bluuebunny/crossref_metadata_2025 huggingface dataset:
A Review of Sotagliflozin: The First Dual SGLT-1/2 Inhibitor
Authors: Siddiqui Zoya , Rasouli Niloofar , Felder Eliana , Frishman William H.
Published: July 2024

Sotagliflozin (trade name INFEPA) is a novel dual sodium-glucose cotransporter-1 and -2 (SGLT-1/2) inhibitor that was developed by Lexicon Pharmaceuticals. It has emerged as a promising therapy for managing heart failure and other cardiovascular complications associated with type 2 diabetes mellitus (T2DM). Its dual inhibition of SGLT-1 and SGLT-2 receptors uniquely decreases glucose absorption in the intestine in addition to decreasing renal glucose reabsorption, leading to improved glycemic control and cardio-reno protection. Clinical trials have demonstrated its efficacy in reducing cardiovascular death, heart failure hospitalizations, and urgent visits, particularly in T2DM patients with chronic kidney disease (CKD). The drug was approved in 2023 by the Food and Drug Administration for reducing cardiovascular death and heart failure in T2DM patients with CKD and those with heart failure, irrespective of diabetic status or ejection fraction. However, despite its considerable therapeutic potential, sotagliflozin does pose notable adverse effects, including diabetic ketoacidosis, genital infections, and diarrhea. As a result, it has faced regulatory challenges in certain regions, notably the United States. The Food and Drug Administration has so far withheld approval for sotagliflozin in the treatment of type 1 diabetes due to concerns about its safety profile, specifically the risk of diabetic ketoacidosis, although Lexicon Pharmaceuticals plans to submit another new drug application for this use in 2024. Further investigation and clinical trials are warranted to fully elucidate sotagliflozin’s impact on diabetes and CKD.
Minimally Invasive Injectable Cosmetic Procedures Increase Feelings of Authenticity
Authors: Martinez Michael J. , White Michael W. , Bailey Erica R. , Smeallie Eleanor , Hoffman Lauren , You Janet , Chapas Anne M. , Lee Nayoung , Iyengar Sheena , Rieder Evan A.
Published: July 2024

BACKGROUND

Minimally invasive cosmetic dermatology procedures continue to be increasingly popular; however, the extant literature has poorly documented the psychological antecedents of interest in cosmetic procedures and their psychological consequences.

OBJECTIVE

To better inform dermatologists on their patients' motivations for cosmetic enhancement.

MATERIALS AND METHODS

In a general population survey, an online representative sample of 984 Americans reported the extent to which they feel authentic using the validated authenticity scale and whether they were interested in undergoing a cosmetic procedure. In a prospective dermatology office survey, 102 participants reported their feelings of authenticity immediately before and 2 weeks after receiving a minimally invasive injectable cosmetic procedure.

RESULTS

In the general population survey, participants interested in cosmetic procedures felt significantly less authentic than participants who were not interested (p = .003). In the prospective dermatology office survey, participants felt significantly more authentic 2 weeks after their minimally invasive injectable cosmetic procedure than before (p = .018).

CONCLUSION

Lower feelings of authenticity are associated with interest in cosmetic procedures. Participants felt more authentic 2 weeks after receiving a minimally invasive injectable cosmetic procedure. Cosmetic procedures may present patients with an opportunity to feel more like their real, genuine selves.
Effects of axis-flip of the refractive cylinder on vision and patient-reported outcome measures after toric intraocular lens implantation
Authors: Naderi Khayam , Jameel Ashmal , Chow Isabelle , Hull Chris , O'Brart David
Published: July 2024

Purpose:

To investigate the effects of cylinder axis-flip after toric intraocular lens (TIOL) implantation on vision and patient-reported outcome measures (PROMs).

Setting:

Teaching hospital in the United Kingdom.

Design:

Post hoc analysis of data from patients who participated in a prospective randomized study of TIOLs.

Methods:

Axis-flip was defined as a change in postoperative refractive cylinder (RC) axis of 90 ± 22.5 degrees from the preoperative biometric axis. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), residual RC, and CATPROM-5 and EQ-5D-3L quality-of-life scores were analyzed.

Results:

At 6 months, axis-flip occurred in 29 (34.5%) of 84 eyes of which 28 had with-the-rule (WTR) astigmatism preoperatively. Mean (±SD) UDVA (logMAR) was 0.13 (0.16) in flipped cases (FCs) and 0.10 (0.14) in unflipped cases (UFs) (P = .88). CDVA was 0.01 (0.11) in FC and was 0.00 (0.09) in UF (P = .68). Mean RC was 0.74 diopters (D) (0.41) in FC and 0.93 D (0.47) in UF (P = .08). Mean CATPROM-5 score was −6.22 (2.56) in FC and −5.52 (3.03) in UF (P = .29). Mean EQ-5D-3L calibrated score was 0.89 (0.19) in FC and 0.85 (0.19) in UF (P = .35). Retrospectively applying coefficients of adjustment to account for posterior corneal astigmatism (PCA) suggested that 6 eyes (21%) of FC with WTR might have avoided axis-flip.

