bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of smoking status on clinical outcomes in patients with metastatic renal cell carcinoma treated with first-line immune checkpoint inhibitor-based regimens
Authors: Saad Eddy , Gebrael Georges , Semaan Karl , Eid Marc , Saliby Renée Maria , Labaki Chris , Sayegh Nicolas , Wells J Connor , Takemura Kosuke , Ernst Matthew Scott , Lemelin Audreylie , Basappa Naveen S , Wood Lori A , Powles Thomas , Ernst D Scott , Lalani Aly-Khan A , Agarwal Neeraj , Xie Wanling , Heng Daniel Y C , Choueiri Toni K
Published: April 2024

Background

Current tobacco smoking is independently associated with decreased overall survival (OS) among patients with metastatic renal cell carcinoma (mRCC) treated with targeted monotherapy (VEGF-TKI). Herein, we assess the influence of smoking status on the outcomes of patients with mRCC treated with the current first-line standard of care of immune checkpoint inhibitor (ICI)-based regimens.

Materials and Methods

Real-world data from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) were collected retrospectively. Patients with mRCC who received either dual ICI therapy or ICI with VEGF-TKI in the first-line setting were included and were categorized as current, former, or nonsmokers. The primary outcomes were OS, time to treatment failure (TTF), and objective response rate (ORR). OS and TTF were compared between groups using the log-rank test and multivariable Cox regression models. ORR was assessed between the 3 groups using a multivariable logistic regression model.

Results

A total of 989 eligible patients were included in the analysis, with 438 (44.3%) nonsmokers, 415 (42%) former, and 136 (13.7%) current smokers. Former smokers were older and included more males, while other baseline characteristics were comparable between groups. Median follow-up for OS was 21.2 months. In the univariate analysis, a significant difference between groups was observed for OS (P = .027) but not for TTF (P = .9), with current smokers having the worse 2-year OS rate (62.8% vs 70.8% and 73.1% in never and former smokers, respectively). After adjusting for potential confounders, no significant differences in OS or TTF were observed among the 3 groups. However, former smokers demonstrated a higher ORR compared to never smokers (OR 1.45, P = .02).

Conclusion

Smoking status does not appear to independently influence the clinical outcomes to first-line ICI-based regimens in patients with mRCC. Nonetheless, patient counseling on tobacco cessation remains a crucial aspect of managing patients with mRCC, as it significantly reduces all-cause mortality.
Three-dimensional reconstruction and multiomics analysis reveal a unique pattern of embryogenesis in Ginkgo biloba
Authors: Ma Lingyu , Hu Zijian , Shen Weiwei , Zhang Yingying , Wang Guangchao , Chang Bang , Lu Jinkai , Cui Yaning , Xu Huimin , Feng Yun , Jin Biao , Zhang Xi , Wang Li , Lin Jinxing
Published: April 2024

Ginkgo (Ginkgo biloba L.) is one of the earliest extant species in seed plant phylogeny. Embryo development patterns can provide fundamental evidence for the origin, evolution, and adaptation of seeds. However, the architectural and morphological dynamics during embryogenesis in G. biloba remain elusive. Herein, we obtained over 2,200 visual slices from 3 stages of embryo development using micro-computed tomography imaging with improved staining methods. Based on 3-dimensional (3D) spatiotemporal pattern analysis, we found that a shoot apical meristem with 7 highly differentiated leaf primordia, including apical and axillary leaf buds, is present in mature Ginkgo embryos. 3D rendering from the front, top, and side views showed 2 separate transport systems of tracheids located in the hypocotyl and cotyledon, representing a unique pattern of embryogenesis. Furthermore, the morphological dynamic analysis of secretory cavities indicated their strong association with cotyledons during development. In addition, we identified genes GbLBD25a (lateral organ boundaries domain 25a), GbCESA2a (cellulose synthase 2a), GbMYB74c (myeloblastosis 74c), GbPIN2 (PIN-FORMED 2) associated with vascular development regulation, and GbWRKY1 (WRKYGOK 1), GbbHLH12a (basic helix–loop–helix 12a), and GbJAZ4 (jasmonate zim-domain 4) potentially involved in the formation of secretory cavities. Moreover, we found that flavonoid accumulation in mature embryos could enhance postgerminative growth and seedling establishment in harsh environments. Our 3D spatial reconstruction technique combined with multiomics analysis opens avenues for investigating developmental architecture and molecular mechanisms during embryogenesis and lays the foundation for evolutionary studies of embryo development and maturation.
Inhibition effect of copper-bearing metals on arterial neointimal hyperplasia via the AKT/Nrf2/ARE pathway in vitro and in vivo
Authors: Wang Peng , Xu Xiaohe , Gu Guisong , Guo Qianwen , Rao Yanzhi , Yang Ke , Xi Tong , Yuan Yonghui , Chen Shanshan , Qi Xun
Published: April 2024

