bluuebunny/crossref_metadata_2025 huggingface dataset:
Japan and the liberal international order: rules-based, multilateral, inclusive and localized
Authors: Nakano Ryoko
Published: June 2023

This article examines Japan's security and foreign policy as an example of how a major power engages in the liberal international order (LIO) and what this implies for the future of that order. Facing China's increased power and influence in the past two decades, Japan has made strategic adjustments in response to regional and global power transitions while developing an idea of a wider geopolitical landscape on Prime Minister Shinzo Abe's initiative. However, this article argues that Japan's idea of an expanded regional scope and its vision of order were addressed decades earlier through ‘comprehensive security’ (sogo anzen hosho). While the country is an ally of the United States and clearly accepts the alliance as a key part of international order, Japan has its own ideas about international order; these accept much of the LIO but go beyond it, particularly in the articulation and operationalization of comprehensive security. By adopting the concept of norm localization, this article argues that Japan does not have the power to coerce others to take any actions to defend the current international order, but it can adapt and tweak the dominant LIO norms, principles and practices to build congruence with local norms of sovereignty and territorial integrity embedded in its own region. To create a broader consensus in favour of sustaining the LIO, major powers like Japan can approach the sceptics by presenting an alternative to either total rejection or total acceptance of the LIO norms.
Ceratal autotomy as a defensive mechanism of the sacoglossan sea slug Placida kingstoni against a generalist crustacean predator
Authors: Gutierrez-Andrade D , Middlebrooks M L
Published: June 2023

Sacoglossan sea slugs have developed a variety of defence mechanisms against predation. Research on these mechanisms has focused primarily on the chemical defences of these slugs, and little information is available on nonchemical modes of defence, such as autotomy, a behaviour in which an organism voluntarily detaches body structures at a predetermined breakage point in response to danger or stress. Autotomy is diverse in sacoglossan sea slugs and has been well documented. Within Oxynidae, members can autotomize their tail and parapodial lobes, and slugs in Limapontiidae and Hermaeidae can detach their cerata. More recently, reports have been made of Elysia with the capacity to autotomize most of their body. However, despite the widespread assumption that autotomy in this group serves a defensive purpose, the effectiveness of the behaviour in ensuring survival against predation has seldom been examined. The objective of this study was to evaluate the role of autotomy in sacoglossans by assessing the effectiveness of ceratal autotomy in ensuring survival against the attacks of a generalist predator. Placida kingstoni is a small sacoglossan native to Florida and the Caribbean with the ability to autotomize its cerata. Individual P. kingstoni were exposed to shrimps of the Lysmata wurdemanni species complex for 10-min interactions. Most sea slugs were attacked by the predator, often more than once, but the majority of the slugs readily autotomized cerata and survived. Structure detachment was accompanied by the secretion of a mucus that facilitated the formation of ceratal clumps. Most of these clumps were consumed by the predator and effectively diverted their attention, allowing P. kingstoni to crawl away. In this species, the success of autotomy as a defensive strategy appears to be directly related to the palatability of autotomized cerata. The results of this study show that ceratal autotomy in P. kingstoni is an effective defence against predation. Autotomy is a behaviour with a high-energetic cost; however, it has convergently evolved within Heterobranchia on multiple occasions, and it is highly prevalent in cerata-bearing slugs. Although in sacoglossans much of this behaviour remains a mystery, this study provides a clear example of autotomy as a defensive mechanism.
Stenocarpella chrysopogonis, a New Species Causing Leaf Streak Disease of Chrysopogon zizanioides in Southern China
Authors: Jia Xitao , Zheng Xie , Damm Ulrike , Lu Xiang , Niu Xueli , Feng Yufei , Zhang Wu
Published: June 2023

Vetiver grass (Chrysopogon zizanioides) has been widely used in recent years for ecological environment management, restoration of degraded ecosystems, and essential oil extraction. In 2019, a leaf streak disease of C. zizanioides was observed in Zhanjiang, Guangdong Province, China. The disease appeared as large streak lesions on the leaves, on which conidiomata were formed. A pathogenicity test with the fungus isolated from these lesions confirmed Koch’s postulates and thus the fungus as the causal agent of this disease. A morphological resemblance of the pathogen to Stenocarpella was noted upon microscopic examination. Phylogenetic trees inferred from both individual and combined ITS, LSU, and tef1 sequences confirmed the pathogen as a species of the Diaporthaceae and revealed it to be closely related to Phaeocytostroma and Stenocarpella species. As morphological characters clearly placed the pathogen in the genus Stenocarpella, it was described as S. chrysopogonis.
Flexor Pollicis Tendon Reconstruction With Allograft Tendon After Rupture: Technique and Case Series
Authors: Townsley Sarah H. , Shin Alexander Y.
Published: June 2023

Division or rupture of the flexor pollicis longus (FPL) tendon can occur secondary to direct injury, laceration, or attritional rupture. Attritional rupture is particularly common in the setting volar plate fixation of a distal radius fracture. FPL tendon discontinuity can be restored through either primary repair or reconstruction. Primary repair can be challenging if not done within the first few days after injury secondary to contraction of the FPL muscle with retraction of the proximal tendon. Repair in this environment can lead to tension across the repair site as well as necessary flexion of the interphalangeal joint to accommodate primary repair. In the setting of attritional rupture, the proximal and distal ends are typically not viable for direct repair. We present our preferred technique for restoration of the FPL tendon, which is reconstruction with an allograft tendon.
Analysis of circulating tumor DNA during checkpoint inhibition in metastatic melanoma using a tumor-agnostic panel
Authors: Kisistók Judit , Christensen Ditte Sigaard , Rasmussen Mads Heilskov , Duval Lone , Aggerholm-Pedersen Ninna , Luczak Adam Andrzej , Sorensen Boe Sandahl , Jakobsen Martin Roelsgaard , Oellegaard Trine Heide , Birkbak Nicolai Juul
Published: June 2023