Conclusions:

Axis flipping after TIOL implantation did not adversely influence visual acuity or PROMs scores. Most FC had WTR preoperatively. Adjusting for PCA might have reduced axis-flip in some of these eyes.
The Impact of Video Calling Between Preterm Infants and Their Mothers on the Physiological Parameters of Infants and Mother-Infant Bonding
Authors: Kaynak Serap , Yilmaz Hatice Bal
Published: July 2024

Purpose:

This study aimed to determine the effect of video calling between preterm infants treated in the neonatal intensive care unit (NICU) and their mothers on the physiological parameters of infants and mother-infant bonding.

Background:

Preterm infants need prolonged treatment in the NICU, and their families may have difficulty seeing their babies during this treatment process.

Methods:

This is a prospective, randomized-controlled, experimental study. The study sample consisted of 75 preterm infants and their mothers. The data were collected using a maternal introductory information form, a preterm infant introductory information form, a preterm infant physiological parameters follow-up form, and the Mother-Infant Bonding Scale (MIBS). The study included 3 study groups: the video call group, the video call with lullaby group, and the control group. Video calls between preterm infants and their mothers were made through Zoom for 5 to 10 minutes daily for 7 days. The mothers filled out the MIBS online before and on the 7th and 30th days of the study.

Results:

Preterm infants in the video call and the video call with lullaby groups had higher MIBS mean scores on the 7th and 30th days of the study than their pretest MIBS scores. Preterm infants in the video call and the video call with lullaby groups had statistically significantly higher MIBS mean scores on the seventh day of the study than those in the control group. At the end of the 7-day study period, there was an improvement in the physiological parameters of preterm infants in the video call group and the video call with lullaby group compared with those in the control group, and this relationship was statistically significant.

Conclusions:

In conclusion, the implementation of video calls between mothers and preterm infants in NICUs had a healing effect on the physiological parameters of preterm infants and increased mother-infant bonding.
Regulation of the p53/SLC7A11/GPX4 Pathway by Gentamicin Induces Ferroptosis in HEI-OC1 Cells
Authors: Li Yingying , Xu Hui , Shi Jinping , Li Cong , Li Mengxin , Zhang Xiaoling , Xue Qing , Qiu Jingjing , Cui Limei , Sun Yan , Song Xicheng , Chen Liang
Published: July 2024

Background

Gentamicin is a commonly used aminoglycoside antibiotic, with ototoxicity as a significant side effect. Ferroptosis, an iron-dependent form of cell death, has been implicated in a variety of disorders. Whether ferroptosis impacts gentamicin ototoxicity is not yet known. The current work used an in-vitro model to examine the influence of gentamicin-induced ferroptosis on cochlear hair cell damage and probable molecular biological pathways.

Methods

House Ear Institute-Organ of Corti 1 (HEI-OC1) cells were treated with different concentrations of gentamicin for 24 hours, with or without ferrostatin-1 pretreatment, to observe gentamicin-induced ferroptosis. The role of p53/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling in gentamicin-induced ferroptosis was explored by pretreating cells with the p53 inhibitor pifithrin-α (PFT-α). We investigated the effect of gentamicin on cells by assessing cell viability. Cellular proteins were isolated and Western blots were performed to detect changes in the expression of p53, SLC7A11, and GPX4. Fluorescence staining was used to assess levels of reactive oxygen species. An enzymatic detection kit was used to detect glutathione, Fe, and malondialdehyde markers.

Results

Gentamicin reduced cell viability, glutathione content, and SLC7A11 and GPX4 protein levels, and increased levels of p53 protein, reactive oxygen species, malondialdehyde, and Fe. These effects were largely blocked by pretreatment with ferrostatin-1. Pretreatment with the p53 inhibitor PFT-α prevented the gentamicin-induced reduction in SLC7A11 and GPX4, which alleviated several features of ferroptosis including glutathione depletion, iron overload, and lipid peroxidation build-up.

Conclusion

Gentamicin induces ferroptosis in the HEI-OC1 cell line, and the mechanism may be related to the p53/SLC7A11/GPX4 signaling pathway.
The Pathology of Pulmonary Disease After Pediatric Hematopoietic Stem Cell Transplantation
Authors: Cortes-Santiago Nahir , Deutsch Gail , Patel Kalyani R. , Silva-Carmona Manuel , Henderson Carolyn , Sartain Sarah E. , Bhar Saleh , Pogoriler Jennifer
Published: July 2024

Pulmonary complications continue to cause significant morbidity and mortality in posthematopoietic stem cell transplantation (HSCT) settings. The histopathology of pulmonary diseases in the post-HSCT context is poorly characterized, especially in the pediatric population. We sought to characterize the pathologic spectrum of pulmonary disease post-HSCT in a pediatric cohort. Fifty-six specimens, including 53 biopsy specimens, corresponding to 53 patients, were identified. Biopsy slides were reviewed and assigned to diagnostic categories (infectious, graft-versus-host disease, vasculopathy, indeterminate, and others) by consensus among 3 pediatric pulmonary pathologists, taking into consideration pathologic, clinical, radiologic, and laboratory findings. The most common diagnostic category was infection (n=20). Vasculopathy, mostly in the form of fibromyxoid intimal expansion, was very common in the entire cohort (n=26) and was the sole finding in a small subset of patients (n=5), with particularly poor outcomes. A subset of biopsies remained indeterminate (n=10), and the findings in this cohort were dominated by acute lung injury. The latter group had a poor prognosis, with a short biopsy-to-death interval. The overall clinicopathologic concordance was 40%, most commonly agreeing in the infectious category. Finally, wedge biopsies led to a change in management in 69% of cases versus 23% of limited procedures (i.e., core needle biopsies). Our results suggest that while infectious complications continue to be common post-HSCT, other findings such as vasculopathy and acute lung injury portend a particularly poor prognosis and should be actively sought and reported.
Exploring the Efficacy of a Dynamic Harness System on Gross Motor Development and Motivation for Infants With Down Syndrome: A Pilot Study
Authors: Abuatiq Reham A. , Hoffman Mia E. , LaForme Fiss Alyssa , Looper Julia , Feldner Heather A.
Published: July 2024

Purpose:

To explore the benefits of a Partial Body Weight Support (PBWS) harness system within a play enriched environment on gross motor development and mastery motivation of infants with Down Syndrome (DS).