In-stent restenosis can be caused by the activation, proliferation and migration of vascular smooth muscle cells (VSMCs), which affects long-term efficacy of interventional therapy. Copper (Cu) has been proved to accelerate the endothelialization and reduce thrombosis formation, but little is known about its inhibition effect on the excessive proliferation of VSMCs. In this study, 316L-Cu stainless steel and L605-Cu cobalt-based alloy with varying Cu content were fabricated and their effects on surface property, blood compatibility and VSMCs were studied in vitro and in vivo. CCK-8 assay and EdU assay indicated that the Cu-bearing metals had obvious inhibitory effect on proliferation of VSMCs. Blood clotting and hemolysis tests showed that the Cu-bearing metals had good blood compatibility. The inhibition effect of the Cu-bearing metals on migration of cells was detected by Transwell assay. Further studies showed that Cu-bearing metals significantly decreased the mRNA expressions of bFGF, PDGF-B, HGF, Nrf2, GCLC, GCLM, NQO1 and HO1. The phosphorylation of AKT and Nrf2 protein expressions in VSMCs were significantly decreased by Cu-bearing metals. Furthermore, it was also found that SC79 and TBHQ treatments could recover the protein expressions of phospho-AKT and Nrf2, and their downstream proteins as well. Moreover, 316L-Cu stent proved its inhibitory action on the proliferation of VSMCs in vivo. In sum, the results demonstrated that the Cu-bearing metals possessed apparent inhibitory effect on proliferation and migration of VSMCs via regulating the AKT/Nrf2/ARE pathway, showing the Cu-bearing metals as promising stent materials for long-term efficacy of implantation.
Risk of Post-Intubation Laryngotracheal Stenosis With Respect to COVID-19 Status in a Large Multicenter Cohort Cross-Sectional Study
Authors: Gray Raluca , Pradhan Prajwal Mani , Hoffmeister Jesse , Misono Stephanie , Cho Roy , Tignanelli Christopher
Published: April 2024

OBJECTIVES:

Occurrence of post-intubation laryngotracheal stenosis (LTS) with respect to COVID-19 status.

DESIGN:

Retrospective cross-sectional inpatient database.

SETTING:

Eleven Midwest academic and community hospitals, United States.

PATIENTS:

Adults, mechanically ventilated, from January 2020 to August 2022, who were subsequently readmitted within 6 months with a new diagnosis of LTS.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Six thousand eight hundred fifty-one COVID-19 negative and 1316 COVID-19 positive patients were intubated and had similar distribution by age (median 63.77 vs. 63.16 yr old), sex (male, 60.8%; n = 4173 vs. 60%; n = 789), endotracheal tube size (≥ 7.5, 75.8%; n = 5192 vs. 75.5%; n = 994), and comorbidities. The ICU length of stay (median [interquartile range (IQR)], 7.23 d [2.13–16.67 d] vs. 3.95 d [1.91–8.88 d]) and mechanical ventilation days (median [IQR], 5.57 d [1.01–14.18 d] vs. 1.37 d [0.35–4.72 d]) were longer in the COVID-19 positive group. The occurrence of LTS was double in the COVID-19 positive group (12.7%, n = 168 vs. 6.4%, n = 440; p < 0.001) and was most commonly diagnosed within 60 days of intubation. In multivariate analysis, the risk of LTS increased by 2% with each additional ICU day (hazard ratio [HR], 1.02; 95% CI, 1.02–1.03; p < 0.001), by 3% with each additional day of ventilation (HR, 1.03; 95% CI, 1.02–1.04; p < 0.001), and by 52% for each additional reintubation (HR, 1.52; 95% CI, 1.36–1.71; p < 0.001). We observed no significant association COVID-19 status and risk of LTS.

CONCLUSIONS:

The occurrence of post-intubation LTS was double in a COVID-19 positive cohort, with higher risk with increasing number of days intubated, days in the ICU and especially with the number of reintubations. COVID-19 status was not an independent risk factor for LTS.
Pinch Grafting: A Systematic Review of Modern Perspectives and Applications in Dermatologic Surgery and Wound Healing
Authors: Jeha George M. , Hill Emma , Taylor Laura , Davis Michael , Greenway Hubert T. , Kelley Benjamin
Published: April 2024

BACKGROUND

Pinch grafting has experienced a resurgence in interest in recent years, stemming from its simplicity, safety, and potential in restoring tissue integrity. While historically employed for chronic nonhealing wounds, pinch grafts have shown promise following surgical procedures, particularly those involving the lower extremities.

OBJECTIVE

To systematically review the literature and present an updated overview of the current applications of pinch grafting.

METHODS

A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. In collaboration with a medical reference librarian, the PubMed, Embase, Scopus, and Web of Science databases were searched for studies reporting on the use of pinch grafting from 2000 onward. The references of each included article were also screened.

RESULTS

Ten articles met final inclusion criteria. In total, 300 patients underwent pinch grafting for treatment of skin ulceration, while an additional 35 cases were performed as an alternative to primary closure following skin cancer resection. Overall, pinch grafting was safe and well tolerated, with minimal adverse outcomes reported.

CONCLUSION

Pinch grafting is a safe, straightforward, and effective technique to promote the healing of chronic wounds. While the procedure shows early promise in emerging applications within dermatologic surgery, only about 10% of the reported cases involved this indication, reflecting a need for further research in this area.
Comparing PCSK9 Monoclonal Antibody Treatment Strategies Following Myocardial Infarction Using Negative Control Outcomes: A Target Trial Emulation Study
Authors: Sloot Rosa , Breskin Alexander , Colantonio Lisandro D. , Allmon Andrew G. , Yu Ying , Sakhuja Swati , Chen Ligong , Muntner Paul , Brookhart M. Alan , Dhalwani Nafeesa
Published: April 2024

Background:

Initiation of proprotein convertase subtilisin/kexin type 9 monoclonal antibody (PCSK9 mAb) for lipid-lowering following myocardial infarction (MI) is likely affected by patients’ prognostic factors, potentially leading to bias when comparing real-world treatment effects.

