bluuebunny/crossref_metadata_2025_split huggingface dataset:
The electronic structure of genome editors from the first principles
Authors: Nierzwicki Łukasz , Ahsan Mohd , Palermo Giulia 
Published: January 2023

Abstract
Ab-initio molecular dynamics enables following the dynamics of biological systems from the first principles, describing the electronic structure and offering the opportunity to “watch” the evolution of biochemical processes with unique resolution, beyond the capabilities of state-of-the-art experimental techniques. This article reports the role of first-principles (ab-initio) molecular dynamics (MD) in the CRISPR-Cas9 genome editing revolution, achieving a profound understanding of the enzymatic function and offering valuable insights for enzyme engineering. We introduce the methodologies and explain the use of ab-initio MD simulations to establish the two-metal dependent mechanism of DNA cleavage in the RuvC domain of the Cas9 enzyme, and how a second catalytic domain, HNH, cleaves the target DNA with the aid of a single metal ion. A detailed description of how ab-initio MD is combined with free-energy methods—i.e., thermodynamic integration and metadynamics—to break and form chemical bonds is given, explaining the use of these methods to determine the chemical landscape and establish the catalytic mechanism in CRISPR-Cas9. The critical role of classical methods is also discussed, explaining theory and application of constant pH MD simulations, used to accurately predict the catalytic residues’ protonation states. Overall, first-principles methods are shown to unravel the electronic structure and reveal the catalytic mechanism of the Cas9 enzyme, providing valuable insights that can serve for the design of genome editing tools with improved catalytic efficiency or controllable activity.
Vulnerability of California roadways to post-wildfire debris flows
Authors: Li Rui , Chester Mikhail V 
Published: January 2023

Abstract
Post-wildfire debris flows represent a significant hazard for transportation infrastructure. The location and intensity of post-fire debris movements are difficult to predict, and threats can persist for several years until the watershed is restored to pre-fire conditions. This situation might worsen as climate change forecasts predict increasing numbers of wildfire burned areas and extreme precipitation intensity. New insights are needed to improve understanding of how roadways are vulnerable to post-fire flows and how to prioritize protective efforts. Using California as a case study, the vulnerability of transportation infrastructure to post-fire debris flow was assessed considering geologic conditions, vegetation conditions, precipitation, fire risk, and roadway importance under current and future climate scenarios. The results showed significant but uneven statewide increases in the number of vulnerable roadways from the present to future emission scenarios. Under current climate conditions, 0.97% of roadways are highly vulnerable. In the future, the ratio of vulnerable roadways is expected to increase 1.9–2.3 times in the representative concentration pathways (RCPs) 4.5 emission scenarios, and 3.5–4.2 times in the RCP 8.5 emission scenarios. The threat of post-fire debris flow varies across the state, as precipitation changes are uneven. The vulnerability assessment is positioned to (a) identify, reinforce, and fortify highly vulnerable roadways, (b) prioritize watershed fire mitigation, and (c) guide future infrastructure site selection.
Isolated subcutaneous implantable cardioverter-defibrillator generator displacement causing inappropriate shocks despite preserved lead tip and coil position: a case report
Authors: Chow Ji-Jian , Bilham James , Lane Rebecca 
Published: January 2023

AbstractBackgroundSubcutaneous implantable cardioverter-defibrillators (S-ICDs) are increasingly used in patients without a pacing indication, and may reduce venous complications, endocarditis and extraction morbidity. Subcutaneous implantable cardioverter-defibrillator displacements may be less obvious than their transvenous counterparts.Case summaryA 59-year-old man was found to have dilated cardiomyopathy associated with heavy alcohol intake following investigation for a stroke. Despite 2 years of alcohol cessation and optimal drug therapy, his ejection fraction remained severely impaired, and he received an S-ICD using the manufacturer recommended screening and implant method, and by an experienced operator. Ten months later, inappropriate shocks were delivered despite optimal programming. Device displacement was demonstrated by lateral chest radiography on the second instance of inappropriate therapy. On the first admission, a lateral film was not performed, and simple device programming was undertaken which failed to prevent the second occurrence. The patient requested an explant; as ventricular function had improved following initiation of sacubutril/valsartan, the clinical team opted to remove the device.DiscussionCareful inspection of lateral chest films and review of device indication are needed to reduce the risk of inappropriate shocks. This is the first description of inappropriate device activity following lone generator displacement—lead displacement is well described.
Case report: human granulocytic anaplasmosis causes acute myopericarditis with atrial fibrillation
Authors: Levy Alexander M , Martin Lila M , Krakower Douglas S , Grandin E Wilson 
Published: January 2023

Abstract

Background
Tick-borne illness are becoming increasingly common, in a spreading geographic area. Lyme disease is a well-known cause of cardiovascular disease, but anaplasmosis has previously had relatively little reported association with conduction and myocardial disease.

