bluuebunny/crossref_metadata_2025 huggingface dataset:
Bona Fide Plant Steroid Receptors are Innovated in Seed Plants and Angiosperms through Successive Whole-Genome Duplication Events
Authors: Liu Jing , Wei Qiang , Zhao Zhen , Qiang Fanqi , Li Guishuang , Wu Guang
Published: May 2024

Whole-genome duplication (WGD) events are widespread in plants and animals, thus their long-term evolutionary contribution has long been speculated, yet a specific contribution is difficult to verify. Here, we show that ɛ-WGD and ζ-WGD contribute to the origin and evolution of bona fide brassinosteroid (BR) signaling through the innovation of active BR biosynthetic enzymes and active BR receptors from their respective ancestors. We found that BR receptors BRI1 (BR INSENSITIVE 1) and BRL1/3 (BRI1-LIKES 1/3) derived by ɛ-WGD and ζ-WGD, which occurred in the common ancestor of angiosperms and seed plants, respectively, while orphan BR receptor BRL2 first appeared in stomatophytes. Additionally, CYP85A enzymes synthesizing the bioactive BRs derived from a common ancestor of seed plants, while its sister enzymes CYP90 synthesizing BR precursors presented in all land plants, implying possible ligand–receptor coevolution. Consistently, the island domains (IDs) responsible for BR perception in BR receptors were most divergent among different receptor branches, supporting ligand-driven evolution. As a result, BRI1 was the most diversified BR receptor in angiosperms. Importantly, relative to the BR biosynthetic DET2 gene presented in all land plants, BRL2, BRL1/3 and BRI1 had high expression in vascular plants ferns, gymnosperms and angiosperms, respectively. Notably, BRI1 is the most diversified BR receptor with the most abundant expression in angiosperms, suggesting potential positive selection. Therefore, WGDs initiate a neofunctionalization process diverged by ligand-perception and transcriptional expression, which might optimize both BR biosynthetic enzymes and BR receptors, likely contributing to the evolution of land plants, especially seed plants and angiosperms.
Fluid dynamics and leukocyte transit in the lymphatic system
Authors: Li Huabing , Zhang Jingjing , Padera Timothy P , Baish James W , Munn Lance L
Published: May 2024

The lymphatic system plays a vital role in maintaining fluid balance in living tissue and serves as a pathway for the transport of antigen, immune cells, and metastatic cancer cells. In this study, we investigate how the movement of cells through a contracting lymphatic vessel differs from steady flow, using a lattice Boltzmann-based computational model. Our model consists of cells carried by flow in a 2D vessel with regularly spaced, bi-leaflet valves that ensure net downstream flow as the vessel walls contract autonomously in response to calcium and nitric oxide levels regulated by stretch and shear stress levels. The orientation of the vessel with respect to gravity, which may oppose or assist fluid flow, significantly modulates cellular motion due to its effect on the contraction dynamics of the vessel, even when the cells themselves are neutrally buoyant. Additionally, our model shows that cells are carried along with the flow, but when the vessel is actively contracting, they move faster than the average fluid velocity. We also find that the fluid forces cause significant deformation of the compliant cells, especially in the vicinity of the valves. Our study highlights the importance of considering the complex, transient flows near the valves in understanding cellular motion in lymphatic vessels.
SMAD2/3-SMYD2 and developmental transcription factors cooperate with cell-cycle inhibitors to guide tissue formation
Authors: Militi Stefania , Nibhani Reshma , Pook Martin , Pauklin Siim
Published: May 2024

Tissue formation and organ homeostasis are achieved by precise coordination of proliferation and differentiation of stem cells and progenitors. While deregulation of these processes can result in degenerative disease or cancer, their molecular interplays remain unclear. Here we show that the switch of human pluripotent stem cell (hPSC) self-renewal to differentiation is associated with the induction of distinct cyclin-dependent kinase inhibitors (CDKIs). In hPSCs, Activin/Nodal/TGFβ signaling maintains CDKIs in a poised state via SMAD2/3-NANOG-OCT4-EZH2-SNON transcriptional complex. Upon gradual differentiation, CDKIs are induced by successive transcriptional complexes between SMAD2/3-SMYD2 and developmental regulators such as EOMES, thereby lengthening the G1 phase. This, in turn, induces SMAD2/3 transcriptional activity by blocking its linker phosphorylation. Such SMAD2/3-CDKI positive feedback loops drive the exit from pluripotency and stepwise cell-fate specification that could be harnessed for producing cells for therapeutic applications. Our study uncovers fundamental mechanisms of how cell-fate specification is interconnected to cell-cycle dynamics and provides insight into autonomous circuitries governing tissue self-formation.
Yet Another Lattice Formulation of 2D U(1) Chiral Gauge Theory via Bosonization
Authors: Morikawa Okuto , Onoda Soma , Suzuki Hiroshi
Published: May 2024

Recently, lattice formulations of Abelian chiral gauge theory in two dimensions have been devised on the basis of the Abelian bosonization. A salient feature of these 2D lattice formulations is that the gauge invariance is exactly preserved for anomaly-free theories and thus is completely free from the question of the gauge mode decoupling. In the present paper, we propose yet another lattice formulation sharing this desired property. A particularly unique point in our formulation is that the vertex operator of the dual scalar field, which carries the vector charge of the fermion and the “magnetic charge” in the bosonization, is represented by a “hole” excised from the lattice; this is the excision method formulated recently by Abe et al. in a somewhat different context.
Rising Security and Religious Decline: Refining and Extending Insecurity Theory
Authors: Molteni Francesco
Published: May 2024

