize power spectral density patterns of pain relief and identify their source generators at cortical level.

Results:

Chronic pain relief was associated with significant delta, theta, and alpha power increase at the frontal area. However, only midfrontal theta power increase showed significant positive correlation with magnitude of reduction in pain intensity. The sources of theta power rebound were located in the left dorsolateral prefrontal cortex (DLPFC) and midline frontal cortex. Furthermore, theta power increase in the midline frontal cortex was significantly higher with chronic vs acute pain relief.

Conclusion:

These findings may provide basis for targeting chronic pain relief via modulation of the midline frontal theta oscillations.
Pharmacokinetics, Tolerability, and Safety of Doravirine and Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate Fixed-Dose Combination Tablets in Adolescents Living With HIV: Week 24 Results From IMPAACT 2014
Authors: Melvin Ann J. , Yee Ka Lai , Gray Kathryn P. , Yedla Mounika , Wan Hong , Tobin Nicole H. , Teppler Hedy , Campbell Havilland , McCarthy Katie , Scheckter Rachel , Aurpibul Linda , Ounchanum Pradthana , Rungmaitree Supattra , Cassim Hassena , McFarland Elizabeth , Flynn Patricia , Cooper Ellen , Krotje Chelsea , Townley Ellen , Moye Jack , Best Brookie M. ,   for the IMPAACT 2014 study team
Published: October 2022

Background:

We studied the pharmacokinetics (PK) and safety of 100-mg doravirine and doravirine/lamivudine/tenofovir disoproxil fumarate fixed-dose combination (100/300/300 mg DOR FDC) treatment in adolescents with HIV-1.

Methods:

Adolescents ages 12 to younger than 18 years were enrolled in 2 sequential cohorts. Cohort 1 evaluated intensive PK and short-term safety of 100-mg single-dose doravirine in adolescents ≥35 kg. Cohort 2 participants either initiated treatment with DOR FDC (antiretroviral (ARV)-naïve) or switched to DOR FDC from a previous ARV regimen (virologically suppressed). The first 10 Cohort 2 participants had intensive PK evaluations, and safety, sparse PK, and HIV RNA were assessed through week 24.

Results:

Fifty-five adolescents, median age 15.0 years and baseline weight 51.5 kg, were enrolled. Nine participants completed Cohort 1 PK assessments (8 of the 9 participants weighed ≥45 kg) and 45 initiated study drug in Cohort 2. The doravirine geometric mean (GM) AUC0–∞ was 34.8 μM∙hour, and the GM C24 was 514 nM after a single dose, with a predicted steady-state GM C24,ss,pred of 690 nM. Cohort 2 enrolled adolescents weighing ≥45 kg. Plasma concentrations of doravirine, tenofovir, and lamivudine achieved by Cohort 2 participants were similar to those reported in adults. No drug-related serious or grade 3 or 4 adverse events occurred. Forty-two of 45 participants (93.3%; 95% CI: [81.7, 98.6]) achieved or maintained HIV-1 RNA <40 copies/mL.

Conclusions:

Doravirine and DOR FDC achieved target PK in adolescents with HIV-1. DOR FDC was well-tolerated and maintained excellent virologic efficacy through 24 weeks, offering a favorable option for adolescents.
Using Mirror Therapy to Optimize the Efficacy of Balance Programs for Older Adults With Poststroke Balance Impairment
Authors: Armat Mohammad Reza , Mortazavi Hamed , Akbari Hadi , Emami Zeydi Amir , Sarani Arezoo
Published: October 2022

Purpose

Poststroke rehabilitation is an inevitable element of the treatment for stroke survivors. This study aimed to investigate the effect of balance training with mirror therapy in older adults with poststroke balance impairment.

Design/Methods

The study adopted a two-arm randomized clinical trial and included 38 older adults with poststroke balance impairment. The intervention group received balance exercises with mirror therapy, whereas the control group received the same balance exercises without mirror therapy (a nonreflective plate was used instead). The patient outcome, the balance score, was measured using the Berg Balance Scale. Analysis of covariance was used for statistical analysis.

Results

Results showed that balance exercises combined with mirror therapy were significantly more effective than balance exercises without mirror therapy in improving balance in the stroke survivors (p < .001).