Immunotherapy has revolutionized treatment of patients diagnosed with metastatic melanoma, where nearly half of patients receive clinical benefit. However, immunotherapy is also associated with immune-related adverse events, which may be severe and persistent. It is therefore important to identify patients that do not benefit from therapy early. Currently, regularly scheduled CT scans are used to investigate size changes in target lesions to evaluate progression and therapy response. This study aims to explore if panel-based analysis of circulating tumor DNA (ctDNA) taken at 3-week intervals may provide a window into the growing cancer, can be used to identify nonresponding patients early, and determine genomic alterations associated with acquired resistance to checkpoint immunotherapy without analysis of tumor tissue biopsies. We designed a gene panel for ctDNA analysis and sequenced 4–6 serial plasma samples from 24 patients with unresectable stage III or IV melanoma and treated with first-line checkpoint inhibitors enrolled at the Department of Oncology at Aarhus University Hospital, Denmark. TERT was the most mutated gene found in ctDNA and associated with a poor prognosis. We detected more ctDNA in patients with high metastatic load, which indicates that more aggressive tumors release more ctDNA into the bloodstream. Although we did not find evidence of specific mutations associated with acquired resistance, we did demonstrate in this limited cohort of 24 patients that untargeted, panel-based ctDNA analysis has the potential to be used as a minimally invasive tool in clinical practice to identify patients where the benefits of immunotherapy outweigh the drawbacks.
A Rare Case of Complete Sequestration of the Patella: an Unusual Presentation of Patellar Tuberculosis
Authors: Thakkar Samarth , Hegde Atmananda , Mane Prajwal , Shetty Chethan , Tripathi Anshul
Published: June 2023

Osteoarticular tuberculosis affecting the knee with isolated involvement of the patella is rare, accounting for less than 0.09% to 0.15% of cases. We present a case of 48-year-old man presenting with chronic knee swelling, pain, and stiffness. Radiographs revealed a completely sclerotic patella with erosions and irregular margins. Magnetic resonance imaging revealed chronic synovitis, joint effusion, and bony erosions with full-thickness cartilage defects in the patella. He underwent surgical debridement with extensive synovectomy, and a total patellectomy was performed. Intraoperative samples conclusively diagnosed it as a tubercular infection of the patella and synovium. The patient was started on antitubercular chemotherapy. A 2-year follow-up revealed good knee function with an extensor lag of 100. There has been no recurrence of infection. This report is a rare case of complete patellar sequestration secondary to tuberculosis patella, which was successfully treated with radical debridement and patellectomy.
Influence of endotamponade on anterior chamber depth and refractive outcome after combined phacovitrectomy: case-control study
Authors: Chatzimichail Eleftherios , Wertheimer Christian , Kilani Adnan , König Susanna , Gatzioufas Zisis , Wolf Armin , Vounotrypidis Efstathios
Published: June 2023

Purpose:

To compare the changes in the anterior chamber depth (ACD) and in the refractive outcomes after combined phacovitrectomy with respect to the endotamponade (balanced salt solution, air, sulfur hexafluoride [SF6, gas]).

Setting:

Department of Ophthalmology, University Hospital Ulm, Ulm, Germany.

Design:

Retrospective, longitudinal case-control study.

Methods:

160 eyes of 160 patients were included in the study. 120 eyes underwent phacoemulsification with in-the-bag implantation combined with vitrectomy and were divided into 3 groups according to tamponade (balanced salt solution, air, gas). 40 control eyes with cataract surgery only were included. Further inclusion criteria were uneventful surgery, no postoperative complications and absence of corneal pathology. Endpoints were ACD as measured by swept-source optical coherence tomography-based biometry (IOLMaster 700) preoperatively, 1 to 2 days and 6 weeks postoperatively and refractive prediction error (PE) using the Barrett and Haigis formulas.

Results:

Within the first 2 days after surgery the ACD was shallower in the eyes left with gas or air tamponade, when compared with balanced salt solution or cataract surgery alone (P < .001). This effect diminished 6 weeks later, and all eyes reached comparable ACD (P = .396). The refractive PE was slightly, but statistically significantly higher in the gas group when compared with cataract surgery alone (P = .012 for Barrett, P = .006 for Haigis).

Conclusions:

The resulting ACD after combined phacovitrectomy was independent of the tamponade used, but a gas-tamponade was associated with a higher refractive PE.
Immediate sequential vs delayed sequential bilateral cataract surgery: systematic review and meta-analysis
Authors: Aiello Francesco , Gallo Afflitto Gabriele , Leviste Katherine , Swaminathan Swarup S. , Yoo Sonia H. , Findl Oliver , Maurino Vincenzo , Nucci Carlo
Published: June 2023