Explaining the reasons—while not the causes—behind religious decline is a central issue for sociologists interested in secularization processes. Many theoretical perspectives have been proposed over the last decades, and this article focuses on one of them. In particular, it refers to the so-called insecurity theory, formalized by Norris and Inglehart (2011), which reads processes of religious decline in light of the increased security coming with modernization. It summarizes the empirical evidence proposed so far by distinguishing between individual and contextual insecurity and static and longitudinal approaches. Moreover, it underlines the difference between economic and existential insecurity as well as the leading role of socialization processes. From this basis, it provides a summary of the main potential weaknesses of the theory and the main criticisms leveled against it, in order to expand its theoretical relevance and clarify what insecurity theory can, and cannot, tell us about secularization processes.
Testosterone replacement therapy in patients with cachexia: a contemporary review of the literature
Authors: Tabei Seyed Sajjad , Kataria Rhea , Hou Sean , Singh Armaan , Al Hameedi Hasan , Hasan Doaa , Hsieh Mike , Raheem Omer A
Published: May 2024

Introduction

Patients with long-term chronic illnesses frequently present with hypogonadism, which is primarily managed through exogenous testosterone. These same patients also experience a high degree of cachexia, a loss of skeletal muscle and adipose tissue.

Objective

To perform a contemporary review of the literature to assess the effectiveness of testosterone replacement therapy (TRT) for managing chronic disease–associated cachexia.

Methods

We performed a PubMed literature search using MeSH terms to identify studies from 2000 to 2022 on TRT and the following cachexia-related chronic medical diseases: cancer, COPD, HIV/AIDS, and liver cirrhosis.

Results

From the literature, 11 primary studies and 1 meta-analysis were selected. Among these studies, 3 evaluated TRT on cancer-associated cachexia, 3 on chronic obstructive pulmonary disease, 4 on HIV and AIDS, and 2 on liver cirrhosis. TRT showed mixed results favoring clinical improvement on each disease.

Conclusions

Cachexia is commonly observed in chronic disease states. Its occurrence with hypogonadism, alongside the shared symptoms of these 2 conditions, points toward the management of cachexia through the administration of exogenous testosterone. Robust data in the literature support the use of testosterone in increasing lean body mass, improving energy levels, and enhancing the quality of life for patients with chronic disease. However, the data are variable, and further studies are warranted on the long-term efficacy of TRT in patients with cachexia.
Initial leadership concerns and availability of tobacco cessation services moderate changes in employee-reported concerns about tobacco-free workplace policy implementation over time
Authors: Siddiqi Ammar D , Carter Brian J , Chen Tzuan A , Martinez Leal Isabel , Britton Maggie , Correa-Fernández Virmarie , Rogova Anastasia , Kyburz Bryce , Williams Teresa , Reitzel Lorraine R
Published: May 2024

Tobacco-free workplace policies (TFWPs) are underused evidence-based interventions that reduce the elevated use of tobacco among substance use treatment center (SUTC) employees and patients. SUTC employees’ anticipated concerns about stakeholder pushback are barriers to TFWP adoption. Examination of discrepancies between anticipated and actualized employee-reported TFWP concerns arising from coworkers, patients, and community members in the context of leadership concerns and tobacco cessation care availability for employees may inform strategies to increase TFWP uptake. This study analyzed changes in employee-reported TFWP concerns from before to after a comprehensive tobacco-free workplace intervention that included TFWP implementation, using Chi-square/Fisher’s exact tests. Preimplementation leadership policy concerns and tobacco cessation care availability were examined as moderators in generalized linear mixed models. Overall, 452 employees and 13 leaders provided data from 13 SUTCs collectively serving >82 000 patients annually. Results revealed significant decreases over time in employee-reported concerns about TFWP resistance from coworkers. Moderation analyses indicated that employee-anticipated concerns from coworkers and patients, respectively, were less likely to be actualized in SUTCs where leadership endorsed preimplementation TFWP concerns, whereas employee-reported patient concerns rose over time in SUTCs where leadership had no initial implementation concerns. Additionally, employee-anticipated concerns from coworkers were overestimated in SUTCs that did not offer tobacco cessation care to employees. Results supporting the nonactualization of anticipated employee concerns following TFWP implementation can be used to engage other SUTCs for TFWP adoption. Furthermore, moderation effects may suggest that center characteristics translate to greater attention to rollout, ultimately enhancing TFWP stakeholder acceptance.
The paradox of Picroside II: As a natural antioxidant, but may instead futher aggravate liver injury by exacerbating mitochondrial oxidative stress
Authors: Yifan Xu , Jingfeng Huang , Huichuan Zhuang , Junqian Lin , Zhenzhou Jiang , Lixin Sun , Xin Huang , Luyong Zhang , Tao Wang
Published: May 2024

Background

Picroside II (PII), an iridoid glycoside extracted from the rhizomes and stems of the genus Picroside, exhibits pronounced hepatoprotective properties. Pre-administration of PII protects against acute liver injury caused by D-galactosamine (D-Gal), carbon tetrachloride (CCl4), and acetaminophen (APAP). This study aimed to elucidate the ramifications of PII administration subsequent to the initiation of acute hepatic injury.

Methods

Exploring the role of PII treatment in APAP-treated cell and rat models and in D-Gal and CCl4-treated rat models.