Methods:

A randomized crossover study with 17 pre-walking infants with DS in two conditions—play with or without the harness engaged—each for 3×/week over 3 weeks with a 1-week washout. Assessments took place at baseline, crossover, and completion.

Results:

Statistically and clinically significant changes were evident on the Gross Motor Function Measure-88; however, there were no significant changes in parent-reported mastery motivation.

Conclusion:

The combination of PBWS harness system support and high frequency-facilitated play within an enriched play environment positively affected gross motor development. The intervention did not impact mastery motivation skills, and the direct impact of the harness remains unclear.
Integrating Heart Rate Monitoring Into a Camp for Children With Neuromotor Disorders: A Case Series
Authors: Rubsam Meaghan , Hohl Kristen , Smaller Kevin , Lopez Gabriela , Rafferty Miriam
Published: July 2024

Purpose:

This case series investigated the implementation fidelity, feasibility, and effectiveness of integrating continuous heart rate monitoring with visual feedback into an established, intensive physical therapy camp for children with neuromotor disorders.

Summary of Key Points:

The provision of continuous visual feedback through color-coded, individually calculated heart rate zones was a feasible and effective intervention, encouraging pediatric gait camp participants to exercise at intensities that produced aerobic and functional gains. The use of technology facilitated participation with peers, an outcome equally as important as their endurance and functional improvements.

Conclusions and Recommendations for Clinical Practice:

Pediatric physical therapists play a crucial role in enhancing the well-being and physical fitness of children with disabilities. Encouraging regular exercise in a social environment fosters enjoyable, inclusive experiences while promoting overall health. It is important for clinicians in various pediatric rehabilitation settings to establish programs that offer such opportunities for children with neuromotor disorders.
Clinical Effect of Combined Fascia Sheath Suspension With Shortening Levator Muscle on Severe Blepharoptosis
Authors: Wei Ranran , Ding Kun , Zhang Shan , Cao Zhe , Liang Xiaoqin
Published: July 2024

Objective:

To study the clinical effect of conjoint fascial sheath (CFS) suspension and levator palpebrae superioris muscle shortening in the treatment of severe blepharoptosis.

Methods:

Forty-five patients with severe blepharoptosis (75 eyes) from May 2020 to February 2022 in the authors' hospital were divided into 2 groups: group A (n = 33, 43 eyes) and group B (n = 24, 32 eyes). Group A was operated on by CFS + levator muscle shortening, and group B was operated on by frontal muscle flap suspension + levator muscle shortening. Both groups were followed up for 12 months (until February 2023). The clinical effect was counted in 6 months after operation, the early complications were counted in 1 month after operation, and the late complications were counted in 1 month to 12 months after operation. Margin to corneal reflex distance 1 (MRD1) and palpebral fissure height (PFH) were recorded before, 1 week, 3 months, and 12 months postoperatively, and the amount of eyelid retrogression was counted again.

Results:

The good correction rate was 90.70% in group A, higher than in group B (71.88%), and the difference was statistically significant (P < 0.05); the early postoperative complication rate was 9.30%, lower than in group B (24.38%), and the difference was statistically significant (P < 0.05); the late postoperative complication rate was 2.33%, lower than group B (18.75%), and the difference was statistically significant (P < 0.05). The MRD1 and PFH of group A were higher than those of group B (P < 0.05) at 3 months postoperatively and 12 months postoperatively; the MRD1 and PFH of group A were lower than those of group B (P < 0.05) at 3 months postoperatively and 12 months postoperatively. Repeated measurement analysis of variance showed that there were significant differences in the main effects of MRD1, PFH, eyelid retrogression, and time in group A and group B (P < 0.05), and there was interaction between intervention and time (P < 0.05).

Conclusion:

Conjoint fascial sheath suspension combined with levator palpebrae superioris muscle shortening can effectively improve MRD1 and PFH, and the amount of upper eyelid retraction is controllable 1 year after operation.
Improving Surgical Care and Outcomes in Older Cancer Patients Through Implementation of a Presurgical Toolkit (OPTI-Surg)—Final Results of a Phase III Cluster Randomized Trial (Alliance A231601CD)
Authors: Chang George J. , Gunn Heather J. , Barber Anne K. , Lowenstein Lisa M. , Dohan Daniel , Broering Jeanette , Dockter Travis , Tan Angelina D. , Dueck Amylou , Chow Selina , Neuman Heather , Finlayson Emily ,   on behalf of the OPTI-Surg Investigators
Published: July 2024

Objective:

To assess the effect of a practice-level preoperative frailty screening and optimization toolkit (OPTI-Surg) on postoperative functional recovery and complications in elderly cancer patients undergoing major surgery.