Case Summary
A 65-year-old man with fever and malaise was admitted to the intensive care unit in shock. Electrocardiogram showed new atrial fibrillation and conduction abnormalities. Transthoracic echocardiogram demonstrated normal left ventricular ejection fraction but significant right ventricle dysfunction. Cardiac magnetic resonance imaging findings were consistent with myopericarditis. Workup revealed human granulocytic anaplasmosis without Lyme. He recovered with doxycycline.

Conclusion
To our knowledge, this is one of the first reported cases of anaplasmosis causing electrical conduction and myocardial disease with haemodynamic instability in an isolated infection. Treatment with appropriate antibiotics and supportive care allowed the patient to recover to his functional baseline within a month from being discharged from the hospital. Recognition of anaplasmosis in the absence of Lyme disease as a potential cause of electrical and myocardial disease is important in the context of increasing anaplasmosis incidence across the United States.
Management of life-threatening deformation of obstructive transcatheter mitral valve replacement bioprosthesis with balloon inflation in left ventricular outflow tract: a case report
Authors: Cavalerie Hugo , Casassus Frederic , Dubourg Benjamin , Darremont Olivier 
Published: January 2023

Abstract

Background
Left ventricular outflow track (LVOT) obstruction (LVOTO) is a severe complication of transcatheter mitral valve replacement (TMVR) procedures, with an uncertain prognosis and only few strategies available to prevent its occurrence. TMVR is thus contraindicated in some patients because of a high risk of LVOTO onset. We demonstrate how LVOTO can be managed with a balloon inflation in the LVOT and a D-shaped deformation of the bioprosthetic valve.

Case summary
A 64-year-old female presented with acute pulmonary oedema 2 weeks following aortic valve replacement and aorto-coronary bypass surgeries. A concomitant mitral stenosis, secondary to significant calcifications of the mitral annulus, was not treated during the procedure. After surgery, the mitral valvulopathy caused an acute heart failure and TMVR was performed by the heart team. The procedure was complicated by a cardiac arrest secondary to the onset of LVOTO which was managed by a balloon inflation in the LVOT and an alcohol septal ablation. Two-year follow-up shows a favourable outcome of the patient and good function of the prosthetic valve despite its deformation.

Discussion
This case highlights the successful management of a LVOTO following valve-in-mitral annular calcification TMVR by balloon inflation in the LVOT. It is strongly recommended to place a ‘rescue’ guidewire in transaortic position during TMVR in order to manage the potential onset of acute LVOTO.
The Unified Patent Court’s Opt-Out Option – A General Introduction
Authors: Luginbuehl Stefan , Kotzur Juliane 
Published: January 2023

Abstract
With the entry into force of the Agreement on a Unified Patent Court (UPCA) on 1 June 2023, a common patent court will be created for 17 Member States of the European Union. It will be competent for disputes concerning the infringement and revocation of Unitary Patents and classic European patents. At the request of the users, a so-called opt-out mechanism was introduced, which allows the jurisdiction of the Court to be excluded by a corresponding notification. Such opt-outs can be filed via the Court’s case management system as of the start of the ‘sunrise period’ on 1 March 2023. This article provides a first general practical overview concerning the recording of such notifications.***
The Road from Geneva
Authors: Winter Jay 
Published: January 2023

Abstract
This chapter charts the emergence of a central part of the Treaty of Lausanne of 1923—the compulsory population exchange agreement introduced initially by the League of Nations High Commissioner for Refugees, Fridtjof Nansen on 20 November 1922, and agreed on 30 January 1923 by Greek and Turkish delegates. In the past the end of wars was marked by an exchange of prisoners. This was the first time in history that a compulsory exchange of civilians became a precondition for peace. This measure is placed in the framework of the work of the League of Nations to save the lives of refugees and to prevent the spread of endemic and epidemic disease. The price paid for this agreement was the legalization of ethnic cleansing on a massive scale. Here was the moment when the civilianization of war arrived as an indelible part of the fabric of international affairs.
Introduction
Authors: Steinglass Steven H. , Scarselli Gino J. 
Published: January 2023