Results

In rats, APAP treatment increased serum aspartate transaminase, alanine transaminase, and alkaline phosphatase levels and decreased glutathione activity and the fluidity of the liver mitochondrial membrane. In L-02 cells, APAP exposure resulted in a decrement in membrane potential, an augmentation in the liberation of reactive oxygen species, and an acceleration of apoptotic processes. Moreover, PII pre-administration protected against D-Gal-induced acute hepatic injury and CCl4-induced chronic hepatic injury in rodent models, whereas PII administration post-injury aggravated CCl4-induced chronic hepatic injury.

Conclusions

Our results suggest that the effects of PII depend on the hepatic physiological or pathological state at the time of intervention. While PII possesses the potential to avert drug-induced acute hepatic injury through the mitigation of oxidative stress, its administration post-injury may exacerbate the hepatic damage, underscoring the critical importance of timing in therapeutic interventions.
Police Contact, Non-Suicidal Self-Injury, and Suicidal Ideation
Authors: Jackson Dylan B. , Testa Alexander , Fix Rebecca L. , Semenza Daniel C. , Nagata Jason M. , Ganson Kyle T.
Published: May 2024

Background and Objectives:

The purpose of this research is to investigate associations between police contact, non-suicidal self-injury (NSSI), and suicidal ideation (SI) among a national sample of Canadian adolescents and young adults (ages 16-30).

Methods:

Data used in this study were obtained from the Canadian Study of Adolescent Health Behaviors (N = 940), a national survey of Canadians ages 16-30.

Results:

Police contact was associated with higher odds of NSSI (OR = 1.98, 95% CI = 1.37, 2.86). Those who reported police contact with intrusion (OR = 2.39, 95% CI = 1.49, 3.38) and police contact with harassment (OR = 3.98, 95% CI = 2.30, 6.88) had higher odds of NSSI relative to respondents with no contact. Finally, any police contact was associated with higher odds of SI (OR = 1.56, 95% CI = 1.04, 2.34) and respondents experiencing police stops with harassment had higher odds of SI compared to those who had never been stopped (OR = 2.48, 95% CI = 1.45, 4.24).

Conclusions:

Distressing police contact heightens the risk of NSSI and SI among young people. Rigorous evaluation of trauma-informed, developmentally appropriate strategies for identifying and intervening on NSSI and SI following adverse police encounters should be prioritized.
Pharmacokinetic Variability of Rufinamide and Stiripentol in Children With Refractory Epilepsy: A Retrospective Study of Therapeutic Drug Monitoring From the National Epilepsy Centers in Denmark and Norway
Authors: Heger Katrine , Burns Margrete Larsen , Nikanorova Marina , Johannessen Svein I. , Johannessen Landmark Cecilie
Published: May 2024

Background:

Rufinamide and stiripentol, orphan drugs used in Lennox–Gastaut and Dravet syndromes, respectively, are antiseizure medications (ASMs), often administered to children; however, pharmacokinetic studies are lacking. The authors compared the pharmacokinetic variability of these drugs with respect to the dose, serum concentrations, comedication, age, and duration of treatment.

Methods:

Children and adolescents (<18 years) whose serum concentrations were measured were retrospectively identified from the therapeutic drug monitoring (TDM) databases at 2 national epilepsy centers in Norway and Denmark (2012–2021).

Results:

Data from 165 patients (56% boys/44% girls) treated with rufinamide and 52 patients (50% boys/50% girls) treated with stiripentol were included. For rufinamide, the median age was 10 (range 2–17) years, dose 23 (3–73) mg/d, and serum concentration 34 (3–227) µmol/L [8.1 mg/L (0.71–54.0 mg/L)]. For stiripentol, the median age was 8.5 (range 1–17) years, dose 37 (18–76) mg/d, and serum concentration 33 (4–113) µmol/L [7.7 mg/L (0.93–26.3 mg/L)]. The concomitant use of 1–9 other ASMs during the data collection was noted. Pharmacokinetic variability, calculated as the concentration/(dose/kg) ratio, ranged from 0.26 to 11.31 (µmol/L)/(mg/kg) for rufinamide and 0.17–1.52 (µmol/L)/(mg/kg) for stiripentol. The intraindividual coefficients of variation ranged widely, from 5% to 110% for rufinamide and 11%–117% for stiripentol. The treatment period was at least 5 years in 50% of patients. No statistically significant effects of age, sex, or ASM comedication were observed, possibly due to the small sample size and heterogeneous groups with variable seizure situations, comorbidities, and changes in comedication and physiology.

Conclusions:

This study demonstrates considerable pharmacokinetic variability in and between patients for both drugs and similar use in terms of age, burden of comedication and retention rates. TDM may be useful in the clinical setting to monitor and optimize treatment in this vulnerable patient group.
Management of the Drug–Drug Interactions Between Valproic Acid and Dolutegravir—A Case Study
Authors: Cattaneo Dario , Giacomelli Andrea , Calvagna Nunziata , Bonini Igor , Ridolfo Anna Lisa , Gervasoni Cristina
Published: May 2024

Objective:

Preliminary evidence shows that concomitant administration of valproic acid can reduce the exposure to dolutegravir with limited clinical impacts. Here, we describe a male living with HIV who experienced a drastic reduction in dolutegravir trough concentrations a few weeks after starting valproic acid treatment as identified by therapeutic drug monitoring. Concomitantly, pharmacists recommended a supplementation of magnesium to improve insomnia.