The main aim of this systematic review and meta-analysis was to evaluate the safety and efficacy profile of immediate sequential bilateral cataract surgery (ISBCS) compared with delayed sequential bilateral cataract surgery (DSBCS). MEDLINE Ovid, EMBASE, and CENTRAL databases were searched. Outcome measures were postoperative visual acuity, postoperative spherical equivalent (refractive outcome), endophthalmitis, corneal edema, pseudophakic macular edema, and posterior capsule rupture (PCR). 13 articles met criteria for final inclusion. A total of 11 068 622 participants (18 802 043 eyes) were included. No statistically significant differences between ISBCS and DSBCS were identified in all the postoperative outcomes evaluated. However, a higher risk for PCR was identified in the ISBCS group from the pooled analysis of nonrandomized studies (risk ratio, 1.34, 95% CI, 1.08-1.67, P = .0081). In our view, the ISBCS approach has an acceptable safety-efficacy profile, comparable with DSBCS. Future investigations are warranted, with a focus on the analysis of risk factors for surgical complications, patient-reported outcome-measures, and cost effectiveness.
Subcutaneous versus intravenous tramadol for extremity injury with moderate pain in the emergency department: a randomised controlled noninferiority trial
Authors: Bustam Aida , Poh Khadijah , Zambri Aliyah , Mohd Nazri Mohd Zahir Amin , Subramaniam Thayaharan , Abdullah Adlina Athilah , Nor Azman Amyrul Ikmal Haziq , Ang Bin Ting , Noor Azhar Abdul Muhaimin
Published: June 2023

Background and importance

Musculoskeletal trauma is a common presentation in the emergency department (ED). Tramadol as an analgesic has been recommended by pain management guidelines for musculoskeletal pain. Parenteral tramadol in the ED is commonly administered intravenously. Subcutaneously administered tramadol may have other advantages such as easier and faster preparation, avoids the need for intravenous (i.v.) access, and reduces the incidence of respiratory and gastrointestinal effects. However, studies comparing subcutaneous (s.c.) and i.v. tramadol for the management of acute moderate pain in patients with extremity injury are lacking.

Objective

The objective of this study was to compare the clinical efficacy of s.c. tramadol vs. i.v. tramadol in patients with moderate pain due to extremity injury in the ED.

Design, settings, and participants

This non-inferiority randomized controlled trial included adult patients presented to an academic, tertiary hospital ED with moderate pain (pain score of 4–6 on the visual analog scale) due to extremity injury. Intervention patients stratified to pain score were randomized to receive 50 mg of i.v. or s.c. tramadol.

Outcomes measure and analysis

Primary outcome measure was the difference in the pain score reduction at 30 min after tramadol administration between the two groups. The noninferiority null hypothesis was that the therapeutic difference in terms of pain score reduction of more than 0.8 exists between the two treatment groups at the endpoint.

Main results

In total 232 patients were randomized to i.v. (n = 115) or s.c. (n = 117). Although 225 were analyzed in the per-protocol population (i.v. = 113; s.c. = 112). The baseline median pain score was 6 (IQR, 5–6). Median pain score reduction at 30 min after administration was 2 (IQR, 1–3) in the IV group vs. 2 (IQR, 1–2) in the s.c. group with a median difference of 0 (IQR, 0–0), which was below the prespecified noninferiority margin of 0.8. Adverse events in the i.v. group were higher compared to the s.c. group (33.6% vs. 8.9%, P ≤ 0.001).

Conclusions

The s.c. tramadol is noninferior to i.v. tramadol in the treatment of moderate pain from extremity injuries.
Interobserver Agreement on the Interpretation of Programmed Death-ligand 1 (PD-L1) Combined Positive Score (CPS) Among Gynecologic Pathologists
Authors: Mills Anne M. , Bennett Jennifer A. , Banet Natalie , Watkins Jaclyn C. , Kundu Debamita , Pinto Andre
Published: June 2023

The anti-programmed cell death (PD-1) checkpoint inhibitor pembrolizumab is approved for the treatment of cervical carcinoma with a programmed cell death-ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1. We assessed interobserver agreement in cervical carcinoma PD-L1 CPS to identify whether it may affect patient selection for immunotherapeutic candidacy. Twenty-nine cervical carcinomas were stained for PD-L1 (Dako 22C3), and slides were interpreted by 5 subspecialty-trained gynecologic pathologists with experience reading PD-L1 immunohistochemistry. Expression was scored using CPS and read out as positive (≥1) or negative (<1); in positive cases, a final score was assigned (1 to 100). There was consensus agreement across all 5 pathologists for 90% (26/29) (Fleiss Kappa value for interobserver agreement: 0.799). The 3 cases with disagreement were composed of 2 squamous cell carcinomas and 1 small cell carcinoma. Of the 26 with unanimous agreement, 88% (23/26) were positive and 12% (3/26) were negative. All (16/16) pure squamous cell carcinomas with full consensus were interpreted as positive, whereas tumors with glandular components were commonly consensus negative (33%, 3/9); this difference was significant (P=0.037). Disagreements were attributable to low CPS versus negative reads (2 cases) and difficulty discerning glandular involvement from pushing invasion (1 case). In summary, experienced gynecologic pathologists showed substantial interobserver agreement in the interpretation of PD-L1 CPS at the Food and Drug Administration–approved treatment threshold, with the majority of tumors being classified as positive. Pure squamous histology was strongly associated with a consensus-positive read, whereas a subset of tumors with glandular differentiation was negative by all readers. Disagreements occurred in tumors with low versus negative CPS values and in the setting of limited invasion.
Derivation, Validation, and Clinical Relevance of a Pediatric Sepsis Phenotype With Persistent Hypoxemia, Encephalopathy, and Shock*
Authors: Sanchez-Pinto L. Nelson , Bennett Tellen D. , Stroup Emily K. , Luo Yuan , Atreya Mihir , Bubeck Wardenburg Juliane , Chong Grace , Geva Alon , Faustino E. Vincent S. , Farris Reid W. , Hall Mark W. , Rogerson Colin , Shah Sareen S. , Weiss Scott L. , Khemani Robinder G.
Published: June 2023

OBJECTIVES:

Untangling the heterogeneity of sepsis in children and identifying clinically relevant phenotypes could lead to the development of targeted therapies. Our aim was to analyze the organ dysfunction trajectories of children with sepsis-associated multiple organ dysfunction syndrome (MODS) to identify reproducible and clinically relevant sepsis phenotypes and determine if they are associated with heterogeneity of treatment effect (HTE) to common therapies.