Methods:

Using target-trial emulation, we assessed potential confounding when comparing two treatment strategies post-MI: initiation of PCSK9 mAb within 1 year and no initiation of PCSK9 mAb. We identified MI hospitalizations during July 2015–June 2020 for patients aged ≥18 years in Optum’s de-identified Clinformatics Data Mart (CDM) and MarketScan, and those aged ≥66 in the US Medicare claims database. We estimated a 3-year counterfactual cumulative risk and risk difference (RD) for 10 negative control outcomes using the clone–censor–weight approach to address time-varying confounding and immortal person-time.

Results:

PCSK9 mAb initiation within 1-year post-MI was low (0.7% in MarketScan and 0.4% in both CDM and Medicare databases). In CDM, there was a lower risk for cancer (RD = −3.6% [95% CI: −4.3%, −2.9%]), decubitus ulcer (RD = −7.7% [95% CI: −11.8%, −3.7%]), fracture (RD = −8.1% [95% CI: −9.6%, −6.6%]), influenza vaccine (RD = −9.3% [95% CI: −17.5%, −1.1%]), and visual test (RD = −0.6% [95% CI: −0.7%, −0.6%]) under the PCSK9 mAb initiation versus no initiation strategy. Similar differences persisted in the MarketScan and Medicare databases. In each database, ezetimibe and low-density lipoprotein testing were unbalanced between treatment strategies.

Conclusion:

A comparative effectiveness study of these treatments using the current approach would likely bias results due to the low number of PCSK9 mAb initiators.
Errors in the Calculation of the Population Attributable Fraction
Authors: Suzuki Etsuji , Yamamoto Eiji
Published: April 2024

One of the common errors in the calculation of the population attributable fraction (PAF) is the use of an adjusted risk ratio in the Levin formula. In this article, we discuss the errors visually using wireframes by varying the standardized mortality ratio (SMR) and associational risk ratio (aRR) when the prevalence of exposure is fixed. When SMR >1 and SMR > aRR, the absolute bias is positive, and its magnitude increases as the difference between SMR and aRR increases. By contrast, when aRR > SMR > 1, the absolute bias is negative and its magnitude is relatively small. Moreover, when SMR > aRR, the relative bias is larger than one, whereas when SMR < aRR, the relative bias is smaller than one. Although the target population of the PAF is the total population, the target of causation of the PAF is not the total population but the exposed group.
Defining the Safe Entry Point in Deep Plane Facelifting with Novel Landmark for the Buccal Branch of the Facial Nerve
Authors: Medhurst Ryan , Tremblay Cory , Marrelli Kristina , Best Corliss , Jadeski Lorraine , Brace Matthew
Published: April 2024

Background:

In deep facial surgery, accurate preoperative landmarking of branches of the facial nerve is helpful in avoiding inadvertent facial nerve injury. The objective of our study was to determine the accuracy at which the intersection point of two bisecting lines that join facial surface landmarks can be used to accurately locate the buccal branch(es) of the facial nerve, specifically at the deep plane entry point (ie, intercept landmark).

Methods:

Thirty-three cadavers were dissected to determine the position of the buccal rami relative to the intercept.

Results:

Buccal rami crossed the intercept in 12.12% of specimens (0 mm from intercept, n = 4). Buccal rami passed superiorly in 66.67% of specimens (3.71 ± 3.28 mm from intercept, n = 7) and inferiorly in 21.21% of specimens (2.44 ± 0.92 mm from intercept, n = 7). Noteworthy, buccal rami were located within 1 cm of the intercept landmark with 96.97% accuracy (32/33 cadavers).

Conclusions:

These data suggest that this novel intercept (1) reliably locates the buccal branch of the facial nerve as it courses distal to the parotid gland, and (2) helps define a “safe zone” for entry into the deep plane where the likelihood of encountering the facial nerve is extremely low.
Optimizing Aesthetic Outcomes in Autologous Breast Reconstruction: 20 Pearls for Practice
Authors: Sinik Lauren M. , Le Audrey , Ehirim Henrietta , Collins Meredith S.
Published: April 2024

Autologous breast reconstruction with a deep inferior epigastric artery perforator (DIEP) flap is an excellent option for many patients proceeding with mastectomy for surgical management of their breast cancer. As microsurgical techniques and results improve and ensure consistent flap survival, optimizing aesthetic outcomes may become a primary focus. This article outlines 20 tips that can improve aesthetic results in DIEP flap breast reconstruction, based on our senior author’s 8-year career in microsurgical breast reconstruction, with an emphasis on enhanced cosmesis. We highlight tips on preoperative planning, intraoperative, and revision stages of the reconstruction and provide a schematic for integrating the tips into a reader’s microsurgical breast reconstruction practice.
The Epidemiology, Management, and Outcomes of Civilian Gunshot Wounds to the Upper Extremity at an Urban Trauma Center
Authors: Muss Tessa E. , Hu Sophia , Bauder Andrew R. , Lin Ines C.
Published: April 2024

Background:

Gunshot wounds (GSWs) create significant morbidity in the United States. Upper extremity (UE) GSWs are at high risk of combined injuries involving multiple organ systems and may require variable treatment strategies. This study details the epidemiology, management, and outcomes of civilian UE GSWs at an urban level 1 trauma center.