Conclusion

Mirror therapy combined with regular balance exercises is an effective and practical method for enhancing balance in older adults suffering from balance impairment.

Clinical Relevance

Balance training combined with mirror therapy may be included in the rehabilitation programs of older adults with poststroke balance impairment.
Anosognosia for Hemiplegia and Falls After Stroke
Authors: Byrd Elizabeth M. , Strang Christianne E. , Qiao Xiaofei , Loan Lori , Miltner Rebecca S. , Jablonski Rita A.
Published: October 2022

Purpose

The aim of this study was to explore the association between the presence and severity of anosognosia for hemiplegia (AHP) and falls in stroke survivors.

Design

A prospective, correlational research design was utilized.

Methods

Primary instrumentation included demographic information and the Visual-Analogue Test for Anosognosia for motor impairment (VATA-m). Correlational and regression analyses were performed between a priori variables.

Results

There was no statistically significant relationship found between AHP and falls. An incidental finding included that clinicians erroneously charted that their patients were aware of their physical limitations 100% of the time, which indicates that there is discord between clinicians and patients regarding physical limitations.

Conclusions

Though no statistically significant relationship was found between AHP and falls, the incidental finding of dissonance between the patient and the clinician has important clinical implications.

Relevance

The relationship between AHP and stroke rehabilitation outcomes is still not understood, and incorporating part of the VATA-m into patient assessment could improve clinician understanding of patient awareness.
Treatment of Anaphylaxis After Injection of Stem Cell Exosomes With 5-Fluorouracil and Triamcinolone Acetonide
Authors: Zhuang Jun , Chen Youbai , Hu Jintian
Published: October 2022

Using stem cell exosomes to treat alopecia is a new treatment in plastic surgery. However, there are few reports on the complications of this treatment. This study describes a method of using 5-fluorouracil combined with triamcinolone acetonide to treat allergic reactions caused by stem cell exosomes injection. The ultrasound results before treatment showed that the thickness of subcutaneous soft tissue in the forehead was 0.35 cm,the length and short diameter of left retroauricular lymph nodes were 1.11 and 0.46 cm, and the length and short diameter of right retroauricular lymph nodes were 1.10 and 0.45 cm. After treatment, the thickness of subcutaneous soft tissue in the forehead was 0.20 cm, the length and short diameter of the lymph nodes behind the left ear were 1.06 and 0.40 cm, respectively, and the length and short diameter of the lymph nodes behind the right ear were 1.06 and 0.36 cm, respectively. The results of treatment proved that this treatment had a therapeutic effect on the allergy of patients.
No Brain Signature of Prediction Error to Unattended Visual Stimuli Despite Early Brain Encoding of the Stimuli
Authors: Male Alie G. , O’Shea Robert P.
Published: October 2022

Prediction error is a basic component of predictive-coding theory of brain processing. According to the theory, each stage of brain processing of sensory information generates a model of the current sensory input; subsequent input is compared against the model and only if there is a mismatch, a prediction error, is further processing performed. Recently, Smout et al. [1] found that a signature of prediction error, the visual (v) mismatch negativity (MMN), for a fundamental property of visual input—its orientation—was absent without attention on the stimuli. This is remarkable because the weight of evidence for MMNs from audition and vision is that they occur without attention. To resolve this discrepancy, we conducted an experiment addressing two alternative explanations for Smout et al.’s finding: that it was from a lack of reproducibility or that participants’ visual systems did not encode the stimuli when attention was on something else.

We conducted a similar experiment to Smout et al.’s. We showed 21 participants sequences of identically oriented Gabor patches, standards, and, unpredictably, otherwise identical, Gabor patches differing in orientation by ±15°, ±30°, and ±60°, deviants. To test whether participants encoded the orientation of the standards, we varied the numbers of standards preceding a deviant, allowing us to search for a decrease in activity with the number of repetitions of standards—repetition suppression. We diverted participants’ attention from the oriented stimuli with a central, letter-detection task.