DESIGN:

Multicenter observational cohort study.

SETTING:

Thirteen PICUs in the United States.

PATIENTS:

Patients admitted with suspected infections to the PICU between 2012 and 2018.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

We used subgraph-augmented nonnegative matrix factorization to identify candidate trajectory-based phenotypes based on the type, severity, and progression of organ dysfunction in the first 72 hours. We analyzed the candidate phenotypes to determine reproducibility as well as prognostic, therapeutic, and biological relevance. Overall, 38,732 children had suspected infection, of which 15,246 (39.4%) had sepsis-associated MODS with an in-hospital mortality of 10.1%. We identified an organ dysfunction trajectory-based phenotype (which we termed persistent hypoxemia, encephalopathy, and shock) that was highly reproducible, had features of systemic inflammation and coagulopathy, and was independently associated with higher mortality. In a propensity score-matched analysis, patients with persistent hypoxemia, encephalopathy, and shock phenotype appeared to have HTE and benefit from adjuvant therapy with hydrocortisone and albumin. When compared with other high-risk clinical syndromes, the persistent hypoxemia, encephalopathy, and shock phenotype only overlapped with 50%–60% of patients with septic shock, moderate-to-severe pediatric acute respiratory distress syndrome, or those in the top tier of organ dysfunction burden, suggesting that it represents a nonsynonymous clinical phenotype of sepsis-associated MODS.

CONCLUSIONS:

We derived and validated the persistent hypoxemia, encephalopathy, and shock phenotype, which is highly reproducible, clinically relevant, and associated with HTE to common adjuvant therapies in children with sepsis.
Characteristics of Transport of Ill Pediatric Patients in the Emergency Department
Authors: Yock-Corrales Adriana , Curto Danila Andrea , Gerolami Andrea , Mota Cesar , Vigna Andrés , Camacho Edgardo , González-Vallejos Silvia Catalina , Copana-Olmos Raúl , Gómez-Vargas Jessica , Cassón Nils ,   On Behalf of the Transport Working Group of the Red de Investigación y Desarrollo de la Emergencia Pediátrica Latinoamericana (RIDEPLA)
Published: June 2023

Objective

The aim was to describe the characteristics of the transport system of critically ill pediatric patients in the emergency departments (EDs) in Latin America (LA).

Methodology

This is a prospective cross-sectional study in a 1-year period. Patients were recruited on days 1, 7, 14, 21, and 28 of each month in the EDs in LA. We included ill-pediatric patients aged 1 month to 18 years. Patients who needed transfer for a diagnostic study, with arrival mode not by ambulance, or with the impossibility of interviewing the transfer team were excluded from the study.

Results

A total of 389 patients were included in the study. The majority were males (57%) with a median age of 49 months (interquartile range, 10–116). Thirty-three percent (129) of transfers had the participation of a coordinating center; 97.1% (375) were carried out by road ambulance, and 84.3% (323) were interhospital transfers, with a mean distance traveled of 83.2 km (SD, 105 km). The main reason for transfer in 88.17% (343) was the need for a more complex health center. The main diagnosis was respiratory distress (71; 18.2%), acute abdomen (70; 18%), Traumatic Brain Injury (33; 8.48%), multiple trauma (32; 8.23%), septic shock (31; 7.9%), and COVID-19–related illness (19; 4.8%). A total of 296 (76.5%) patients had peripheral vascular access, and 171 (44%) patients had oxygen support with 49 (28.6%) having invasive ventilation; the most frequent monitoring method (67.8%) was pulse oximetry, and 83.4% (313) did not record adverse events. Regarding the transfer team, 88% (342) had no specialized personnel, and only 62.4% (243) had a physician on their teams.

Conclusions

In LA, there is great variability in personnel training, equipment for pediatric transport, team composition, and characterization of critical care transport systems. Continued efforts to improve conditions in our countries may help reduce patient morbidity and mortality.
Regional Anesthesia as an Alternative to Procedural Sedation for Forearm Fracture Reductions in the Pediatric Emergency Department
Authors: Sulton Carmen D. , Fletcher Nicholas , Murphy Joshua , Gillespie Scott , Burger Rebecca K.
Published: June 2023

Background

Pediatric forearm fractures are common injuries in the pediatric emergency department (PED). Pediatric procedural sedation (PPS) is often required for forearm fracture reductions and pain control for casting. Bier blocks and hematoma blocks are types of regional anesthesia (RA) procedures that can be performed as a potential alternative to PPS.

Objective

The objective of this study is to compare the safety of RA with that of PPS. We hypothesized that RA has a safety profile that is equal or superior to PPS as well as a shorter duration of treatment in the PED.

Methods

Pediatric emergency department encounters in patients presenting with a diagnosis of radius fracture, ulna fracture, distal “both-bone” fracture, Monteggia fracture, and/or Galeazzi fracture were included. Outcomes of interest included patient adverse events (AEs), sedation medications used, PED duration of treatment (arrival time to disposition time), sedation failures, and reduction failures.