Methods:

Using the University of Pennsylvania Trauma Registry, all adult patients with UE GSWs from 2015 to 2020 who were at least 6-months postinjury were studied for demographics, injury pattern, operative details, and postoperative outcomes. Fisher exact and Wilcoxon rank sum tests were used to determine differences in treatment modalities and outcomes.

Results:

In 360 patients, the most common victim was young (x̄ = 29.5 y old), African American (89.4%), male (94.2%), and had multiple GSWs (70.3%). Soft tissue-only trauma (47.8%) and fractures (44.7%) predominated. Presence of fracture was independently predictive of neurologic, vascular, and tendinous injuries (P < 0.001). Most soft tissue-only injuries were managed nonoperatively (162/173), whereas fractures frequently required operative intervention (115 of 161, P < 0.001). Despite a prevalence of comminuted (84.6%) and open (43.6%) fractures, hardware complications (7.5%) and wound infection (1.1%) occurred infrequently.

Conclusions:

Civilian GSWs to the UE with only soft tissue involvement can often be managed conservatively with antibiotic administration, bedside washout, and local wound care. Even with combined injuries and open fractures, single-stage operative debridement and fracture care with primary or secondary closure often prevail. As civilian ballistic trauma becomes more frequent in the United States, these data help inform patient expectations and guide management.
A Novel Technique for scleral fixation of Carlevale Intraocular Lens without conjunctival opening utilizing Hoffman Pockets
Authors: Manousakis Evangelos , Gartaganis Panos S. , Manousakis Emmanouil , Karmiris Efthymios
Published: April 2024

Purpose:

To report a novel surgical technique for scleral fixation of Carlevale intraocular lens (IOL) without conjunctival dissection using Hoffman pockets.

Methods:

An 80-years-old female with IOL dislocation in her right eye required IOL exchange. After removing the dislocated IOL, a Carlevale IOL was implanted, securing the self-blocking harpoons within scleral pockets which were constructed using Hoffman technique.

Results:

Surgical procedure was uneventful. During the next 3 months follow up, Carlevale IOL remained stable within the scleral pockets, and no signs of IOL dislocation or decentration were observed. Visual acuity significantly improved from 20/200 preoperatively up to 20/32 postoperatively due to corneal scaring from previous herpetic keratitis. No postoperative complications were recorded.

Conclusion:

Creating scleral pockets without conjunctival dissection using Hoffman pockets technique, represent a reliable and effective method for achieving both secure fixation and effective scleral covering of Carlevale IOL haptics. Absence of conjunctival opening, apart from patient postoperative comfort, reduces risk of postoperative complications, including conjunctival erosion and infection. The presented technique offers a promising alternative for Carlevale IOL scleral fixation.
Venovenous extracorporeal membrane oxygenation for severe acute respiratory distress syndrome in metastatic choriocarcinoma during systemic chemotherapy: Case report
Authors: Cappelli Jared , Edwards Amber , Emling Jonathan
Published: April 2024

Rationale:

Gestational trophoblastic neoplasms are rare and include multiple different types of tumors such as hydatidiform moles, placental site trophoblastic tumors, and choriocarcinoma. Metastatic choriocarcinoma is well described with an excellent prognosis when treated appropriately with chemotherapy. The most common location for metastatic disease is the lungs which can unfortunately lead to severe acute respiratory distress syndrome (ARDS) in the most severe cases.

Patient concerns:

Metastatic cancer has historically been a contraindication for the use of extracorporeal life support (including extracorporeal membrane oxygenation or extracorporeal membrane oxygenation [ECMO]). With advancing technology and medicine, this contraindication has been called into question. Prior case reports describe the use of ECMO in complicated cases of metastatic cancer and even choriocarcinoma with lung metastasis and refractory ARDS.

Diagnoses:

We describe a case in which a patient with choriocarcinoma in viable pregnancy developed lung metastasis and ARDS.

Interventions:

The patient was managed with venovenous ECMO successfully.

Outcomes:

The patient was cannulated for VV-ECMO for 14 days with subsequent full pulmonary recovery.

Lessons:

The purpose of this work is to help providers understand the broad utility of ECMO and the need to assess candidacy for this therapy on a case by case basis, even in the setting of metastatic cancer.
Preclinical models for bladder cancer therapy research
Authors: Ertl Iris , Shariat Shahrokh F. , Berger Walter , Englinger Bernard
Published: April 2024

Purpose of review

Bladder cancer (BC) is a highly heterogenous disease comprising tumours of various molecular subtypes and histologic variants. This heterogeneity represents a major challenge for the development of novel therapeutics. Preclinical models that closely mimic in vivo tumours and reflect their diverse biology are indispensable for the identification of therapies with specific activity in various BC subtypes. In this review, we summarize efforts and progress made in this context during the last 24 months.

Recent findings

In recent years, one main focus was laid on the development of patient-derived BC models. Patient-derived organoids (PDOs) and patient-derived xenografts (PDXs) were demonstrated to widely recapitulate the molecular and histopathological characteristics, as well as the drug response profiles of the corresponding tumours of origin. These models, thus, represent promising tools for drug development and personalized medicine. Besides PDXs, syngenic in vivo models are of growing importance. Since these models are generated using immunocompetent hosts, they can, amongst others, be used to develop novel immunotherapeutics and to evaluate the impact of the immune system on drug response and resistance.