Case report:

A 62-year-old man with HIV on antiretroviral therapy with dolutegravir and lamivudine recently added valproic acid to clonazepam and sertraline to treat severe sleep disturbances. An 84% reduction in dolutegravir trough concentrations was observed compared with the previous outpatient visit (418 versus 2714 ng/mL), with values close to the minimum effective drug concentration (300 ng/mL). Considering this, we strongly discourage the use of magnesium.

Conclusions:

We are confident that our findings can contribute to a better understanding of the clinical problems that infectious disease physicians encounter in their daily management of people with HIV and how therapeutic drug monitoring may add value in this context. This case also highlights the importance of multidisciplinary services for the optimal management of polypharmacy in people with HIV.
Impact of Insurance Type on Access to Pediatric Surgical Care
Authors: Watson Rachel R. , Niedziela Cassi J. , Nuzzi Laura C. , Netson Rebecca A. , McNamara Catherine T. , Ayannusi Anuoluwa E. , Flanagan Sarah , Massey Gabrielle G. , Labow Brian I.
Published: May 2024

Background:

This study aimed to measure the impact of insurance type on access to pediatric surgical care, clinical and surgical scheduling decisions, provider-driven cancelations, and missed care opportunities (MCOs). We hypothesize that patients with public health insurance experience longer scheduling delays and more frequently canceled surgical appointments compared with patients with private health insurance.

Methods:

This retrospective study reviewed the demographics and clinical characteristics of patients who underwent a surgical procedure within the plastic and oral surgery department at our institution in 2019. Propensity score matching and linear regressions were used to estimate the effect of insurance type on hospital scheduling and patient access outcomes while controlling for procedure type and sex.

Results:

A total of 457 patients were included in the demographic and clinical characteristics analyses; 354 were included in propensity score matching analyses. No significant differences in the number of days between scheduling and occurrence of initial consultation or number of clinic cancelations were observed between insurance groups (P > 0.05). However, patients with public insurance had a 7.4 times higher hospital MCO rate (95% CI [5.2–9.7]; P < 0.001) and 4.7 times the number of clinic MCOs (P = 0.007).

Conclusions:

No significant differences were found between insurance groups in timely access to surgical treatment or cancelations. Patients with public insurance had more MCOs than patients with private insurance. Future research should investigate how to remove barriers that impact access to care for marginalized patients.
Proactive behaviors and health care workers: A systematic review
Authors: Lai Alden Yuanhong , Wee Kenneth Z. , Frimpong Jemima A.
Published: May 2024

Background

Proactive behaviors at work refer to discretionary actions among workers that are self-starting, change oriented, and future focused. Proactive behaviors reflect the idiosyncratic actions by individual workers that shape the delivery and experience of professional services, highlight a bottom-up perspective on workers’ agency and motivation that can influence organizational practices, and are associated with a variety of employee and organizational outcomes.

Purpose

This systematic review aims to understand the various forms of proactive behaviors in health care workers that have been studied, and how these proactive behaviors are associated with employee-level outcomes and quality of care.

Methods

Systematic review of articles published to date on proactive behaviors in health care workers.

Results

Based on the identification of 40 articles, we find that job crafting, active problem solving, voice, extra-role behaviors, and idiosyncratic deals have been investigated as proactive behaviors among health care workers. Among these, job crafting is the most commonly studied (35% of articles), and it has been conceptualized and measured in the most consistent way, including as individual- and group-level phenomena, and as organizational interventions. Studies on active problem solving, which refers to workers accepting responsibility, exercising control, and taking action around anticipated or experienced problems at work, have not been consistently investigated as a form of proactive behavior but represent 25% of the articles identified in this review. Overall, this review finds that proactive behaviors in health care is a burgeoning area of research, with the majority of studies being cross-sectional in design and published after 2010, and focused on workers’ job satisfaction as the outcome.

Practice Implications

Health care workers and managers should consider the distinct influences and contributions of proactive behaviors as ways to improve employee-level outcomes and quality of care.
Clinical Trajectories of Comorbidity Associated With Military-Sustained Mild Traumatic Brain Injury: Pre- and Post-Injury
Authors: Agimi Yll , Hai Tajrina , Gano Amanda , Stuessi Keith , Gold Joanne , Kaufman Rachael , McKinney Gary
Published: May 2024

Background and Objective:

In the US military, traumatic brain injury (TBI) is of distinct importance, at home and in the deployed setting, and is considered a “signature injury of the wars in Afghanistan and Iraq.” Since 2000, an estimated 468 424 service members (SMs) have been diagnosed with at least one TBI. We examined the clinical trajectories of a group of 18 comorbidities before and after a military-sustained mild TBI (mTBI).

Methods:

Without making assumptions on causality, a group of 18 conditions often co-occurring with mTBI were identified through literature review and TBI subject matter workgroup consensus. Using data from Military Health System Data Repository, we identified SMs whose first lifetime military mTBI occurred between October 1, 2016, and October 30, 2019. Correlation analyses were used to determine the linear relationship between comorbidities prior to and after mTBI diagnosis. Changes in the period prevalence of comorbidities was calculated.

Results:

We identified 42 018 SMs with a first lifetime military mTBI, of which 77.6% had at least one comorbidity. Identified SMs were mostly young (46.1% ages 18-24 years), male (81.4%), and White (64.1%). Up to 180 days prior to an mTBI, the most frequently identified conditions were sleep-related conditions (21.7%), headaches (19.4%), posttraumatic stress disorders (PTSDs) (17.8%), anxiety disorders (11.3%), and cervicogenic disorders (eg, cervicalgia) (10.9%). In the period following mTBI diagnosis, the prevalence of diagnosed conditions increased, especially for visual disturbances (327.2%), cognitive conditions (313.9%), vestibular conditions (192.6%), those related to headache (152.2%), and hearing (72.9%). Sleep-related conditions showed moderate positive correlation with a group of co-occurring conditions, led by cognitive conditions (ϕc = 0.50), anxiety disorders (ϕc = 0.42), PTSDs (ϕc =0.43), and headaches and related conditions (ϕc = 0.38).