We reproduced Smout et al.’s finding of no vMMN without attention, strengthening their finding. We also found that our participants showed repetition suppression: they did encode the stimuli pre-attentively. We also found early processing of deviants. We discuss whether this earlier processing of deviants may be why no further processing, in the vMMN time window, occurs.
Initiation of HIV-1 Gag lattice assembly is required for cytoplasmic recognition of the viral genome packaging signal
Authors: Lei Xiao , Gonçalves-Carneiro Daniel , Zang Trinity M. , Bieniasz Paul D.
Published: October 2022

The encapsidation of HIV-1 genomic RNA into virions is enabled by the binding of the nucleocapsid (NC) domain of the HIV-1 Gag polyprotein to the structured viral RNA packaging signal (Ψ) at the 5’ end of the viral genome. However, the subcellular location and oligomeric status of Gag during the initial Gag-Ψ encounter remains uncertain. Domains other than NC, such as capsid (CA), may therefore indirectly affect RNA recognition. To investigate the contribution of Gag domains to Ψ recognition in a cellular environment, we performed protein-protein crosslinking and protein-RNA crosslinking immunoprecipitation coupled with sequencing (CLIP-seq) experiments. We demonstrate that NC alone does not bind specifically to Ψ in living cells, whereas full-length Gag and a CANC subdomain bind to Ψ with high specificity. Perturbation of the Ψ RNA structure or NC zinc fingers affected CANC:Ψ binding specificity. Notably, CANC variants with substitutions that disrupt CA:CA dimer, trimer or hexamer interfaces in the immature Gag lattice also affected RNA binding, and mutants that were unable to assemble a nascent Gag lattice completely lost the ability to specific bind to Ψ. Artificially multimerized NC domains did not specifically bind Ψ. CA variants with substitutions in inositol phosphate coordinating residues that prevent CA hexamerization were also deficient in Ψ binding and second-site revertant mutants that restored CA assembly also restored specific binding to Ψ. Overall, these data indicate that the correct assembly of a nascent immature CA lattice is required for the specific interaction between Gag and Ψ in cells.
The Persistent Mortality and Heart Failure Burden of Anterior ST-Segment Elevation Myocardial Infarction Following Primary Percutaneous Coronary Intervention
Authors: Martin Jack L.
Published: October 2022

Background

There is limited data on temporal trends in clinical outcomes after ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) particularly beyond one year and in real world populations that include patients often excluded from randomized trials.

Objectives

We sought to compare the temporal trends in the incidence of death and re-hospitalization for congestive heart failure (CHF) following anterior STEMI in a Medicare cohort of beneficiaries treated with primary PCI in 2005 (n = 1,479) with those treated in 2016 through quarter (Q) 2 of 2017 (n = 22,432).

Methods

Outcomes were examined using both descriptive and regression analysis to control for differences in patient clinical characteristics over time.

Results

The 1-year mortality rate trended higher in the late cohort (10.3 vs 8.9%, p=0.068). The 2-year mortality rate was significantly higher in the late cohort (14.5 vs 11.4%, p<0.01). The one-year re-hospitalization for CHF was lower in the late cohort (10.6 versus 16.7%, p<0.01), but the 2-year rate was unchanged (19.3 vs 20.7%, p=0.55). After adjustment for covariates with two models there were highly statistically significant increases in mortality at 1-year (2.3 – 4.1%) and 2-years (4.2 – 6.5%) in the late cohort. The unadjusted trends in re-hospitalization for CHF persisted after adjustment for covariates.

Conclusions

Despite prior improvements in STEMI outcomes in the reperfusion era related to the broad adoption of timely PCI, there is a persistent high mortality and CHF burden in patients with anterior STEMI. New strategies that address reperfusion injury and enhance myocardial salvage are needed.
Fast prediction in marmoset reach-to-grasp movements for dynamic prey
Authors: Shaw Luke , Wang Kuan Hong , Mitchell Jude
Published: October 2022