Results

Propensity matching was performed resulting in 632 well-matched RA-PPS pairs. The PPS cohort had 13% of encounters with at least 1 AE compared with 0.2% in the RA cohort, P < 0.001. The most common AE in the PPS group was hypoxia (9.8%), and the only AE in the RA group was an intravenous infiltrate (0.16%). Within the matched cohorts, PPS required more medications than RA (100% vs 60%, P < 0.001). Ketamine alone was more commonly used in the PPS group than the RA group (86% vs 0.2%, P < 0.001). Propofol was used only in the PPS group. The average duration of treatment was 205 (SD, 81) minutes in the PPS group and 178 (SD, 75) minutes in the RA group (P < 0.001). There were no reduction failures in either group.

Conclusions

Bier blocks and hematoma blocks are an acceptable alternative to PPS for children requiring forearm reductions. The AE rate is low and the reduction success rate is high. Duration of treatment in the PED is shorter for patients receiving RA compared with PPS.
Evaluation of Glomerular Filtration Rate Trends in People Living With HIV Corrected by the Baseline Glomerular Filtration Rate
Authors: Reis Amanda Orlando , Rocco Suassuna José H. , Cunha Cynthia B. , Portela Estevão N. , Veloso Valdilea G. , Grinszteijn Beatriz , Cardoso Sandra Wagner
Published: June 2023

Background:

Chronic kidney disease, for which estimated glomerular filtration rate (eGFR) trajectories are early markers, is frequent in people living with HIV.

Setting:

Identify eGFR trajectory patterns according to kidney function and assess associated factors over a 13-year follow-up period.

Methods:

We evaluated longitudinal changes and its associated factors in eGFR of 3366 participants according to kidney function with a 2-level, linear, mixed model.

Results:

Participants with initial kidney dysfunction experienced a slight eGFR increase, whereas others showed a slight decrease. A weak relationship was observed between baseline eGFR and its variation over time. Baseline eGFR was affected by age, CD4+ count, viral load, hypertension, hyperlipidemia, AIDS-defining illness and tenofovir (TDF) with integrase inhibitor (INSTI) or efavirenz. Significant factors for eGFR change included the following: in kidney dysfunction, CD4+ cell count of >350 cells per cubic millimeter and undetectable viral load increased eGFR, whereas TDF + protease inhibitor decreased eGFR; in mildly decreased kidney function, CD4+ cell count of >350 cells per cubic millimeter, AIDS-defining illness, and TDF + efavirenz increased eGFR, whereas age, hypertension, hyperlipidemia, and TDF + INSTI decreased eGFR; in normal kidney function, age, CD4+ cell count of > 350 cells per cubic millimeter, undetectable viral load, hypertension, hyperlipidemia, and TDF + INSTI decreased eGFR, whereas TDF + efavirenz increased eGFR (all P value for interaction < 0.05).

Conclusion:

Our findings suggest that eGFR trajectories varied widely between individuals in people living with HIV. In the lower eGFR group, virus-related factors were more relevant, whereas traditional risk factors for renal dysfunction were more prominent in the highest eGFR group.
Relapsing Polychondritis
Authors: Kwok Sing Hon , Choi Frankie
Published: June 2023

We present a 54-year-old woman with 3-month history of skin rash and bilateral hearing loss. Multiple investigations including biopsy failed to reveal the underlying diagnosis of relapsing polychondritis, until 18F-FDG PET/CT demonstrated a characteristic FDG activity pattern—the oto-rhino-tracheobronchial triad. The patient was subsequently diagnosed to have relapsing polychondritis and received treatment. The second FDG PET/CT revealed a differential response in different disease sites, which prompted an escalation of treatment.
Simultaneous Heart-kidney Transplant With Planned Delayed Implantation of the Kidney Graft After Ex Vivo Perfusion
Authors: Lutz Andrew J. , Nagaraju Santosh , Sharfuddin Asif A. , Garcia Jose P. , Saleem Kashif , Mangus Richard S. , Goggins William C.
Published: June 2023

Background.

Simultaneous heart-kidney transplant (SHK) is an established option for patients with severe heart failure and chronic kidney disease. Recent studies in simultaneous liver-kidney transplantation demonstrate favorable outcomes achieved by delaying implantation of the kidney for over 24 h. This report describes a case series of consecutive patients listed for SHK who had planned delayed implantation of the kidney graft.

Methods.

This case series represents a retrospective analysis of SHK patients extracted from the transplant database at a single center.

Results.

There were 7 patients who underwent SHK during the study period. In all cases, kidney grafts were maintained on hypothermic ex vivo pulsatile perfusion for delayed implantation (mean cold ischemia 53 h [range, 31–69]). The first 5 patients had 100% 1-y heart and kidney graft survival with good function. Patient 6 was unstable on extracorporeal membrane oxygenation post–heart transplant. The kidney was implanted at 69 h, and the patient died soon thereafter. Patient 7 was also unstable on extracorporeal membrane oxygenation after heart transplant. The decision was made to implant the kidney into a backup kidney recipient. The heart transplant recipient subsequently died several days later, whereas the kidney was successfully transplanted in the alternate candidate.

Conclusions.