Conclusion:

Results indicate that caring for SMs with mild TBI requires a holistic approach, one that considers the complex nature of SM conditions, prior to sustaining their mTBI, as well as after injury. We found a complex correlation of conditions that suggest SMs with mTBI are undergoing a multifaceted experience, one that may require the development of a targeted multidimensional clinical practice recommendation and practice.
Patient and Caregiver Satisfaction With the Brain Injury Rehabilitation: Improving the Transition Experience (BRITE) Intervention
Authors: Moore Megan , Kempthorne Leslie , Fann Jesse R. , Shulein Orli , Dams-O’Connor Kristen , Kajankova Maria , Conrick Kelsey M. , Seeliger Jodi , Hoffman Jeanne M.
Published: May 2024

Objective:

To ascertain patient and caregiver satisfaction with an individualized case management intervention to improve transition from inpatient rehabilitation care to the community after traumatic brain injury (TBI).

Setting:

Participants from 6 National Institute on Disability, Independent Living, and Rehabilitation Research-funded TBI Model Systems sites in the United States.

Participants:

Adult, English-speaking patients with TBI who had moderate-to-severe TBI and were discharged from a TBI Model Systems site and who were in the intervention arm of the Brain Injury Rehabilitation: Improving the Transition Experience pragmatic clinical trial, as well as their caregivers.

Design:

A survey of participants in the intervention arm, which included an individualized case management program administered by a TBI Care Manager (TCM) who facilitated resource connection, education, and support.

Main Measures:

Satisfaction with intervention was measured through Likert-scaled and open-ended questions. The survey was administered verbally through telephone, audio-recorded, and transcribed. Descriptive statistics were calculated for categorical variables, and content analysis was conducted for open-ended responses.

Results:

Patient and caregiver participants were satisfied with the intervention and highlighted the benefits of the interpersonal and practical support provided by the TCM. Participants identified the need for a more intensive intervention and clear expectations of the TCM role, as well as gaps in available medical and rehabilitation services in the community, as areas for improvement.

Conclusion:

Patients with TBI and their caregivers reported satisfaction with the individualized case management program in supporting their transition from inpatient rehabilitation to the community. Further research is needed to understand the impact on outcomes.
High hyperopic LASIK with reduction of corneal prolateness to control-induced spherical aberration
Authors: Salah-Mabed Imene , Debellemanière Guillaume , Rampat Radhika , Dubois Mathieu , Gatinel Damien
Published: May 2024

Purpose:

To evaluate visual outcomes of high hyperopic laser in situ keratomileusis (LASIK), using corneal aspherization to control the induced spherical aberration.

Setting:

Fondation Ophtalmologique Adolphe de Rothschild, Paris, France.

Design:

Prospective interventional case series.

Methods:

Prospective interventional study of consecutive high hyperopes (≥+3 diopters [D] of spherical equivalent [SE]) undergoing LASIK with the WaveLight FS200 femtosecond and EX500 excimer laser platform. An aspheric ablation profile (planned change in corneal asphericity ΔQ = +0.2) was delivered using the Custom-Q nomogram on an optical zone of ≥6.5 mm centered near the corneal vertex. Uncorrected corrected distance visual acuity (UDVA) and corrected distance visual acuity, as well as changes in SE, corneal asphericity (ΔQ), and higher-order aberrations, were analyzed preoperatively and on day 1, 1, 3, 6, and 12 months.

Results:

117 eyes of 63 patients (mean age of 30.1 ± 5.6 years) were included. Preoperatively and at 12 months postoperatively, the mean SE was 5.1 ± 1.1 D and 0.00 ± 0.7 D, respectively. 88% of eyes achieved 0 logMAR or better UDVA at 12 months. 1 month postoperatively, there was a statistically significant induction of positive spherical aberration decreasing progressively and significantly until the last visit (preop SA4 = 0.09 ± 0.11 μm, day 1 SA4 = 0.30 ± 0.32 μm, 12 months SA4 = 0.08 ± 0.21 μm,P= .056). 2 eyes needed enhancement at 12 months.

Conclusions:

LASIK for high levels of hyperopia showed good outcomes mainly due to aspheric-customized ablation profile with a change of ΔQ = +0.2 in corneal asphericity.
Current state and future perspectives in the diagnosis of eyelid margin disease: clinical review
Authors: Yeu Elizabeth , Garg Sumit , Ayres Brandon D. , Beckman Kenneth , Chamberlain Winston , Lee Barry , Raju Leela , Rao Naveen , Rocha Karolinne Maia , Schallhorn Julie , Zavodni Zachary , Mah Francis S. , Farid Marjan ,   from the ASCRS Cornea Clinical Committee
Published: May 2024