Primates have evolved sophisticated visually guided reaching behaviors for interacting with dynamic objects, such as insects during foraging(P. S. Archambault, Ferrari-Toniolo, & Battaglia-Mayer, 2011; Bicca-Marques, 1999; Ngo et al., 2022; Smith & Smith, 2013; Sustaita et al., 2013). Reaching control in dynamic natural conditions requires active prediction of the target’s future position to compensate for visuo-motor processing delays and enhance online movement adjustments(Catania, 2009; Desmurget & Grafton, 2000; Fujioka, Aihara, Sumiya, Aihara, & Hiryu, 2016; Merchant & Georgopoulos, 2006; Mischiati et al., 2015; R. Shadmehr, Smith, & Krakauer, 2010; Wolpert & Kawato, 1998). Past reaching research in non-human primates mainly focused on seated subjects engaged in repeated ballistic arm movements to either stationary targets, or targets that instantaneously change position during the movement(Philippe S. Archambault, Caminiti, & Battaglia-Mayer, 2009; Battaglia-Mayer et al., 2013; Dickey, Amit, & Hatsopoulos, 2013; Georgopoulos, Kalaska, Caminiti, & Massey, 1983; Georgopoulos, Kalaska, & Massey, 1981). However, those approaches impose task constraints that limit the natural dynamics of reaching. A recent field study in marmoset monkeys highlights predictive aspects of visually-guided reaching during insect prey capture among wild marmoset monkeys(Ngo et al., 2022). To examine the complementary dynamics of similar natural behavior within a laboratory context we developed an ecologically motivated unrestrained reach-to-grasp task involving live crickets. We used multiple high-speed video cameras to capture the movements of marmosets and crickets stereoscopically and applied machine vision algorithms for marker-free object and hand tracking. Contrary to estimates under traditional constrained reaching paradigms, we find that reaching for dynamic targets can operate at incredibly short visuo-motor delays around 80 milliseconds, rivaling the speeds that are typical of the oculomotor systems during closed-loop visual pursuit(Cloherty, Yates, Graf, DeAngelis, & Mitchell, 2020). Multivariate linear regression modeling of the kinematic relationships between the hand and cricket velocity revealed that predictions of the expected future location can compensate for visuo-motor delays during fast reaching. These results suggest a critical role of visual prediction facilitating online movement adjustments for dynamic prey.
Influence of ethnicity and consanguinity on the genetic architecture of Hypertrophic Cardiomyopathy: insights from an understudied population
Authors: Allouba Mona , Walsh Roddy , Afify Alaa , Hosny Mohammed , Halawa Sarah , Galal Aya , Fathy Mariam , Theotokis Pantazis I. , Boraey Ahmed , Ellithy Amany , Buchan Rachel , Govind Risha , Whiffin Nicola , Anwer Shehab , ElGuindy Ahmed , Ware James S. , Barton Paul J.R. , Aguib Yasmine , Yacoub Magdi
Published: October 2022

Hypertrophic cardiomyopathy (HCM) is an inherited cardiac condition characterized by phenotypic heterogeneity that could partly be explained by the variability in genetic variants contributing to disease. Accurate interpretation of these variants constitutes a major challenge for diagnosis and implementing precision medicine, especially in understudied populations. Here, we leverage ancestry-matched Egyptian patients (n=514) and deeply-phenotyped controls (n=400) to accurately define the genetic architecture of HCM. We also compare HCM variation between Egyptian and predominantly European patients to identify genetic features unique to consanguineous populations in Middle East and North Africa (MENA), which are likely to represent important contributors to disease. We report a higher prevalence of homozygous variants in Egyptian patients (4.1% vs 0.1%, p-value=2×10×7), with variants in the minor HCM genesMYL2, MYL3andCSRP3more likely to present in homozygosity than the major genes (MYH7, MYBPC3), suggesting that these variants are less penetrant in heterozygosity. Biallelic variants in the recessive HCM geneTRIM63were detected in 2.1% of patients (5-fold greater than European patients), highlighting the importance of recessive inheritance/genes in consanguineous populations. Finally, significantly fewer rare variants detected in Egyptian HCM patients could be classified as (likely) pathogenic compared to Europeans (40.8% vs. 61.6%, p-value=1.6×10×5) due to the underrepresentation of MENA populations in current HCM databases. This proportion increased to 53.8% after incorporating methods that compare variant frequencies between Egyptian patients and controls. Together, our findings demonstrate that studying consanguineous populations reveals novel insights with relevance to genetic testing and our understanding of the genetic architecture of HCM.
MS2Prop: A machine learning model that directly generatesde novopredictions of drug-likeness of natural products from unannotated MS/MS spectra
Authors: Voronov Gennady , Lightheart Rose , Frandsen Abe , Bargh Brian , Haynes Sarah E. , Spencer Elizabeth , Schoenhardt Katherine E. , Davidson Christina , Schaum Andre , Macherla Venkat R. , DeBloois Erik , Healey David , Kind Tobias , Dorrestein Pieter , Colluru Viswa , Butler Thomas , Yu Marvin S.
Published: October 2022