In the past two years, various in vivo and in vitro models closely recapitulating the biology and heterogeneity of human bladder tumours were developed.
The Effect of an Educational Intervention on Nurses' Knowledge, Beliefs, and Actions to be Taken, Regarding Suicide
Authors: Kramer Margaret , Miniard Samantha , Hayden Maria , Hovermale Rachael , Jones Aileen , Davies Claire C. , Monroe Martha , Ponder Judy , Miller Brook
Published: April 2024

OBJECTIVE

The aim of this study was to examine the effect of an educational intervention on nurses' knowledge defined as understanding, beliefs, and actions to be taken, regarding nurse suicide.

BACKGROUND

Between 2007 and 2018, nurses were 18% more likely to die by suicide than the general public. As a result, an assessment of nurses' knowledge regarding suicide has become an important issue for nursing administration.

METHODS

A quasi-experiment (N = 225) was conducted. Variables of interest were assessed pre and post an educational intervention on 3 domains related to suicide.

RESULTS

Significant and meaningful differences were found regarding 2 domains of interest in nurses' understanding related to nurse suicide, and actions to be taken, pre and post intervention. A significant change occurred regarding beliefs; however, the difference was small and therefore not meaningful.

CONCLUSIONS

Finding demonstrate that educational interventions focused on issues related to suicide can enhance nurses' knowledge of the challenges implicit when one considers taking one's own life.
Upper Limb Casting Application Post-Botulinum Toxin Injection for Elbow Spasticity: A Guided Casting Protocol
Authors: WORTLEY Kate , CARDA Stefano , GANZERT Carl , FARAG Jordan , REEBYE Rajiv
Published: April 2024

Casting is an effective adjunctive treatment which increases the effects of botulinum toxin on patients with spasticity. The evidence for casting as an adjunctive therapy post-botulinum toxin has been well documented in the literature. However, standardized casting protocols are lacking, with no published descriptions of upper limb casting application post-botulinum toxin injection for spasticity. In this paper we will describe our experience regarding the application of upper limb casting as an adjunctive therapy for elbow spasticity, detailing indications, contraindications and description of our protocol (materials required and technique).
Effects of Russian and Aussie Currents Combined With Isokinetic Training on Symptoms, Pain, Functional Mobility, and Quality of Life in Individuals With Patellofemoral Pain Syndrome
Authors: Çankaya Musa , Karakaya İlkim Çitak , Yargiç Pelin Melda , Karakaya Mehmet Gürhan
Published: April 2024

Objective

To find out if burst-modulated medium frequency alternating currents (Russian and Aussie types) contribute to the effects of isokinetic-training in patients with patellofemoral pain, and to compare their effectiveness on symptoms, pain, functional mobility, and quality of life.

Design

Forty-five patients with patellofemoral pain were randomized into Russian current, Aussie current or placebo electrical stimulation groups. Patellofemoral Pain Severity Scale, Stair Climbing Test, Anterior Knee Pain Scale, Knee Outcome Survey Activities of Daily Living Scale, and Short Form-36 data were obtained before and after 15 sessions of interventions and at the end of a 3-wk follow-up period.

Results

Severity of symptoms and pain decreased; functional mobility, activity limitations and quality of life improved significantly after interventions (P < 0.05), and these effects were maintained at the follow-up period (P < 0.05). The amount of improvements in symptom and pain severity, and quality of life was higher in the Russian and Aussie current groups than in the placebo group (P < 0.05).

Conclusions

In patients with patellofemoral pain, burst-modulated medium frequency alternating currents may provide extra benefit in improving symptoms, pain, functional mobility and quality of life, and the Aussie currents provide greater improvement in symptom and pain severity.
Glial Activity Load on PET Reveals Persistent “Smoldering” Inflammation in MS Despite Disease-Modifying Treatment
Authors: Singhal Tarun , Cicero Steven , Rissanen Eero , Ficke John , Kukreja Preksha , Vaquerano Steven , Glanz Bonnie , Dubey Shipra , Sticka William , Seaver Kyle , Kijewski Marie , Callen Alexis M. , Chu Renxin , Carter Kelsey , Silbersweig David , Chitnis Tanuja , Bakshi Rohit , Weiner Howard L.
Published: April 2024

Purpose of the Report

18F-PBR06-PET targeting 18-kDa translocator protein can detect abnormal microglial activation (MA) in multiple sclerosis (MS). The objectives of this study are to develop individualized mapping of MA using18F-PBR06, to determine the effect of disease-modifying treatment (DMT) efficacy on reducing MA, and to determine its clinical, radiological, and serological correlates in MS patients.

Patients and Methods

Thirty18F-PBR06-PET scans were performed in 22 MS patients (mean age, 46 ± 13 years; 16 females) and 8 healthy controls (HCs). Logarithmically transformed “glial activity load on PET” scores (calculated as the sum of voxel-by-voxelz-scores ≥4), “lnGALP,” were compared between MS and HC and between MS subjects on high-efficacy DMTs (H-DMT, n = 13) and those on no or lower-efficacy treatment, and correlated with clinical measures, serum biomarkers, and cortical thickness.

Results

Cortical gray matter (CoGM) and white matter (WM) lnGALP scores were higher in MS versus HC (+33% and +48%,P< 0.001). In H-DMT group, CoGM and WM lnGALP scores were significantly lower than lower-efficacy treatment (P< 0.01) but remained abnormally higher than in HC group (P= 0.006). Within H-DMT patients, CoGM lnGALP scores correlated positively with physical disability, fatigue and serum glial fibrillary acid protein levels (r= 0.65–0.79, allP's < 0.05), and inversely with cortical thickness (r= −0.66,P< 0.05).