The eyelid margin is vital to ocular surface integrity. Much peer-reviewed literature has been established in eyelid margin inflammation, better known as blepharitis. The purpose was to review and understand the impact of eyelid margin disease. Anterior blepharitis causes inflammation at the eyelash base, ciliary follicles, and the palpebral skin. Posterior blepharitis occurs when there is inflammation with the posterior eyelid margin disease. In common usage, the term “blepharitis” used alone almost always refers to anterior blepharitis. Classification of eyelid margin disease should be based on etiopathogenesis, location, primary vs secondary, and chronicity. Blepharitis has several etiopathologies (infectious, inflammatory, and squamous). Meibomian gland dysfunction (MGD) can refer to the functional and/or structural problems with the meibomian gland. Meibomitis (or meibomianitis) occurs when there is inflammation associated with the MGD. The presence of blepharitis and/or MGD (with or without inflammation) can affect the ocular surface and thereby affect anterior segment and cataract surgeries. This review article evaluates the differential diagnoses of eyelid margin disease, including various forms of blepharitis, MGD, and meibomitis.
Sibling adjustment to diabetes and educational needs
Authors: Jakubowski Tami L. , Curtis Sarah F. , Saylor Jennifer
Published: May 2024

As cases of type 1 diabetes mellitus (T1DM) increase, so do their impact on sibling relationships. This literature review of four databases from 2010 to 2024 discusses findings from five studies and the themes that emerged: education needs and family functioning. Improvements in family-centered care and education are needed for siblings of children with T1DM.
Concomitant Pancreatitis and Pancreatic Neuroendocrine Tumor on MRI and 68Ga-DOTATATE PET/CT
Authors: Wang Jiaqiong , Kuker Russ
Published: May 2024

A 66-year-old woman had an episode of pancreatitis with symptoms starting in October 2023. MRI showed an enhancing soft tissue mass along the superior border of the pancreatic body, as well as signal changes in the pancreatic body and the tail consistent with pancreatitis. The 68Ga-DOTATATE PET/CT demonstrated intense radiotracer uptake within the peripancreatic soft tissue mass, significantly greater than the spleen background. Biopsy of this peripancreatic mass revealed well-differentiated grade 1 neuroendocrine tumor. The body and tail of the pancreas showed diffusely increased 68Ga-DOTATATE uptake but obviously lower than the peripancreatic neuroendocrine tumor, consistent with pancreatitis.
Postsurgical Analgesic Effectiveness of Ultrasound-Guided Parasternal Block After Auricular Reconstruction Using Autologous Costal Cartilage in Pediatric Patients: A Randomized Controlled Trial
Authors: Chen Keyu , Xiang Guihua , Chen Chunmei , Liu Quanle , Jin Jing , Huang Lan , Yang Dong
Published: May 2024

Objective:

To study the efficacy of ultrasound-guided parasternal block (US-PSI) in pediatric patients undergoing auricular reconstruction surgery.

Methods:

For this study, the authors recruited 60 children between the ages of 5 and 12 years who underwent auricular reconstruction with autologous costal cartilage (ACC) to correct microtia. They were randomized to receive either ultrasound-guided modified parasternal block or periprostatic local infiltration anesthesia (PLIA), with 30 cases in each group. Ultrasound-guided parasternal block was administered following anesthesia induction, whereas PLIA was administered after ACC harvest. Lastly, following surgery, all children were provided with patient-controlled intravenous analgesia with sufentanil, and the numeric pain rating scale (NRS) was used to assess the intensity of pain. Our primary outcomes were the resting NRS pain scores and the NRS scores upon coughing at 1, 6, 12, 24, and 48 hours postsurgery. Sufentanil consumption within the first 24 hours of surgery, the mean duration to first ambulation, and the usage of rescue analgesics were our secondary outcomes. The authors also recorded the occurrence of undesirable side effects as well as more serious side effects like pneumothorax.

Results:

Pediatric patients who were administered US-PSI showed significantly reduced NRS chest pain scores at 6 and 12 hours postsurgery compared to those who received PLIA (P<0.05). In addition, sufentanil consumption within the first 24 hours postsurgery, duration to first ambulation, and use of rescue analgesics were significantly lower among patients in the US-PSI group when compared to those in the PLIA group (P<0.05).

Conclusions:

This study found that US-PSI was a highly efficacious and safe technique for postsurgical analgesia following auricular reconstruction with ACC in pediatric patients.

Level of Evidence:

Level II, therapeutic study.
A Bibliometric Analysis of Publications on Cadavers: A Study Based on Web of Science Data From 1978 to 2023
Authors: Polat Sema , Tunç Mahmut , Özşahin Esin , Göker Pinar
Published: May 2024

This study aimed to investigate the significance of publications examining the effectiveness of cadaver studies in the field of medicine with the method of bibliometric analysis, which emerged in the 1950s, offers the opportunity to conduct a detailed analysis of a specific subject, just like a systematic literature review or meta-analysis. Also, it aimed to enlighten the content of cadaver studies in the last half-century and to present a perspective for the future. In the study, an advanced search was conducted on the Web of Science Core Collection database on August 1, 2023, using the keywords “cadaver,” “cadaver study,” “cadaveric dissection.” Review articles were excluded from the study. There were determined 34554 documents. The documents were transferred to the VOSviewer software program. In this way, the authors made detailed analyses of authors, keywords, journals, organizations, institutions, and countries and created scientific maps. The United States was one of the most important countries in terms of research. Generally, the use of cadaver terms in documents belongs to surgery, anatomy, and transplantation journals. Anatomy, cadaver, biomechanics, ultrasound, and computed tomography were the top 5 most frequently used keywords with cadaver term. The findings of our study showed that cadaver studies are used in many fields of medical science. However, clinical studies, including advanced imaging techniques, draw attention to the developing technology. Along with the powerful institutions of the United States, its great contributions to publications stand out.
Reducing Chronic Opioid Use
Authors: Jogerst Kristen , Gupta Nikita , Kosiorek Heidi E. , Lee Yeonsoo S. , Abujbarah Sami , Cronin Patricia , Casey William , Pockaj Barbara
Published: May 2024

Objective:

This study investigates Enhanced Recovery After Surgery (ERAS®) protocols’ impact on long-term opioid and sedative use following mastectomy with or without implant-based breast reconstruction (IBBR).