This case series highlights the potential utility of delayed kidney implantation in SHK patients. SHK with delayed renal transplant may provide an improved physiologic environment for renal transplant, which may result in improved early renal graft function. Delayed kidney transplant also provides the opportunity to transplant the kidney graft into an alternate candidate.
OrthoFx Rescue Aligner: A Mid-Course Correction during Orthodontic Clear Aligner Therapy
Authors: Chwa Evan , Alqazaha Tamara , Sanchez Flavio José Castelli , Kusnoto Budi , Elnagar Mohammed H.
Published: June 2023

Over the last few decades, there has been a significant increase in the number of patients seeking orthodontic treatment due to the esthetics of clear aligners. However, clear aligners rely on accurate tracking and if not achieved, can lead to frustrations.

Data from 60 comprehensive clear aligner patients were analyzed. The OrthoFX Rescue Aligner intervened in the cases that were not tracking to get the patient back on track. The Rescue Aligner is designed to quickly and cost-effectively correct treatment lag up to a four to eight weeks deviation. The hyper elastic rescue aligners could produce movement ranges up to at least 0.5mm per tray.

This retrospective study indicates the potential for further prospective clinical and laboratory studies with improved methods such as 3D superimposition, remote monitoring as well as calibrated inter and intra observer visual inspection methods for better assessment on tracking of each tooth per aligner.
Sub-Concussive Head Impacts From Heading Footballs Do Not Acutely Alter Brain Excitability As Compared to a Control Group
Authors: Hamel R. , Waltzing B. M. , Massey T. , Blenkinsop J. , McConnell L. , Osborne K. , Sesay K. , Stoneman F. , Carter A. , Maaroufi H. , Jenkinson N.
Published: June 2023

Background

Repeated sub-concussive head impacts are a growing brain health concern, but the possible mechanisms of trauma and plausible biomarkers remain elusive. One impediment is the lack of an experimental model to study the effects of sub-concussive head impacts on the brain.

Objectives

This work’s objective was to provide an experimental model to study the acute effects of sub-concussive head impacts on the brain. To do so, this study aimed to replicate previous work from Di Virgilio et al. (2016) showing that head impacts from heading footballs acutely alter brain excitability by increasing corticomotor inhibition.

Methods

Scores from the Rivermead Post-Concussion Questionnaire and measurements of cortical silent period (CSP) duration – obtained using transcranial magnetic stimulation to assess corticomotor inhibition in the central nervous system – were taken before and after participants performed 20 football headings (Headings; n = 30) or control (Control; n = 30).

Results

The results revealed increased headaches and dizziness symptoms in the Headings as compared to the Control group, revealing the qualitative experience of head impacts. The results then revealed that CSP duration similarly lengthened in both the Headings and Control groups, suggesting that head impacts did not cause the increased corticomotor inhibition.

Conclusions

The results show that head impacts from football headings did not acutely alter corticomotor inhibition as compared to a control group that did not experience head impacts, suggesting that excitability changes do not reflect acute sub-concussive brain injuries. Nonetheless, this work suggests that football headings can be used as an experimental model to study the effects of sub-concussive head impacts on brain health. Future work could use the present procedures to investigate additional biomarkers of brain injury.
Accurate identification of structural variations from cancer samples
Authors: Li Le , Hong Chenyang , Xu Jie , Chung Claire Yik-Lok , Leung Alden King-Yung , Boncan Delbert Almerick T. , Cheng Lixin , Lo Kwok-Wai , Lai Paul B. S. , Wong John , Zhou Jingying , Cheng Alfred Sze-Lok , Chan Ting-Fung , Yue Feng , Yip Kevin Y.
Published: June 2023

Structural variations (SVs) are commonly found in cancer genomes. They can cause gene amplification, deletion, and fusion, among other functional consequences. With an average read length of hundreds of kilobases, nano-channel-based optical DNA mapping is powerful in detecting large SVs. However, existing SV calling methods are not tailored for cancer samples, which have special properties such as mixed cell types and sub-clones. Here we propose the COMSV method that is specifically designed for cancer samples. It shows high sensitivity and specificity in benchmark comparisons. Applying to cancer cell lines and patient samples, COMSV identifies hundreds of novel SVs per sample.
Short-term Hebbian learning can implement transformer-like attention
Authors: Ellwood Ian T.
Published: June 2023

Transformers have revolutionized machine learning models of language and vision, but their connection with neuroscience remains tenuous. Built from attention layers, they require a mass comparison of queries and keys that is difficult to perform using traditional neural circuits. Here, we show that neurons can implement attention-like computations using short-term, Hebbian synaptic potentiation. We call our mechanism the match-and-control principle and it proposes that when activity in an axon is synchronous, or matched, with the somatic activity of a neuron that it synapses onto, the synapse can be briefly strongly potentiated, allowing the axon to take over, or control, the activity of the downstream neuron for a short time. In our scheme, the keys and queries are represented as spike trains and comparisons between the two are performed in individual spines allowing for hundreds of key comparisons per query and roughly as many keys and queries as there are neurons in the network.
Active surface flows accelerate the coarsening of lipid membrane domains
Authors: Arnold Daniel P. , Gubbala Aakanksha , Takatori Sho C.
Published: June 2023