Mass spectrometry (MS) is a fundamental analytical tool for the study of complex molecular mixtures and in natural products drug discovery and metabolomics specifically, due to its high sensitivity, specificity, and throughput. A major challenge, however, is the lack of structurally annotated mass spectra for these applications. This deficiency is particularly acute for analyses conducted on extracts or fractions that are largely chemically undefined. This work describes the use of mass spectral data in a fundamentally different manner than structure determination; to predict properties or activities of structurally unknown compounds without the need for defined or deduced chemical structure using a machine learning (ML) model, MS2Prop. The model’s predictive accuracy and scalability is benchmarked against commonly used methods and its performance demonstrated in a natural products drug discovery setting. A new cheminformatic subdiscipline, quantitative spectra-activity relationships (QSpAR), using spectra rather than chemical structure as input, is proposed to describe this approach and to distinguish it from structure based quantitative methods.
GTF2I dosage regulates neuronal differentiation and social behavior in 7q11.23 neurodevelopmental disorders
Authors: Lopez-Tobon Alejandro , Shyti Reinald , Villa Carlo Emanuele , Cheroni Cristina , Fuentes-Bravo Patricio , Trattaro Sebastiano , Caporale Nicolò , Troglio Flavia , Tenderini Erika , Mihailovich Marija , Skaros Adrianos , Gibson William T. , Cuomo Alessandro , Bonaldi Tiziana , Mercurio Ciro , Varasi Mario , Osborne Lucy , Testa Giuseppe
Published: October 2022

Copy number variations at 7q11.23 cause neurodevelopmental disorders with shared and opposite manifestations. Deletion causes Williams-Beuren syndrome (WBS), while duplication causes 7q11.23 microduplication syndrome (7Dup). Converging evidence indicatesGTF2I, from the 7q11.23 locus, is a key mediator of the cognitive-behavioral phenotypes associated with WBS and 7Dup. Here we integrate molecular profiling of patient-derived cortical organoids (COs) and transgenic mouse models to dissect 7q11.23 disease mechanisms. Proteomic and transcriptomic profiling of COs revealed opposite dynamics of neural progenitor proliferation and transcriptional imbalances, leading to precocious excitatory neuron production in 7Dup. The accelerated excitatory neuron production in 7Dup COs could be rescued byGTF2Iknockdown. Transgenic mice withGtf2iduplication recapitulated early neuronal differentiation defects and ASD-like behaviors. Remarkably, inhibition of LSD1, a downstream effector ofGTF2I, was sufficient to rescue ASD-like phenotypes. We propose that the GTF2I-LSD1 axis constitutes a molecular pathway amenable to therapeutic intervention.
Increased public health threat of avian-origin H3N2 influenza virus during evolution in dogs
Authors: Chen Mingyue , Lyu Yanli , Wu Fan , Zhang Ying , Li Hongkui , Wang Rui , Liu Yang , Yang Xinyu , Zhou Liwei , Zhang Ming , Tong Qi , Sun Honglei , Pu Juan , Liu Jinhua , Sun Yipeng
Published: October 2022