Summary Background Data:

ERAS® protocols for patients undergoing mastectomy with or without IBBR are associated with decreased length of stay, increased rate of same-day discharge, decreased postoperative pain, and decreased postoperative opioid requirements. However, less is known about their effect on opioid and sedative use beyond 90 days after surgery.

Methods:

A retrospective review of all patients undergoing mastectomy with or without IBBR at a single institution between January 2013 and December 2019. Mastectomy ERAS® protocols were implemented in February 2017, creating two groups: pre-ERAS® and ERAS®. Baseline characteristics and prevalence of chronic opioid and sedative use were compared. Univariable and multivariable logistic regression predicted factors associated with increased odds of chronic opioid and sedative use.

Results:

756 patients were evaluated: 405 pre-ERAS® and 351 ERAS®. Post-ERAS®, chronic opioid use decreased in opioid-naïve (40% vs. 30%, P=0.024) and opioid-tolerant patients (58% vs. 37%, P=0.002), with no increase in chronic sedative use. There were decreased odds of chronic opioid use for all ERAS® patients (OR=0.57, 95% CI: 0.42-0.76)), and of IBBR patients, those receiving subcutaneous implants (OR=0.31, 95% CI: 0.20-0.48). There was increased chronic opioid-use odds if undergoing bilateral surgery (OR=1.54, 95% CI: 1.14-2.08), two-stage reconstruction (OR=9.78, 95% CI: 5.94-16.09), and for patients with higher PACU pain scores (OR=1.09, 95% CI: 1.03-1.14) or >150 discharge OMEs (OR=2.63, 95% CI: 1.48-4.68).

Conclusion:

ERAS® protocols for mastectomy patients with or without IBR are associated with decreases in chronic opioid use, without concomitant increases in chronic sedative use.
EZ-SPOTs: A simple and robust high-throughput liquid handling platform
Authors: Albo Jon , Tan Shenghao , Denis Joee D , Franklin-Guild Rebecca , Shiri Samira , Sandoz Kelsi M , Cira Nate J
Published: May 2024

Liquid handling is a fundamental capability for many scientific experiments. Previously, we introduced the Surface Patterned Omniphobic Tiles (SPOTs) platform, which enables manipulation of hundreds to thousands of independent experiments without costly equipment or excessive consumable expenses. However, the SPOTs platform requires a custom coating formulation and lacks robustness. To overcome these limitations, we introduce EZ-SPOTs. These devices can be created in an hour with common fabrication tools and just three components - glass, a hydrophobic coating, and acrylic. EZ-SPOTs preserve many of the SPOTs platform’s strengths - ease of use, ability to handle a wide range of volumes, and scalability - and adopt a durable and abrasion resistant coating that enables multiple reuses of each device. Here, we describe the fabrication of EZ-SPOTs and showcase how its reusability allows antibiotic susceptibility testing of many isolates using a single device. These results quantitatively match current gold standard assays and the increased throughput provides substantially more information than standard approaches.
Mapping Endothelial-Macrophage Interactions in Diabetic Vasculature: Role of TREM2 in Vascular Inflammation and Ischemic Response
Authors: Malhi Naseeb Kaur , Luo Yingjun , Tang Xiaofang , Chadha Rahuljeet Singh , Tapia Alonso , Liu Xuejing , Chen Muxi , Yuan Dongqiang , Qi Meirigeng , Wei Lu , Cooke John P. , Natarajan Rama , Southerland Kevin W. , Chen Zhen Bouman
Published: May 2024

Vasculopathies occur 15 years earlier in individuals with diabetes mellitus (DM) as compared to those without, but the underlying mechanisms driving diabetic vasculopathy remain incompletely understood. Endothelial cells (ECs) and macrophages (MΦ) are critical players in vascular wall and their crosstalk is crucial in diabetic vasculopathy. In diabetes, EC activation enables monocyte recruitment, which transmigrate into the intima and differentiate into macrophages (MΦ). Beyond this established model of diapedesis, EC-MΦ interplay is highly intricate and heterogenous. To capture these highly context dependent EC-MΦ interactions, we leveraged single-cell (sc)RNA-seq in conjunction with spatial transcriptome (ST)-seq profiling to analyze human mesenteric arteries from non-diabetic (ND) and type 2 diabetic (T2D) donors. We provide in this study a transcriptomic map encompassing major arterial vascular cells, e.g., EC, mononuclear phagocyte (MP), and T cells, and their interactions associated with human T2D. Furthermore, we identified Triggering Receptor Expressed on Myeloid Cells 2 (TREM2)as a top T2D-induced gene in MP, with concomitant increase of TREM2 ligands in ECs. TREM2 induction was confirmed in mouse models of T2D and monocyte/MΦ subjected to DM-mimicking stimuli. Perturbing TREM2 with either an antibody or silencing RNA in MPs led to decreased pro-inflammatory responses in MPs and ECs and increased EC migrationin vitro. In a mouse model of diabetes, TREM2 expression and its interaction with ECs are increased in the ischemic, as compared to non-ischemic muscles. Importantly, neutralization of TREM2 using a neutralizing antibody enhanced ischemic recovery and flow reperfusion in the diabetic mice, suggesting a role of TREM2 in promoting diabetic PAD. Finally, we verified that both TREM2 expression and the TREM2-EC-interaction are increased in human patients with DM-PAD. Collectively, our study presents the first atlas of human diabetic vessels with a focus on EC-MP interactions. Exemplified by TREM2, our study provides valuable insights into EC-MΦ interactions, key processes contributing to diabetic vasculopathies and the potential of targeting these interactions for therapeutic development.
Do nutritional interventions before or during pregnancy affect placental phenotype? Findings from a systematic review of human clinical trials
Authors: Bonnell V , White M , Connor KL
Published: May 2024