Background:

Frailty is common in older adults. It increases the risk of poor postoperative functional recovery and complications. The potential for a practice-level screening/optimization intervention to improve outcomes is unknown.

Methods:

Thoracic, gastrointestinal, and urologic oncological surgery practices within the National Cancer Institute Community Oncology Research Program (NCORP) were randomized 1:1:1 to usual care (UC), OPTI-Surg, or OPTI-Surg with an implementation coach. OPTI-Surg consisted of the Edmonton Frail Scale and guided recommendations for referral interventions. Patients 70 years old or above undergoing curative intent surgery were eligible. The primary outcome was 8 weeks postoperative function (kcal/wk). The key secondary outcome was complications within 90 days. Mixed models were used to compare UC to the 2 OPTI-Surg arms combined.

Results:

From July 2019 to September 2022, 325 patients were enrolled in 29 practices. One hundred ninety-nine (64 UC, 135 OPTI-Surg) and 279 (78 UC, 201 OPTI-Surg) were evaluable for primary and secondary analysis, respectively. UC and OPTI-Surg patients did not significantly differ in total caloric expenditure (2.2 UC, 2.0 OPTI-Surg) after adjusting for baseline function (P=0.53). UC and OPTI-Surg patients did not significantly differ in postoperative complications (25.6% UC, 35.3% OPTI-Surg, P=0.5).

Conclusions:

Frailty assessment was successfully performed, but the OPTI-Surg intervention did not improve postoperative function nor reduce postoperative complications compared with UC. Future analysis will explore practice-level factors associated with toolkit implementation and the differences between the coaching and noncoaching arms.
Urinary Incontinence Care-Seeking Barriers Among Latina Patients: What Are We Missing?
Authors: Pancheshnikov Anna , Harrington Bryna J. , Handa Victoria L. , Yanes Liz I. , Le Neveu Margot , Voegtline Kristin M. , Olson Sarah B. , Blomquist Joan L. , Jacobs Stephanie , Patterson Danielle , Chen Chi Chiung Grace
Published: July 2024

Importance

The Latina population is the largest growing ethnic group in the United States with high levels of health disparities in urinary incontinence (UI) treatment and complications rates, which may be due to disproportionately high barriers to UI care-seeking among Latinas.

Objectives

The objectives of this study were to compare barriers to UI care-seeking among Latina, non-Latina Black, and non-Latina White patients by utilizing the Barriers to Incontinence Care Seeking Questionnaire (BICS-Q) total scores, and to compare specific barriers utilizing BICS-Q subscales.

Study Design

In this cross-sectional study, patients accessing primary care were recruited to complete the BICS-Q, International Consultation on Incontinence Questionnaire–Short Form, and Prolapse and Incontinence Knowledge Questionnaire–Urinary Incontinence. The BICS-Q total and subscale scores were compared among ethnic/racial groups.

Results

A total of 298 patients were included in the study with 83 Black, 144 Latina, and 71 White participants per self-identified ethnicity/race. The total BICS-Q score was highest for Latina participants, followed by White and Black participants (11.2 vs 8.2 vs 4.9, respectively, P < 0.0001). Latina participants had significantly higher BICS-Q subscale scores compared with Black participants with no significant differences between Latina and White participants. After controlling for potential confounders, Latina ethnicity/race was still associated with a higher BICS-Q score when compared to Black ethnicity/race (P = 0.0077), and lower Prolapse and Incontinence Knowledge Questionnaire–Urinary Incontinence scores remained independently associated with higher BICS-Q scores (P = 0.0078).

Conclusions

In our study population, Latina patients and patients with lower UI knowledge experience higher barriers to UI care-seeking compared with Black patients and patients with higher UI knowledge. Addressing these barriers may increase care-seeking and improve health equity in the field.
Effects of interfacial debonding on the stability of finitely strained periodic microstructured elastic composites
Authors: Greco Fabrizio , Luciano Raimondo , Pranno Andrea
Published: July 2024

Predicting failure initiation in nonlinear composite materials, often referred to as metamaterials, is a fundamental challenge in nonlinear solid mechanics. Microstructural failure mechanisms encompass fracture, decohesion, cavitation, compression-induced contact and instabilities, affecting their unconventional static and dynamic performances. To fully take advantage of these materials, especially in extreme applications, it is imperative to predict their nonlinear behaviour using reliable, accurate and computationally efficient numerical methodologies. This study presents an innovative nonlinear homogenization-based theoretical framework for characterizing the failure behaviour of periodic reinforced hyperelastic composites induced by reinforcement/matrix decohesion and interaction between contact mechanisms and microscopic instabilities. Debonding and unilateral contact between different phases are incorporated by employing an enhanced cohesive/contact model, which features a special nonlinear interface constitutive law and an accurate contact formulation within the context of finite strain continuum mechanics. The theoretical formulation is demonstrated using periodically layered composites subjected to macroscopic compressive loading conditions along the lamination direction. Numerical results illustrate the ways in which debonding phenomena, in conjunction with fibre microbuckling, may influence the critical loads of the examined composite solid. The sensitivity of the results obtained through the proposed contact–cohesive model at finite strain with respect to its implementation is also explored.