Influenza A viruses in animal reservoirs repeatedly cross species barrier to infect humans. Once an animal-borne virus with novel antigenicity acquired the efficient human to human transmissibility, it will become epidemic in the population. Dogs are the closest animal companions to humans and canine respiratory tract expresses both SAα2,3-(avian type) and α2,6-Gal (human type) receptors. However, the role of dogs in the ecology of influenza viruses is unclear. H3N2 avian influenza viruses transmitted to dogs around 2006 and have formed stable lineages. The long-term epidemic of avian-origin H3N2 virus in canine offers the best models to investigate the effect of dogs on the evolution of influenza viruses. Here, we carried out a systematic and comparative identification of the biological characteristics of H3N2 canine influenza viruses (CIVs) isolated in the worldwide over 10 years. We found that during the adaptation of H3N2 CIVs to dogs, H3N2 CIVs became to recognize the human-like SAα2,6-Gal receptor, gradually increased HA acid stability and replication ability in human airway epithelial cells, and acquired a 100% transmission rate via respiratory droplet in ferret model, which were essential hallmarks of being adapted to humans. We also identified that the frequency of substitutions related to human adaptation has gradually increased in H3N2 CIVs, and determined four cumulative molecular changes responsible for the increased airborne transmission ability in ferrets. Our results suggested that canine may serve as an intermediate for the adaptation of avian influenza virus to human. Continuous surveillance coordinated with risk assessment for CIVs is necessary.
Restricted effects of the soleC. elegansDaughterless/E homolog, HLH-2, on nervous system development
Authors: Masoudi Neda , Schnabel Ralf , Yemini Eviatar , Leyva-Díaz Eduardo , Hobert Oliver
Published: October 2022

Are there common mechanisms of neurogenesis used throughout an entire nervous system? Making use of the well-defined and relatively small size of the nervous system of the nematodeC. elegans, we explored to what extent canonical proneural class I/II bHLH complexes are responsible for neurogenesis throughout the entireC. elegansnervous system. Distinct, lineage-specific proneural “class II” bHLH factors are generally thought to operate via interaction with a common, “class I” bHLH subunit, encoded by Daugtherless in flies, the E (E2A, E2-2, HEB) proteins in vertebrates, andhlh-2inC. elegans. To eliminate function of all proneuronal class I/II bHLH complexes, we therefore genetically removed maternal and zygotichlh-2gene activity. We observed broad effects on neurogenesis, but still detected normal neurogenesis in many distinct neuron-producing lineages of the central and peripheral nervous system. Moreover, we find thathlh-2selectively affects some aspects of neuron differentiation while leaving others unaffected. While our studies confirm the function of proneuronal class I/II bHLH complexes in many different lineages throughout a nervous system, we conclude that their function is not universal, but rather restricted by lineage, cell type and components of differentiation programs affected.
A new QEXAFS system on the general XAFS beamline at the Shanghai Synchrotron Radiation Facility
Authors: Zhou Yongnian , Gu Songqi , Zhao Ying , Jiang Zheng , Zhang Zhaohong
Published: October 2022

A new quick-scanning extended X-ray absorption fine-structure (QEXAFS) system for in situ studies has been developed and tested on the general XAFS beamline at the Shanghai Synchrotron Radiation Facility. In the new system, an analog-to-digital converter (ADC) with 1 MHz sampling rate is used to acquire the detector data while one scaler is used to precisely calculate the scanning energy. Two external hardware trigger signals were adopted to synchronize the data collection of the ADC and the scaler. The software development platforms of the double-crystal monochromator control system and the new QEXAFS system have been unified with the Experimental Physics and Industrial Control System. By comparing the spectra acquired by the conventional step-by-step XAFS system with an energy range of 1200 eV at the 7.5um Cu foil K-edge, the new system demonstrates satisfactory signal-to-noise ratio and energy resolution. The previous shortcomings, including distortion of the spectrum and energy shift, have been overcome. The tests with different integration times indicated that appropriate parameters not only ensure good experimental results but also enhance the smoothness of the XAFS spectrum at high energy zones. The reliability of the new system has also been verified.
Adaptive mesh refinement for finite element analysis of the free vibration disturbance of cylindrical shells due to circumferential micro-crack damage
Authors: Wang Yongliang , Hu Jiansong , Kennedy David , Wang Jianhui , Wu Jiali
Published: October 2022

Purpose

Moderately thick circular cylindrical shells are widely used as supporting structures or storage cavities in structural engineering, rock engineering, and aerospace engineering. In practical engineering, shells often work with micro-cracks or defects. The existence of micro-crack damage may result in the disturbance of dynamic behaviours and even induce accidental dynamic disasters. The free vibration frequency and mode are important parameters for the dynamic performance and damage identification analysis. In particular, stiffness weakening of the local damage region leads to significant changes in the vibration mode, which makes it difficult for the mesh generated in the conventional finite element method to capture a high-precision solution of the local oscillation.