Abstract
This book begins with a detailed essay on the history of the Ohio Constitution, including the prestatehood Ordinance of 1787 (i.e., the Northwest Ordinance), the adoption of the 1802 Constitution, which resulted in Ohio’s admission as the seventeenth state in the union, and the adoption of the 1851 Constitution, Ohio’s current constitution. Detailed attention is given to the thirty-four amendments that have their origins in the work of the Progressive-era 1912 Constitutional Convention; this includes the initiative and referendum and the home rule amendment. The essay also covers the modern efforts to use commissions to revise the constitution, stare decisis, judicial selection, and the emergence of the new judicial federalism in Ohio.
Special Report: The Moore Pediatric Surgery Center: An Evolving Model for Pediatric Orthopaedic Surgical Care in a Limited Resource Environment
Authors: Taylor Zachary R. , Hamblin Robert W. , Shaw Brian A. , Navas-Solares Juan C. , Shaw Lisa F. 
Published: January 2023

Abstract:
The authors describe their 11-year experience with 1 model for providing short-term (about 1 wk/y in country) pediatric orthopaedic surgical care in a limited resource environment. This paper provides a detailed narrative of 1 team’s pediatric orthopaedic work at the Moore Pediatric Surgery Center in Guatemala City, how it has evolved over these 11 years, financial aspects of the model, and examines patient follow-up data for a consecutive 8-year period. The authors have reviewed financial records, case lists, patient charts from 2014 to 2022, and patient photographic records from The Moore Center and as provided via internet by a local contracted Guatemalan pediatric orthopaedic fellowship-trained surgeon to present a complete picture of how the service functions. Specific follow-up data included: last follow-up date, date discharged from follow-up, and major complications including infection, surgical wound dehiscence, return for unplanned surgery, major nerve injury, and recurrent hip dislocation for cases of closed or open reduction of developmental hip dislocation. A total of 297 consecutive pediatric orthopaedic surgical patients were identified from 2014 to 2022. Of these, charts were found for 235 patients (135 female, 110 male), of which 43% were from the urban Guatemala City region. Two hundred sixteen (72%) had at least 1 follow-up clinic visit, and 87 (37%) had at least 1-year follow-up or were discharged. All complications identified by this retrospective chart review included 4 recurrent hip dislocations (3 after closed reduction), 1 femur fracture after implant removal, 1 superficial infection requiring antibiotics, 1 partial dehiscence treated only with dressings, 1 thumb subluxation, and 1 failed graft with internal fixation for congenital pseudoarthrosis of tibia.

Conclusions:
The Moore Pediatric Surgery Center is a financially viable, sustainable, safe, and effective model for delivering short-term surgical care for many pediatric orthopaedic conditions in a limited resource environment.

Level of Evidence:
None (descriptive).
Impact of Objective Colonic and Whole Gut Motility Data as Measured by Wireless Motility Capsule on Outcomes of Antireflux Surgery
Authors: Eriksson Sven E , Maurer Nicole , Zheng Ping , Sarici Inanc S , DeWitt Ann , Riccardi Margaret , Jobe Blair A , Ayazi Shahin 
Published: January 2023

BACKGROUND:
Studies show higher rates of dissatisfaction with antireflux surgery (ARS) outcomes in patients with chronic constipation. This suggests a relationship between colonic dysmotility and suboptimal surgical outcome. However, due to limitations in technology, there is no objective data available examining this relationship. The wireless motility capsule (WMC) is a novel technology consisting of an ingestible capsule equipped with pH, temperature, and pressure sensors, which provide information regarding regional and whole gut transit times, pH and motility. The aim of this study was to assess the impact of objective regional and whole gut motility data on the outcomes of ARS.

STUDY DESIGN:
This was a retrospective review of patients who underwent WMC testing before ARS. Transit times, motility, and pH data obtained from different gastrointestinal tract regions were used in analysis to determine factors that impact surgical outcome. A favorable outcome was defined as complete resolution of the predominant reflux symptom and freedom from antisecretory medications.

RESULTS:
The final study population consisted of 48 patients (fundoplication [n = 29] and magnetic sphincter augmentation [n = 19]). Of those patients, 87.5% were females and the mean age ± SD was 51.8 ± 14.5 years. At follow-up (mean ± SD, 16.8 ± 13.2 months), 87.5% of all patients achieved favorable outcomes. Patients with unfavorable outcomes had longer mean whole gut transit times (92.0 hours vs 55.7 hours; p = 0.024) and colonic transit times (78.6 hours vs 47.3 hours; p = 0.028), higher mean peak colonic pH (8.8 vs 8.15; p = 0.009), and higher mean antral motility indexes (310 vs 90.1; p = 0.050).