This article is part of the theme issue ‘Current developments in elastic and acoustic metamaterials science (Part 1)’.
Active mechanical cloaking for unsupervised damage resilience in programmable elastic metamaterials
Authors: Kundu D. , Naskar S. , Mukhopadhyay T.
Published: July 2024

Owing to the architected void-filled low-density configurations, metamaterials are prone to defects during the complex manufacturing process, or damages under operational conditions. Recently mechanical cloaking has been proposed to shield the effect of such disorders in terms of homogenized mechanical responses. The major drawback in these studies are that the damage location should be known
a priori
, and the cloak is designed around that damaged zone before manufacturing. Such postulation does not allow unsupervised damage resilience during the manufacturing and service life of metamaterials by active reconfiguration of the stress field depending on the random and unpredictable evolution of damage. Here, we propose a radically different approach by introducing piezoelectric lattices where the effect of random appearance of any single or multiple disorders and damages with complex shapes, sizes and distributions can be shielded through active multi-physically controlled cloaks by voltage-dependent modulation of the stress fields within the cloaking region. Notably, this can be achieved without breaking periodicity and any additional material in the cloaking region unlike earlier studies concerning mechanical cloaks. The proposed active class of elastic metamaterials will bring a step-change in the on-demand mechanical performance of critically important structural components and unsupervised damage resilience for enhanced durability and sustainability.

This article is part of the theme issue ‘Current developments in elastic and acoustic metamaterials science (Part 1)’.
Elastic metasurfaces for Scholte–Stoneley wave control
Authors: Zeighami Farhad , Quqa Said , De Ponti Jacopo Maria , Ayyash Nadeen , Marzani Alessandro , Palermo Antonio
Published: July 2024

In this work, we investigate the dynamics of Scholte–Stoneley waves (SSWs) travelling along elastic metasurfaces, e.g. thin resonant structures embedding mechanical oscillators, placed at the interface between solid and fluid. To this purpose, an analytical dispersion law, valid in the long-wavelength regime, is derived and used to reveal the hybridization of SSWs with the collective resonance of the mechanical oscillators and the conversion of SSWs into leaky modes within the fluid. The analytical predictions are validated through numerical simulations that include both dispersive and harmonic analysis. Our findings disclose the capabilities of elastic metasurfaces in filtering, trapping and converting SSWs along fluid–solid interfaces, thus supporting the design of novel devices for solid–fluid interaction across various engineering applications, including microfluidics.

This article is part of the theme issue 'Current developments in elastic and acoustic metamaterials science (Part 1)'.
Surface wave mitigation by periodic wave barriers under a moving load: theoretical analysis, numerical simulation and experimental validation
Authors: Ni Yu , Shi Zhifei
Published: July 2024

Periodic wave barriers (PWB) open a new window for vibration mitigation. However, the Doppler effect is rarely considered in most of the previous investigations on the control of ambient vibration induced by moving loads. This article reveals the significance of the speed and frequency of moving loads on surface waves, and improves the design method of PWB for ambient vibration reduction and isolation. First, the theoretical expression of the main frequency band of surface waves propagating in an elastic half-space caused by a moving load was obtained. Comparisons with the numerical results under three different types of traffic loads were also conducted and good agreement was found. Second, the theoretical expression and numerical results were verified by experimental studies. Some inherent properties of wave propagation caused by a moving load in an elastic half-space were also revealed. Third, two kinds of PWBs, i.e. periodic empty trench barrier and periodic pile barrier, were introduced to mitigate wave propagation. It has been confirmed that if the attenuation zones of PWB match the target frequency bands given by the theoretical expression, good vibration mitigation can be achieved.

This article is part of the theme issue ‘Current developments in elastic and acoustic metamaterials science (Part 1)’.
Elastic wave control in reticulated plates using Schwarz primitive cells
Authors: Hejazi Nooghabi Aida , Thomsen Henrik R. , Zhao Bao , Colombi Andrea
Published: July 2024

In this work, the Schwarz primitive unit cell is used as the building block of different types of metastructures for steering and focusing elastic vibrations. The emergence of a Bragg-type bandgap when constructing a two-dimensional plate from such unit cells is experimentally validated. It is demonstrated that increasing both mass and porosity of the Schwarz primitive leads to a decrease in the frequency of the out-of-plane propagating wave targeted in this study. By arranging these modified Schwarz primitive unit cells in constant and graded layouts, two-dimensional plates with an embedded metabarrier and a metalens are numerically designed. The metabarrier protects an interior area of the plate from the propagating waves on a wide frequency band (approx. 1.4–3.4 kHz). Equally, the refractive index profile necessary for gradient index lenses is obtained via a progressive variation of the added mass or, alternatively, the porosity of the unit cell over a rectangular area. For the first time, bending of the out-of-plane mode towards the focusing point is practically validated in a challenging mesoscale experiment requiring the assembly of different three-dimensional printed sections of the plate. The increased porosity design is advantageous not only in terms of overall lightweight, but also towards additive manufacturing as it requires less material.