Design/methodology/approach

In response to the above problems, this study developed an adaptive finite element method and a crack damage characterisation method for moderately thick circular cylindrical shells. By introducing the inverse power iteration method, error estimation, and mesh subdivision refinement technique for the analysis of finite element eigenvalue problems, an adaptive computation scheme was constructed for the free vibration problem of moderately thick circular cylindrical shells with circumferential crack damage.

Findings

Based on typical numerical examples, the established adaptive finite element solution for the free vibration of moderately thick circular cylindrical shells demonstrated its suitability for solving the high-precision free vibration frequency and mode of cylindrical shell structures. The any order frequency and mode shape of cracked cylindrical shells under the conditions of different ring wave numbers, crack locations, crack depths, and multiple cracks were successfully solved. The influences of the location, depth, and number of cracks on the disturbance of dynamic behaviours were analysed.

Originality/value

This study can be used as a reference for the adaptive finite element solution of free vibration of moderately thick circular cylindrical shells with cracks and lays the foundation for further development of a high-performance computation method suitable for the dynamic disturbance and damage identification analysis of general cracked structures.
Resourcing remuneration committees: in the dark or on the dark side of professionalisation?
Authors: Shortland Susan , Perkins Stephen J.
Published: October 2022

Purpose

The purpose of this paper is to examine how individuals involved in top pay determination view their role and accountabilities, and capability development needs, theorised under the rubric of professionalisation.

Design/methodology/approach

A qualitative research approach draws upon in-depth interviews with non-executive directors serving on remuneration committees (Remcos), institutional investors, their external advisors, and HR reward experts.

Findings

Regulation has addressed remuneration committee resourcing implications but has yet to consider the ramifications for implied professionalisation requirements for the independent actors involved. Non-executives' and institutional investors' professional engagement is potentially hindered by the capability and capacity required for the activities involved and, for NEDs, the reward attached.

Research limitations/implications

Further research is needed to evaluate professionalisation initiatives by top pay regulators and assess their impact on executive remuneration in practice.

Practical implications

Thorough induction, tailored training, and continuous professional development are crucial to quality executive remuneration decision-taking; organisational and regulatory attention to these issues is required along with widening NED selection and recognition criteria.

Originality/value

This paper provides new knowledge on how top pay decision-takers view their role, the competencies required, and necessary professional development needed to achieve organisational competitive advantage. It reveals a potential dark side to top pay decision-taker professionalisation if individuals repurpose themselves as occupants of part-time executive roles undermining corporate executives.
Building retro-commissioning standard and policy: status quo and future directions
Authors: Lai Joseph H.K. , Lai Savannah Y.T. , Edwards David John , Hou Huiying (Cynthia)
Published: October 2022

Purpose

This paper aims to review standards on or related to retro-commissioning (RCx) and policy measures that are applicable for fostering wider adoption of RCx in existing buildings. In addition to engendering broader polemic debate to address the respective gap in the prevailing body of green building knowledge, the research outcome signposts future directions of works required for developing the needed standard and policy.

Design/methodology/approach

Following an integrative review approach, RCx-related literature, statutes, publications of public and professional organizations and standards published by institutions including the International Organization for Standardization and other peer organizations in the USA, the UK, Canada and Germany were reviewed.

Findings

Cities such as Hong Kong and New York in the world’s two largest economies (China and the USA) have been proactive in the pursuit of energy-efficient buildings. Various US cities have imposed statutory requirements on RCx. The need for an international standard on RCx and a bespoke policy for driving the uptake of RCx was also identified.

Research limitations/implications

Drawn from the research includes the need for further policy research studies to direct how an appropriate policy could be established to engender wider RCx adoption internationally.

Practical implications

Practical implications center on the identified need to develop a specific standard of RCx works. Making such a standard available to facilities management practitioners is pivotal to realizing the goal of green buildings.

Originality/value

This study provides new insights, especially the future directions in developing bespoke RCx standards and policy for greening the existing buildings.