Phase separation of multicomponent lipid membranes is characterized by the nucleation and coarsening of circular membrane domains that grow slowly in time as ∼t1/3, following classical theories of coalescence and Ostwald ripening. In this work, we study the coarsening kinetics of phase-separating lipid membranes subjected to nonequilibrium forces and flows transmitted by motor-driven gliding actin filaments. We experimentally observe that the activity-induced surface flows trigger rapid coarsening of non-circular membrane domains that grow as ∼t2/3, a 2× acceleration in the growth exponent compared to passive coalescence and Ostwald ripening. We analyze these results by developing analytical theories based on the Smoluchowski coagulation model and the phase field model to predict the domain growth in the presence of active flows. Our work demonstrates that active matter forces may be used to control the growth and morphology of membrane domains driven out of equilibrium.
Measuring Social Determinants of Health in theAll of UsResearch Program: Technical Document
Authors: Tesfaye Samantha , Cronin Robert , Lopez-Class Maria , Chen Qingxia , Foster Christopher S. , Gu Callie , Guide Andrew , Hiatt Robert A. , Johnson Angelica , Joseph Christine LM , Khatri Parinda , Lim Sokny , Litwin Tamara R. , Munoz Fatima A. , Ramirez Andrea , Sansbury Heather , Schlundt David G. , Viera Emma N. , Dede-Yildirim Elif , Clark Cheryl R.
Published: June 2023

Background

To advance precision medicine and improve population health, theAll of UsResearch Program aims to collect data, including a survey of social determinants of health (SDOH), from over 1 million participants. This report (1) outlines the process used to construct theAll of UsSDOH survey and (2) presents the psychometric characteristics and scoring recommendations for SDOH survey measures.

Methods

A consensus process was used to select a definition of SDOH and conceptual frameworks to develop inclusion and exclusion criteria and priorities for construct consideration. Cognitive interviewing was used to provide an assessment of SDOH survey item performance in English and Spanish.

Scales and scored items were constructed in alignment with validated literature. Item non-response was calculated, and Cronbach ‘s alpha was used to analyze the psychometric properties of each scale, overall and by demographic characteristics. Multivariable logistic regression models were used to examine if demographic categories were associated with item non-response.

Results

Twenty-nine percent (N=117,783) ofAll of Usparticipants submitted SDOH survey data by June 30, 2022. Among those who provided any SDOH survey data, item non-response was infrequent, with most scales having less than 5% incalculable scores due to item non-response. Item non-response varied most along the lines of racial identity, educational attainment, and the language in which the survey was administered (Spanish or English). In our regression models, for most scales, patterns of missing data due to item non-response were seen by racial identity, educational attainment, income level, and age. Internal consistency reliability was greater than 0.80 for almost all scales, with variability by racial identity, educational attainment, and the language of survey administration.

Conclusion

The SDOH survey demonstrated good to excellent reliability across several measures of SDOHs and within multiple population groups that are underrepresented in biomedical research. Bias due to survey non-response and item non-response should be monitored and addressed as the survey is fielded more completely.
Evidence for deliberate burial of the dead byHomo naledi
Authors: Berger Lee R , Makhubela Tebogo , Molopyane Keneiloe , Krüger Ashley , Randolph-Quinney Patrick , Elliott Marina , Peixotto Becca , Fuentes Agustín , Tafforeau Paul , Beyrand Vincent , Dollman Kathleen , Jinnah Zubair , Gillham Angharad Brewer , Broad Kenneth , Brophy Juliet , Chinamatira Gideon , Dirks Paul H. M. , Feuerriegel Elen , Gurtov Alia , Hlophe Nompumelelo , Hunter Lindsay , Hunter Rick , Jakata Kudakwashe , Jaskolski Corey , Morris Hannah , Pryor Ellie , Mpete Maropeng , Roberts Eric , Smilg Jacqueline S. , Tsikoane Mathabela , Tucker Steven , van Rooyen Dirk , Warren Kerryn , Wren Colin D. , Kissel Marc , Spikins Penny , Hawks John
Published: June 2023

In this study we describe new results of excavations in the Dinaledi Subsystem of the Rising Star cave system, South Africa. In two areas within the Hill Antechamber and the Dinaledi Chamber this work uncovered concentrations of abundantHomo naledifossils including articulated, matrix-supported skeletal regions consistent with rapid covering by sediment prior to the decomposition of soft tissue. We additionally re-examine the spatial positioning of skeletal material and associated sediments within the Puzzle Box area, from which abundantH. nalediremains representing a minimum of six individuals were recovered in 2013 and 2014. Multiple lines of evidence exclude the hypothesis that skeletal remains from these three areas come from bodies that decomposed on the floor of the chamber or within a shallow depression prior to burial by sediments. The spatial positioning of skeletal material, the topography of the subsystem, and observations on sediments within and surrounding features exclude the hypothesis that rapid burial by sediment was a result of gravity-driven slumping or spontaneous movement of sediments. We present a minimal hypothesis of hominin cultural burial and test the evidence from all three areas, finding that this hypothesis is most compatible with the pattern of evidence. These results suggest that mortuary behavior including cultural burial was part of the repertoire ofHomo naledi.
Identification of differentially expressed genes and enriched pathways in inflammatory bowel disease using bioinformatics and next generation sequencing data analysis
Authors: Vastrad Basavaraj , Vastrad Chanabasayya
Published: June 2023