This article is part of the theme issue ‘Current developments in elastic and acoustic metamaterials science (Part 1)’.
Episode-specific and common intrinsic functional network patterns in bipolar
Authors: Liu Xiaobo , Liu Zhen-Qi , Wan Bin , Zhang Xihan , Liu Lang , Xiao Jinming , Meng Yao , Liu Xiaoqiang , Wang Sanwang , Weng Chao , Gao Yujun
Published: July 2024

Understanding the alterations in brain function across different episodes of bipolar disorder (BD), including manic (BipM), depressive (BipD), and remission states (rBD), poses a significant challenge. In our cross-sectional study, we collected resting-state functional magnetic resonance imaging data from 117 BD patients (BipM: 38, BipD: 42, rBD: 37) and 35 healthy controls. Our aim was to delineate functional connections associated with episode dynamics, delineate common and specific patterns, validate them as biomarkers, and elucidate their biological underpinnings. Initially, we identified a common altered pattern within the sub-regions of the ventral-attention network, alongside specific patterns observed in the default mode network for BipM, the prefrontal network for BipD, and the limbic network for rBD. Using large-sample data from the Human Connectome Project, we further identified that these connectivity patterns exhibit relatively high reliability and heritability. Also, these distinct patterns accurately characterized the diverse episodes of BD and effectively predicted the cor responding clinical symptoms linked with each episode type. Importantly, using out of sample data to decode possible neurobiological mechanisms underlying these patterns, we found that regions of particular interest were enriched in multiple receptors, including MOR, NMDA, and H3 for specific alterations, and A4B2, 5HTT, and 5HT1a for common alterations. Moreover, both episode-specific and common patterns demonstrated a high enrichment for cell types such as L5ET, Micro/PVM,oligodendrites and Chandelier. Our study offers novel insights concerning episode dynamics in BD, paving the way for personalized medicine approaches tailored to address the various episodes.
Environmental versus litter traits as drivers of microbial decomposer functions
Authors: Stock Svenja C. , Canessa Rafaella , van den Brink Liesbeth , Cavieres Lohengrin A. , Kappler Andreas , Guzmán Carolina Merino , Saldaña Alfredo , Scholten Thomas , Schweiger Andreas H. , Rehfeld Kira , Neidhardt Harald , Oelmann Yvonne , Tielbörger Katja , Bader Maaike Y. , Ehlers Todd A. , Dippold Michaela A.
Published: July 2024

Plant litter decomposition is a key ecosystem process with significant implications for global carbon cycling, soil fertility and plant productivity. Given that microbial decomposers are the main players in the decomposition process, it is surprising how little is known about their functional diversity in different habitats or their ability to respond to environmental changes. To fill this knowledge gap, we conducted a litterbag decomposition experiment along a pronounced climate and vegetation gradient in the Chilean Coastal Cordillera (26°S to 38°S), ranging from hyper-arid to temperate, using mixtures of four plant species, native to the respective ecosystems. We analyzed potential decomposition functions of bacterial and fungal litter communities along with their biotic (litter traits) and abiotic (meteorological conditions and soil properties) environments, to determine the relative importance of these environmental factors for microbial community functioning. We also tested the impact of the functional diversity of the decomposer communities (i.e., the diversity of decomposition related functions) on litter mass loss.

Functional composition was related most strongly to the temporal variation of precipitation and radiation, explaining about 19 % and 6 % of variation in bacteria and fungi, respectively. In contrast, functional diversity was quite strongly related to litter chemical traits (C:N, C:P, tannins, phenols). Litter mass loss after six months of decomposition was not correlated to the functional diversity of decomposer communities but increased with the presence of habitat generalists likeProteobacteria,Actinobacteria,Firmicutes, andBacteroidetes. Taken together, these results highlight i) the interplay between abiotic factors and chemical litter traits on litter microbial functions and functional diversity and ii) the importance of microbial generalists for litter decomposition across different ecosystems. These results enhance our ability to predict changes in microbial decomposer communities and litter decomposition under future climate-change scenarios.
Computational Screening ofZanthoxylum armatumDC Phytochemicals for inhibiting Mutant P53 in Throat Cancer Therapy
Authors: Taring Ampi , Singpho Senggam Wakhet , Lamu Lobsang , Kalita Bipul Chandra , Tag Hui , Hui Pallabi Kalita
Published: July 2024

Aim

To investigate the potential of phytochemicals fromZanthoxylum armatumDC in targeting mutant p53 as a therapeutic strategy for throat cancer using an in-silico approach.

Background

Throat cancer is increasingly associated with mutations in the TP53 gene, leading to dysfunctional p53 proteins. Current synthetic drugs targeting mutant p53 face challenges of toxicity and off-target effects, necessitating the exploration of alternative natural compounds.

Methods

We employed molecular docking, molecular dynamics simulations, MMPBSA analysis, and ADMET studies to identify and characterize effective inhibitors of mutant p53 fromZ. armatumDC phytochemicals.

Results

Three compounds – Z3, Z7, and Z33 – demonstrated superior binding affinities to mutant p53 compared to the commercial drug Prima. These phytochemicals induced more compact and stable protein conformations, with Z3 and Z7 notably restricting active site residual motion. MMPBSA analysis confirmed favourable binding energetics, while ADMET studies indicated drug-like properties with potentially lower toxicity than Prima.