Background

Maternal nutritional interventions aim to address nutrient deficiencies in pregnancy, a leading cause of maternal and neonatal morbidity and mortality worldwide. How these interventions influence the placenta, which plays a vital role in fetal growth and nutrient supply, is not well understood. This is a major gap in understanding how such interventions could influence pregnancy outcomes and fetal health. We hypothesised that nutritional interventions influence placental phenotype, and that these placental changes relate to how successful, or not, the intervention is in improving pregnancy outcomes.

Methods

We conducted a systematic review and followed PRISMA-2020 reporting guidelines. Articles were retrieved from PubMed, Clinicaltrials.gov, and ICTRP-WHO using pre-defined search terms and screened by two reviewers using a 3-level process. Inclusion criteria considered articles published from January 2001-September 2021 that reported on clinical trials in humans, which administered a maternal nutritional intervention during the periconceptional or pregnancy period and reported on placental phenotype (shape and form, function or placental disorders).

Findings

Fifty-three eligible articles reported on (multiple) micronutrient- (n=33 studies), lipid- (n=11), protein- (n=2), and diet-/lifestyle-based (n=8) interventions. Of the micronutrient-based interventions, 16 (48%) associated with altered placental function, namely altered nutrient transport/metabolism (n=9). Nine (82%) of the lipid-based interventions associated with altered placental phenotype, including elevated placental fatty acid levels (n=5), altered nutrient transport/metabolism gene expression (n=4), and decreased inflammatory biomarkers (n=2). Of the protein-based interventions, two (66%) associated with altered placental phenotype, including increased placental efficiency (n=1) or decreased preeclampsia risk (n=1). Three (38%) of diet and lifestyle-based interventions associated with placental changes, namely placental gene expression (n=1) and disease (n=2). In studies with data on maternal (n=30) or offspring (n=20) outcomes, interventions that influenced placental phenotype were more likely to have also associated with improved maternal outcomes (11/15 [73%]) and offspring birth outcomes (6/11 [54%]), compared to interventions that did not associate with placental changes (2/15 [13%] and 1/9 [11%], respectively).

Conclusions

Periconceptional and prenatal nutritional interventions to improve maternal/pregnancy health associate with altered placental development and function. These placental adaptations likely benefit the pregnancy and improve offspring outcomes. Understanding the placenta’s role in the success of interventions to combat nutrient deficiencies is critical for improving interventions and reducing maternal and neonatal morbidity and mortality globally.
GeoAB: Towards Realistic Antibody Design and Reliable Affinity Maturation
Authors: Lin Haitao , Wu Lirong , Huang Yufei , Liu Yunfan , Zhang Odin , Zhou Yuanqing , Sun Rui , Li Stan Z.
Published: May 2024

Increasing works for antibody design are emerging to generate sequences and structures in Complementarity Determining Regions (CDRs), but problems still exist. We focus on two of them:(i) authenticity of the generated structureand(ii) rationality of the affinity maturation, and propose GEOAB as a solution. In specific, GeoABDesigner generates CDR structures with realistic internal geometries, composed of a generative geometry initializer (Geo-Initializer) and a position refiner (Geo-Refiner); GeoAB-Optimizer achieves affinity maturation by accurately predicting both the mutation effects and structures of mutant antibodies with the same network architecture as Geo-Refiner. Experiments show that GEOAB achieves state-of-the-art performance in CDR co-design and mutation effect predictions, and fulfills the discussed tasks effectively.
Predicting “pain genes”: multi-modal data integration using probabilistic classifiers and interaction networks
Authors: Zhao Na , Bennett David L , Baskozos Georgios , Barry Allison M
Published: May 2024

Accurate identification of pain-related genes remains challenging due to the complex nature of pain pathophysiology and the subjective nature of pain reporting in humans, or inferring pain states in animals on the basis of behaviour. Here, we use a machine learning approach to identify possible “pain genes”. Labelling was based on a gold-standard list of genes with validated involvement across pain conditions, and was trained on a selection of -omics (eg. transcriptomics, proteomics, etc.), protein-protein interaction (PPI) network features, and biological function readouts for each gene. Multiple classifiers were trained, and the top-performing model was selected to predict a “pain score” per gene. The top ranked genes were then validated against pain-related human SNPs to validate against human genetics studies. Functional analysis revealed JAK2/STAT3 signal, ErbB, and Rap1 signalling pathways as promising targets for further exploration, while network topological features contribute significantly to the identification of “pain” genes. As such, a PPI network based on top-ranked genes was constructed to reveal previously uncharacterised pain-related genes including CHRFAM7A and UNC79. These analyses can be further explored using the linked open-source database athttps://livedataoxford.shinyapps.io/drg-directory/, which is accompanied by a freely accessible code template and user guide for wider adoption across disciplines. Together, the novel insights into pain pathogenesis can indicate promising directions for future experimental research.