Inflammatory bowel disease (IBD) is the most common chronic digestive disorders and inflammation in the gastrointestinal tract globally that is characterized by episodes of abdominal pain, diarrhea, bloody stools and weight loss. However, the pathophysiologic mechanisms of IBD have not been thoroughly investigated. To explore potential targets for treatment of IBD, we reorganized and analyzed next generation sequencing (NGS) dataset (GSE186507). The R package DESeq2 tool was used to screen for differentially expressed genes (DEGs) between IBD and normal control samples. We used the g:Profiler database to perform Gene Ontology (GO) enrichment analysis and the REACTOME for pathway enrichment analysis. Protein-protein interaction (PPI) network construction and module analysis were performed to elucidate molecular mechanisms of DEGs and screen hub genes. Then miRNA-hub gene regulatory network and TF-hub gene regulatory network of these hub genes were visualized by Cytoscape. We also validated the identified hub genes via receiver operating characteristic (ROC) curve analysis. A total of 957 DEGs (478 up regulated genes and 479 down regulated genes) were detected in NGS dataset. And they were mainly enriched in the terms of multicellular organismal process, response to stimulus, GPCR ligand binding and immune system. Based on the data of PPI network, miRNA-hub gene regulatory network and TF-hub gene regulatory network the top hub genes were ranked, including IL7R, ERBB2, SMAD1, RPS26, TLE1, HNF4A, CDKN1A, SRPK1, H3C12 and SFN. In conclusion, the identified DEGs, particularly the hub genes, strengthen the understanding of the development and progression of IDB, and certain novel genes might be used as candidate target molecules to diagnose, monitor and treat IDB.
A guide to computational cotranscriptional folding featuring the SRP RNA
Authors: Badelt Stefan , Lorenz Ronny
Published: June 2023

Although RNA molecules are synthesized via transcription, little is known about the general impact of cotranscriptional folding in vivo. We present different computational approaches for the simulation of changing structure ensembles during transcription, including interpretations with respect to experimental data from literature. Specifically, we analyze different mutations of the E.coli SRP RNA, which has been studied comparatively well in previous literature, yet the details of which specific metastable structures form, as well as when they form are still under debate. Here, we combine thermodynamic and kinetic, deterministic and stochastic models with automated and visual inspection of those systems to derive the most likely scenario of which substructures form at which point during transcription. The simulations do not only provide explanations for present experimental observations, but also suggest previously unnoticed conformations that may be verified through future experimental studies.
A similarity matrix for preserving haplotype diversity among parents in genomic selection
Authors: Musa Abdulraheem A. , Reinsch Norbert
Published: June 2023

Mendelian sampling variability (MSV), determined by the heterozygosity and linkage phases of the parental haplotypes, quantifies the chance of producing offspring with high breeding values. Recent genomic selection criteria combine expected breeding values with MSV to maximize the chance of producing offspring with exceptional breeding values. These criteria, however, tend to select similar parents with high variability potential. Therefore, a measure of haplotype similarity is required to avoid this tendency and preserve diversity. Here, we derive this measure by pairing all potential gametes from two parents based on their segregating marker patterns. Subsequently, a similarity measure between two parents is defined as the absolute value of the covariance between the additive values of the paired gametes on a chromosome. A similarity matrix with absolute covariances as off-diagonal elements and MSVs as diagonal elements summarizes all pairwise similarities between parents. A parent’s similarity to itself equals its MSV. High similarity indicates that the parents share many heterozygous markers with large effects on a trait in the same linkage phase. The concept generalizes to multiple chromosomes, an aggregate genotype with multiple traits, and similarity between zygotes. We demonstrated the properties of the similarity matrix using empirical data. Through simulations, we showed that incorporating the matrix into genomic selection preserves up to 1630% more genetic variability and yields up to 7% more genetic gain relative to index selection in the long term. Although further research is needed, our results show that including similarity matrices preserves haplotype diversity and improves long-term genomic selection.
NINJ1 mediates plasma membrane rupture through formation of nanodisc-like rings
Authors: David Liron , Borges Jazlyn P , Hollingsworth L. Robert , Volchuk Allen , Jansen Isabelle , Steinberg Benjamin E , Wu Hao
Published: June 2023

The membrane proteins Ninjurin1(NINJ1) and Ninjurin2 (NINJ2) are upregulated by nerve injury to increase cell adhesion and promote axonal growth in neurons. NINJ1, but not NINJ2, has also been shown to play an essential role in pyroptosis by promoting plasma membrane rupture downstream of gasdermin D (GSDMD) pore formation, as well as in lytic cell death mediated by other pathways. Recombinant NINJ1 and NINJ2 purified in detergent show irregular rings of various diameters as well as curved filaments. While NINJ1 and NINJ2 both formed ring-like structures when mixed with liposomes, strikingly, only NINJ1, but not NINJ2, ruptures liposome membranes, leading to their dissolution. Because of the better feasibility, we determined the cryo-EM structure of NINJ1 ring segments from detergent by segmenting the irregular rings into shorter fragments. Each NINJ1 subunit contains a transmembrane (TM) helical hairpin (α3 and α4) that likely mediates NINJ1 membrane localization, as well as the side-by-side interaction between adjacent subunits. There are two extracellular domain amphipathic helices (α1 and α2), among which α1 crosses over to the neighboring subunit at the outside facing surface of the ring, to link NINJ1 subunits together into chains. As such, the inner face of the rings is hydrophobic whereas the outer face of the rings is hydrophilic and should repel membranes. Live cell imaging of NINJ1-deficient THP-1 cells reconstituted with NINJ1-eGFP uncovers the pinching off of NINJ1 rings from the cell surface and the loss of NINJ1 to the culture supernatant in oligomerized forms upon inflammasome activation. Formation of rings is also confirmed by super-resolution imaging of endogenous NINJ1 using anti-NINJ1 antibody. These data suggest that membrane insertion of amphipathic helices and formation of rings with a hydrophilic outer surface underlie the mechanism for NINJ1 to pinch off membranes as if it were a nanodisc-forming amphipathic polymer, leading to membrane rupture and lysis during cell death.