Conclusions

High-efficacy DMTs decrease, but do not normalize, CoGM and WM MA in MS patients. Such “residual” MA in CoGM is associated with clinical disability, serum biomarkers, and cortical degeneration. Individualized mapping of translocator protein PET using18F-PBR06 is clinically feasible and can potentially serve as an imaging biomarker for evaluating “smoldering” inflammation in MS patients.
Histomorphologic, Biomechanical, and Functional Analysis in Mandibular Osteogenesis Induced by External Distraction
Authors: Fuente-Del-Campo Antonio , Reyes Cureño Daniel
Published: April 2024

The induced bone generation procedure (osteogenic distraction [OD]) is frequently used in cases of jaw deformities in patients with, hemifacial microsomia, mandibular hypoplasia, and so on. This study was undertaken to provide criteria to perform this procedure. The authors evaluated the effects of various parameters using OD to determine the optimal variables. Sixty distractors were placed in 30 canine subjects who then underwent OD after appropriate osteotomy. The procedures were performed during varying latency periods, distraction periods, distraction rate distance, and the consolidation period. Bone biopsies and radiographic studies were performed at 0, 7, 14, 21, 45, and 55 days after the distraction process. The observed changes and the most efficient mandibular OD parameters are reported.
Visual and Pharmacotherapy Outcomes After Transverse Sinus Stenting for Idiopathic Intracranial Hypertension
Authors: Handzic Armin , Xie Jim Shenchu , Hendriks Eef , Mosimann Pascal , Nicholson Patrick , Micieli Jonathan , Margolin Edward
Published: April 2024

Background:

Transverse sinus stenting (TSS) is an increasingly common treatment for patients with idiopathic intracranial hypertension (IIH). However, detailed neuro-ophthalmic evidence on visual and pharmacotherapy outcomes after TSS is scarce and heterogeneous. This study aimed to describe the visual outcomes of patients undergoing TSS for IIH and to ascertain the proportion of patients who could be weaned off intracranial pressure (ICP)-lowering medication postoperatively.

Methods:

A retrospective chart review of all patients with IIH from 2 tertiary academic neuro-ophthalmology practices who underwent TSS between 2016 and 2022 was performed. Indications for stenting included failure of pharmacotherapy, intolerance of pharmacotherapy, and acute vision loss from severe papilledema. Data on demographics, symptoms, visual function, pharmacotherapy, and TSS were collected. The paired Wilcoxon rank sum test was used to compare changes in visual acuity (VA) and visual field mean deviation (VFMD) between the baseline and most recent visits.

Results:

Of the 435 patients with IIH, 15 (13 women) met inclusion criteria. After TSS, ICP-lowering pharmacotherapy was discontinued in 10 patients and decreased in 4; 1 patient was not on ICP-lowering medication before TSS. All patients experienced resolution or improvement of symptoms (10 resolution, 4 improved, 1 asymptomatic before TSS) and papilledema (11 resolution, 4 improved) after stenting. Papilledema resolution was confirmed with optical coherence tomography–measured peripapillary nerve fiber layer thickness (median decrease 147 µm, interquartile range 41.8–242.8 µm, P < 0.001). Change in VA between the baseline and most recent visit was not significant, but VFMD improved significantly after stenting (median increase 3.0, IQR 2.0–4.2, P < 0.001). No patient developed transverse sinus restenosis nor in-stent thrombosis postoperatively across a median venogram follow-up of 20.8 (11.3–49.8) weeks. In addition, no patient required subsequent surgical intervention for IIH.

Conclusions:

In this cohort of patients with IIH and fulminant presentation, medication resistance, or medication intolerance, TSS was an effective and safe treatment modality. Most patients were able to stop ICP-lowering medications while demonstrating striking improvement in symptomatology and visual function.
Alan Hall. 19 May 1952—3 May 2015
Authors: Machesky Laura M. , Jaffe Aron B. , Ridley FRS Anne J.
Published: April 2024

Alan Hall was born in a mining town in Yorkshire in 1952. He studied chemistry at Oxford and then, after starting his PhD in biochemistry in Oxford, he completed it at Harvard in the USA, where he made important discoveries about the evolution of antibiotic resistance in bacteria. Following postdoctoral studies in the UK and Switzerland, he set up his independent research in London at the Institute of Cancer Research, where he began his work which opened up the field of study of the Ras-homologous family of small GTPase proteins. Alan made seminal discoveries in this field, which revolutionized cell biology in the UK and internationally. Alan's work made connections between cell migration, cancer and cell signalling and provided a mechanistic understanding of how many cell processes work at the molecular level. Alan helped to found the Laboratory for Molecular Cell Biology in London and became the director in 2001. In 2006 he moved to the Memorial Sloan Kettering Cancer Center in New York as chair of Cell Biology. He was awarded the Feldberg Foundation Prize in 1993, the Novartis Medal (UK Biochemical Society) and the Louis Jeantet Prize for Medicine in 2005, as well as the Canada Gairdner Prize in 2006. He was elected as a European Molecular Biology Organization member in 1994, as a Fellow of the Royal Society in 1999 and Fellow of the Academy of Medical Sciences in 2004.
Weak effect of urbanization on bdelloid rotifers living in lichens
Authors: Partemi Rebecca , Debortoli Nicolas , Martínez Alejandro , Kamburska Lyudmila , Souffreau Caroline , Matheve Hans , Vantieghem Pieter , De Meester Luc , Van Doninck Karine , Merckx Thomas , Fontaneto Diego
Published: April 2024