Conclusion

This study provides compelling evidence for the potential ofZ. armatumDC phytochemicals, particularly Z3 and Z7, as novel therapeutic agents targeting mutant p53 in throat cancer. These findings offer a foundation for future experimental validation and drug development efforts.
Cell-intrinsic platinum response and associated genetic and gene expression signatures in ovarian cancer cell lines and isogenic models
Authors: Adams Kristin M. , Wendt Jae-Rim , Wood Josie , Olson Sydney , Moreno Ryan , Jin Zhongmou , Gopalan Srihari , Lang Jessica D.
Published: July 2024

Ovarian cancers are still largely treated with platinum-based chemotherapy as the standard of care, yet few biomarkers of clinical response have had an impact on clinical decision making as of yet. Two particular challenges faced in mechanistically deciphering platinum responsiveness in ovarian cancer have been the suitability of cell line models for ovarian cancer subtypes and the availability of information on comparatively how sensitive ovarian cancer cell lines are to platinum. We performed one of the most comprehensive profiles to date on 36 ovarian cancer cell lines across over seven subtypes and integrated drug response and multiomic data to improve on our understanding of the best cell line models for platinum responsiveness in ovarian cancer. RNA-seq analysis of the 36 cell lines in a single batch experiment largely conforms with the currently accepted subtyping of ovarian cancers, further supporting other studies that have reclassified cell lines and demonstrate that commonly used cell lines are poor models of high-grade serous ovarian carcinoma. We performed drug dose response assays in the 32 of these cell lines for cisplatin and carboplatin, providing a quantitative database of IC50s for these drugs. Our results demonstrate that cell lines largely fall either well above or below the equivalent dose of the clinical maximally achievable dose (Cmax) of each compound, allowing designation of cell lines as sensitive or resistant. We performed differential expression analysis for high-grade serous ovarian carcinoma cell lines to identify gene expression correlating with platinum-response. Further, we generated two platinum-resistant derivatives each for OVCAR3 and OVCAR4, as well as leveraged clinically-resistant PEO1/PEO4/PEO6 and PEA1/PEA2 isogenic models to perform differential expression analysis for seven total isogenic pairs of platinum resistant cell lines. While gene expression changes overall were heterogeneous and vast, common themes were innate immunity/STAT activation, epithelial to mesenchymal transition and stemness, and platinum influx/efflux regulators. In addition to gene expression analyses, we performed copy number signature analysis and orthogonal measures of homologous recombination deficiency (HRD) scar scores and copy number burden, which is the first report to our knowledge applying field-standard copy number signatures to ovarian cancer cell lines. We also examined markers and functional readouts of stemness that revealed that cell lines are poor models for examination of stemness contributions to platinum resistance, likely pointing to the fact that this is a transient state. Overall this study serves as a resource to determine the best cell lines to utilize for ovarian cancer research on certain subtypes and platinum response studies, as well as sparks new hypotheses for future study in ovarian cancer.
A path analysis disentangling determinants of natal dispersal in a cooperatively breeding bird
Authors: Borger Mirjam J. , Lee Kiran G.L. , Weissing Franz J. , Richardson David S. , Dugdale Hannah L. , Burke Terry , Pen Ido , Komdeur Jan
Published: July 2024

Delayed offspring dispersal is an important aspect of the evolution of cooperative breeding. By applying a path-analysis approach to the long-term Seychelles warbler (Acrocephalus sechellensis) dataset, we studied whether and how delayed dispersal is affected by territory quality, the presence of helpers and non-helping subordinates, maternal breeding status, age and fecundity, and offspring sex ratio. We found that offspring are more likely to disperse when their genetic mothers are co-breeders, helpers are absent and territory quality is high. In contrast to earlier findings, our analysis does not support the idea that offspring sex ratio is affected by territory quality and helper presence. Our findings suggest that a complex interplay of ecological and social factors shapes dispersal decisions. Our study underscores the importance of considering proximate factors in understanding cooperative breeding dynamics, and it shows that path analyses offer valuable insights into dissecting the intricate relationships influencing dispersal in wild populations.
Defining Suicidal Thought and Behavior Phenotypes for Genetic Studies
Authors: Monson Eric T. , Colbert Sarah M. C. , Andreassen Ole A. , Ayinde Olatunde O. , Bejan Cosmin A. , Ceja Zuriel , Coon Hilary , DiBlasi Emily , Izotova Anastasia , Kaufman Erin A. , Koromina Maria , Myung Woojae , Nurnberger John I. , Serretti Alessandro , Smoller Jordan W. , Stein Murray B. , Zai Clement C. ,   Suicide Working Group of the Psychiatric Genomics Consortium, Aslan Mihaela , Barr Peter B. , Bigdeli Tim B. , Harvey Philip D. , Kimbrel Nathan A. , Patel Pujan R. ,   Cooperative Studies Program (CSP) #572, Ruderfer Douglas , Docherty Anna R. , Mullins Niamh , Mann J. John
Published: July 2024

Background

Standardized definitions of suicidality phenotypes, including suicidal ideation (SI), attempt (SA), and death (SD) are a critical step towards improving understanding and comparison of results in suicide research. The complexity of suicidality contributes to heterogeneity in phenotype definitions, impeding evaluation of clinical and genetic risk factors across studies and efforts to combine samples within consortia. Here, we present expert and data-supported recommendations for defining suicidality and control phenotypes to facilitate merging current/legacy samples with definition variability and aid future sample creation.

Methods

A subgroup of clinician researchers and experts from the Suicide Workgroup of the Psychiatric Genomics Consortium (PGC) reviewed existing PGC definitions for SI, SA, SD, and control groups and generated preliminary consensus guidelines for instrument-derived and international classification of disease (ICD) data. ICD lists were validated in two independent datasets (N = 9,151 and 12,394).