Human activities have an overwhelming impact on the natural environment, leading to a deep biodiversity crisis whose effects range from genes to ecosystems. Here, we analysed the effect of such anthropogenic impacts on bdelloid rotifers (Rotifera Bdelloidea), for whom these effects are poorly understood. We targeted bdelloid rotifers living in lichen patches across urbanization gradients in Flanders and Brussels (Belgium). Urbanization was measured as the percentage of built-up area (BU) across different spatial scales, at circles from 50 to 3200 m of radius around the lichen. Urbanization effects on biodiversity were assessed on abundance, species richness and community-weighted mean body size of bdelloid rotifers, as well as on genetic diversity of a mitochondrial marker (cytochrome
c
oxidase subunit I) of one of the most common and widespread bdelloid species,
Adineta vaga
. Overall, no negative effect of urbanization was found at any diversity level and any spatial scale. Counterintuitively, the BU area quantified at the largest spatial scale had a positive effect on abundance. These results leave open the question of whether negative effects of urbanization are present for bdelloid rotifers, if they are mediated by other unexplored drivers, or if such effects are only visible at even larger spatial scales.
Social restructuring during harsh environmental conditions promotes cooperative behaviour in a songbird
Authors: Camerlenghi Ettore , Nolazco Sergio , Farine Damien R. , Magrath Robert D. , Peters Anne
Published: April 2024

Cooperation may emerge from intrinsic factors such as social structure and extrinsic factors such as environmental conditions. Although these factors might reinforce or counteract each other, their interaction remains unexplored in animal populations. Studies on multilevel societies suggest a link between social structure, environmental conditions and individual investment in cooperative behaviours. These societies exhibit flexible social configurations, with stable groups that overlap and associate hierarchically. Structure can be seasonal, with upper-level units appearing only during specific seasons, and lower-level units persisting year-round. This offers an opportunity to investigate how cooperation relates to social structure and environmental conditions. Here, we study the seasonal multilevel society of superb fairy-wrens (
Malurus cyaneus
), observing individual responses to experimental playback of conspecific distress calls. Individuals engaged more in helping behaviour and less in aggressive/territorial song during the harsher non-breeding season compared to the breeding season. The increase in cooperation was greater for breeding group members than for members of the same community, the upper social unit, comprised of distinct breeding groups in association. Results suggest that the interaction between social structure and environmental conditions drives the seasonal switch in cooperation, supporting the hypothesis that multilevel societies can emerge to increase cooperation during harsh environmental conditions.
Invasibility of a North American soil ecosystem to amphibian-killing fungal pathogens
Authors: McGrath-Blaser Sarah E. , McGathey Natalie , Pardon Allison , Hartmann Arik M. , Longo Ana V.
Published: April 2024

North American salamanders are threatened by intercontinental spread of chytridiomycosis, a deadly disease caused by the fungal pathogenBatrachochytrium salamandrivorans(Bsal). To predict potential dispersal ofBsalspores to salamander habitats, we evaluated the capacity of soil microbial communities to resist invasion. We determined the degree of habitat invasibility using soils from five locations throughout the Great Smoky Mountains National Park, a region with a high abundance of susceptible hosts. Our experimental design consisted of replicate soil microcosms exposed to different propagule pressures of the non-native pathogen,Bsal, and an introduced but endemic pathogen,B. dendrobatidis(Bd). To compare growth and competitive interactions, we used quantitative PCR, live/dead cell viability assays, and full-length 16S rRNA sequencing. We found that soil microcosms with intact bacterial communities inhibited bothBsalandBdgrowth, but inhibitory capacity diminished with increased propagule pressure.Bsalshowed greater persistence thanBd. Linear discriminant analysis (LDA) identified the family Burkolderiaceae as increasing in relative abundance with the decline of both pathogens. Although our findings provide evidence of environmental filtering in soils, such barriers weakened in response to pathogen type and propagule pressure, showing that habitats vary their invasibility based on properties of their local microbial communities.
Small skeletons show size-specific scaling: an exploration of allometry in the mammalian lumbar spine
Authors: Smith S. M. , Heaney L. R. , Angielczyk K. D.
Published: April 2024

Studies of vertebrate bone biomechanics often focus on skeletal adaptations at upper extremes of body mass, disregarding the importance of skeletal adaptations at lower extremes. Yet mammals are ancestrally small and most modern species have masses under 5 kg, so the evolution of morphology and function at small size should be prioritized for understanding how mammals subsist. We examined allometric scaling of lumbar vertebrae in the small-bodied Philippine endemic rodents known as cloud rats, which vary in mass across two orders of magnitude (15.5 g–2700 g). External vertebral dimensions scale with isometry or positive allometry, likely relating to body size and nuances in quadrupedal posture. In contrast to most mammalian trabecular bone studies, bone volume fraction and trabecular thickness scale with positive allometry and isometry, respectively. It is physiologically impossible for these trends to continue to the upper extremes of mammalian body size, and we demonstrate a fundamental difference in trabecular bone allometry between large- and small-bodied mammals. These findings have important implications for the biomechanical capabilities of mammalian bone at small body size; for the selective pressures that govern skeletal evolution in small mammals; and for the way we define ‘small’ and ‘large’ in the context of vertebrate skeletons.
The importance of migratory drop-off for island colonization in birds
Authors: Dufour Paul , Sayol Ferran , Cooke Rob , Blackburn Tim M. , Gallien Laure , Griesser Michael , Steinbauer Manuel J. , Faurby Søren
Published: April 2024

Seasonal migration is an underappreciated driver of animal diversification. Changes in migratory behaviour may favour the establishment of sedentary founder populations and promote speciation if there is sufficient reproductive isolation between sedentary and migratory populations. From a systematic literature review, we here quantify the role of migratory drop-off—the loss of migratory behaviour—in promoting speciation in birds on islands. We identify at least 157 independent colonization events likely initiated by migratory species that led to speciation, including 44 cases among recently extinct species. By comparing, for all islands, the proportion of island endemic species that derived from migratory drop-off with the proportion of migratory species among potential colonizers, we showed that seasonal migration has a larger effect on island endemic richness than direct dispersal. We also found that the role of migration in island colonization increases with the geographic isolation of islands. Furthermore, the success of speciation events depends in part on species biogeographic and ecological factors, here positively associated with greater range size and larger flock sizes. These results highlight the importance of shifts in migratory behaviour in the speciation process and calls for greater consideration of migratory drop-off in the biogeographic distribution of birds.
Association between the gut microbiome and carotenoid plumage phenotype in an avian hybrid zone
Authors: Baiz Marcella D. , Wood Andrew W. , Toews David P. L.
Published: April 2024

Vertebrates host complex microbiomes that impact their physiology. In many taxa, including colourful wood-warblers, gut microbiome similarity decreases with evolutionary distance. This may suggest that as host populations diverge, so do their microbiomes, because of either tight coevolutionary dynamics, or differential environmental influences, or both. Hybridization is common in wood-warblers, but the effects of evolutionary divergence on the microbiome during secondary contact are unclear. Here, we analyse gut microbiomes in two geographically disjunct hybrid zones between blue-winged warblers (Vermivora cyanoptera) and golden-winged warblers (Vermivora chrysoptera). We performed 16S faecal metabarcoding to identify species-specific bacteria and test the hypothesis that host admixture is associated with gut microbiome disruption. Species identity explained a small amount of variation between microbiomes in only one hybrid zone. Co-occurrence of species-specific bacteria was rare for admixed individuals, yet microbiome richness was similar among admixed and parental individuals. Unexpectedly, we found several bacteria that were more abundant among admixed individuals with a broader deposition of carotenoid-based plumage pigments. These bacteria are predicted to encode carotenoid biosynthesis genes, suggesting birds may take advantage of pigments produced by their gut microbiomes. Thus, host admixture may facilitate beneficial symbiotic interactions which contribute to plumage ornaments that function in sexual selection.
Deep learning methods in metagenomics: a review
Authors: Roy Gaspar , Prifti Edi , Belda Eugeni , Zucker Jean-Daniel
Published: April 2024

The ever-decreasing cost of sequencing and the growing potential applications of metagenomics have led to an unprecedented surge in data generation. One of the most prevalent applications of metagenomics is the study of microbial environments, such as the human gut. The gut microbiome plays a crucial role in human health, providing vital information for patient diagnosis and prognosis. However, analysing metagenomic data remains challenging due to several factors, including reference catalogues, sparsity and compositionality. Deep learning (DL) enables novel and promising approaches that complement state-of-the-art microbiome pipelines. DL-based methods can address almost all aspects of microbiome analysis, including novel pathogen detection, sequence classification, patient stratification and disease prediction. Beyond generating predictive models, a key aspect of these methods is also their interpretability. This article reviews DL approaches in metagenomics, including convolutional networks, autoencoders and attention-based models. These methods aggregate contextualized data and pave the way for improved patient care and a better understanding of the microbiome’s key role in our health.
Instruction Alters the Influence of Allocentric Landmarks in a Reach Task
Authors: Musa Lina , Yan Xiaogang , Crawford J. Douglas
Published: April 2024

Allocentric landmarks have an implicit influence on aiming movements, but it is not clear how an explicit instruction (to aim relative to a landmark) influences reach accuracy and precision. Here, 12 participants performed a task with two instruction conditions (egocentricvs.allocentric), but with similar sensory and motor conditions. Participants fixated gaze near the centre of a display aligned with their right shoulder while a target stimulus briefly appeared alongside a visual landmark in one visual field. After a brief mask/memory delay the landmark then re-appeared at a different location (same or opposite visual field), creating an ego/allocentric conflict. In theegocentriccondition, participants were instructed to ignore the landmark and point towards the remembered location of the target. In theallocentriccondition, participants were instructed to remember the initial target location relative to the landmark and then reach relative to the shifted landmark (same/opposite visual field). To equalize motor execution between tasks, participants were instructed to anti-point (point to the visual field opposite to the remembered target) on 50 % of the egocentric trials. Participants were more accurate, precise, and quicker to react in the allocentric condition, especially when pointing to the opposite field. We also observed a visual field effect, where performance was worse overall in the right visual field. These results suggest that when egocentric and allocentric cues conflict, explicit use of the visual landmark provides better reach performance than reliance on noisy egocentric signals. Such instructions might aid rehabilitation when the egocentric system is compromised by disease or injury.

Highlights

12 participants reached to remembered targets in the presence of a visual landmark

Participants were instructed to ignore, or point relative to, the landmark

The landmark instruction improved reaction time, precision, and accuracy

These effects were stronger when pointing was cued toward the opposite visual field

Knowledge of these rules might be used to enhance performance or in rehabilitation