Results

Recommendations are provided for evaluated instruments for SA and SI, emphasizing selection of lifetime measures phenotype-specific wording. Recommendations are also provided for defining SI and SD from ICD data. As the SA ICD definition is complex, SA code list recommendations were validated against instrument results with sensitivity (range = 15.4% to 80.6%), specificity (range = 67.6% to 97.4%), and positive predictive values (range = 0.59-0.93) reported.

Conclusions

Best-practice guidelines are presented for the use of existing information to define SI/SA/SD in consortia research. These proposed definitions are expected to facilitate more homogeneous data aggregation for genetic and multisite studies. Future research should involve refinement, improved generalizability, and validation in diverse populations.
Exploring the Single-Cell Dynamics of FOXM1 Under Cell Cycle Perturbations
Authors: Jawwad Tooba , Kamkaew Maliwan , Phongkitkarun Kriengkrai , Chusorn Porncheera , Sampattavanich Somponnat
Published: July 2024

The cell cycle is crucial for maintaining normal cellular functions and preventing replication errors. FOXM1, a key transcription factor, plays a pivotal role in regulating cell cycle progression and is implicated in various physiological and pathological processes, including cancers like liver, prostate, breast, lung, and colon cancer. Despite previous research, our understanding of FOXM1 dynamics under different cell cycle perturbations and its connection to heterogeneous cell fate decisions remains limited. In this study, we investigated FOXM1 behavior in individual cells exposed to various perturbagens. We found that different drugs induce diverse responses due to heterogeneous FOXM1 dynamics at the single-cell level. Single-cell analysis identified six distinct cellular phenotypes: on-time cytokinesis, cytokinesis delay, cell cycle delay, G1 arrest, G2 arrest, and cell death, observed across different drug types and doses. Specifically, treatments with PLK1, CDK1, CDK1/2, and Aurora kinase inhibitors revealed varied FOXM1 dynamics leading to heterogeneous cellular outcomes. Our findings affirm that FOXM1 dynamics are pivotal in determining cellular outcomes, independent of the specific inhibitor employed. Our results gave insights into how FOXM1 dynamics contribute to cell cycle fate decisions, especially under different cell-cycle perturbations.
Synaptogyrin-3 Prevents Cocaine Addiction and Dopamine Deficits
Authors: Peck Emily G. , Holleran Katherine M. , Curry Alyson M. , Holter Kimberly M. , Estave Paige M. , Sens Jonathon P. , Locke Jason L. , Ortelli Olivia A. , George Brianna E. , Dawes Monica H. , West Alyssa M. , Alexander Nancy J. , Kiraly Drew D. , Farris Sean P. , Gould Robert W. , McCool Brian A. , Jones Sara R.
Published: July 2024

Synaptogyrin-3, a functionally obscure synaptic vesicle protein, interacts with vesicular monoamine and dopamine transporters, bringing together dopamine release and reuptake sites. Synaptogyrin-3 was reduced by chronic cocaine exposure in both humans and rats, and synaptogyrin-3 levels inversely correlated with motivation to take cocaine in rats. Synaptogyrin-3 overexpression in dopamine neurons reduced cocaine self-administration, decreased anxiety-like behavior, and enhanced cognitive flexibility. Overexpression also enhanced nucleus accumbens dopamine signaling and prevented cocaine-induced deficits, suggesting a putative therapeutic role for synaptogyrin-3 in cocaine use disorder.
Characterizing microglial signaling dynamics during inflammation using single-cell mass cytometry
Authors: Kumar Sushanth , Kahle August D. , Keeler Austin B. , Zunder Eli R. , Deppmann Christopher D.
Published: July 2024

Microglia play a critical role in maintaining central nervous system (CNS) homeostasis and display remarkable plasticity in their response to inflammatory stimuli. However, the specific signaling profiles that microglia adopt during such challenges remain incompletely understood. Traditional transcriptomic approaches provide valuable insights, but fail to capture dynamic post-translational changes. In this study, we utilized time-resolved single-cell mass cytometry (CyTOF) to measure distinct signaling pathways activated in microglia upon exposure to bacterial and viral mimetics—lipopolysaccharide (LPS) and polyinosinic-polycytidylic acid (Poly(I:C)), respectively. Furthermore, we evaluated the immunomodulatory role of astrocytes on microglial signaling in mixed cultures. Microglia or mixed cultures derived from neonatal mice were treated with LPS or Poly(I:C) for 48 hrs. Cultures were stained with a panel of 33 metal-conjugated antibodies targeting signaling and identity markers. High-dimensional clustering analysis was used to identify emergent signaling modules. We found that LPS treatment led to more robust early activation of pp38, pERK, pRSK, and pCREB compared to Poly(I:C). Despite these differences, both LPS and Poly(I:C) upregulated the classical activation markers CD40 and CD86 at later time-points. Strikingly, the presence of astrocytes significantly blunted microglial responses to both stimuli, particularly dampening CD40 upregulation. Our studies demonstrate that single-cell mass cytometry effectively captures the dynamic signaling landscape of microglia under pro-inflammatory conditions. This approach may pave the way for targeted therapeutic investigations of various neuroinflammatory disorders. Moreover, our findings underscore the necessity of considering cellular context, such as astrocyte presence, in interpreting microglial behavior during inflammation.

Main Points

Time-resolved single cell mass cytometry delineates microglial signaling pathways following LPS or Poly(I:C) treatment. Astrocyte presence led to selective reduction of key microglial signaling nodes along with terminal inflammatory profiles.