CONCLUSIONs:
This is the first study to demonstrate that objective colonic dysmotility leads to suboptimal outcomes after ARS. WMC testing can assist with preoperative risk assessment and counseling for patients seeking ARS.
Perioperative and Disease-Free Survival Outcomes after Hepatectomy for Centrally Located Hepatocellular Carcinoma Guided by Augmented Reality and Indocyanine Green Fluorescence Imaging: A Single-Center Experience
Authors: Zhu Wen , Zeng Xiaojun , Hu Haoyu , Xiang Nan , Zeng Ning , Wen Sai , Tian Jie , Yang Jian , Fang Chihua 
Published: January 2023

BACKGROUND:
Laparoscopic hepatectomy for centrally located hepatocellular carcinoma is challenging to perform. Augmented reality navigation (ARN) and fluorescence imaging are currently safe and reproducible techniques for hepatectomy, but the efficacy results for centrally located hepatocellular carcinoma have not been reported. This study aimed to evaluate the efficacy of an ARN system combined with fluorescence imaging (ARN-FI) in laparoscopic hepatectomy for centrally located hepatocellular carcinoma.

STUDY DESIGN:
This was a post hoc analysis of an original nonrandomized clinical trial that was designed to evaluate the feasibility and efficacy of ARN-FI for laparoscopic liver resection. A total of 76 patients were consecutively enrolled from June 2018 to June 2021, of which 42 underwent laparoscopic hepatectomy using ARN-FI (ARN-FI group), and the other 34 who did not use ARN-FI guidance (non–ARN-FI group). Perioperative outcomes and disease-free survival were compared between the 2 groups.

RESULTS:
Compared with the non–ARN-FI group, the ARN-FI group had less intraoperative blood loss (median 275 vs 300 mL, p = 0.013), lower intraoperative transfusion rate (14.3% vs 64.7%, p < 0.01), shorter postoperative hospital stay (median 8 vs 9 days, p = 0.005), and lower postoperative complication rate (35.7% vs 61.8%, p = 0.024). There was no death in the perioperative period and follow-up period. There was no significant difference in overall disease-free survival between the 2 groups (p = 0.16).

CONCLUSIONs:
The ARN system and fluorescence imaging may be of value in improving the success rate of surgery, reducing postoperative complications, accelerating postoperative recovery, and shortening postoperative hospital stay.
Cell Segmentation in Images Without Structural Fluorescent Labels
Authors: Zyss Daniel , Ribeiro Susana A. , Ludlam Mary J.C. , Walter Thomas , Fehri Amin 
Published: January 2023

AbstractHigh-content screening (HCS) provides an excellent tool to understand the mechanism of action of drugs on disease-relevant model systems. Careful selection of fluorescent labels (FLs) is crucial for successful HCS assay development. HCS assays typically comprise (1) FLs containing biological information of interest, and (2) additional structural FLs enabling instance segmentation for downstream analysis. However, the limited number of available fluorescence microscopy imaging channels restricts the degree to which these FLs can be experimentally multiplexed. In this paper, we present a segmentation workflow that overcomes the dependency on structural FLs for image segmentation, typically freeing 2 fluorescence microscopy channels for biologically relevant FLs. It consists in extracting structural information encoded within readouts that are primarily biological, by fine-tuning pre-trained state-of-the-art generalist cell segmentation models for different combinations of individual FLs, and aggregating the respective segmentation results together. Using annotated datasets that we provide, we confirm our methodology offers improvements in performance and robustness across several segmentation aggregation strategies and image acquisition methods, over different cell lines and various FLs. It thus enables the biological information content of HCS assays to be maximized without compromising the robustness and accuracy of computational single-cell profiling.Impact StatementThis methodological paper describes a framework enabling cell segmentation for datasets without structural fluorescent labels to highlight cell organelles. Such capabilities favorably impact costs and possible discoveries in single-cell downstream analysis by improving our ability to incorporate more biological read-outs into a single assay. The perspective of computational and experimental biologist coauthors ensures a multidisciplinary viewpoint and accessibility for a wide readership.
Non-senescent species are not immortal: stress and decline in two planaria species
Authors: Deere Jacques A. , Holland Penelope , Aboobaker Aziz , Salguero-Gomez Roberto 
Published: January 2023

ABSTRACT1. Potential immortality is observed in several species (e.g., prickly pear cactus, hydra, flatworms) and is indicative of their negligible or even negative senescence rates. Unlike in senescent species, which experience reduced individual performance with age due to physiological degradation, species with negligible or negative senescence display mortality rates that remain constant or decline with age, respectively. These rates vary across taxa and are correlated with life history traits. Yet, the extent to which variable resource availability, a key driver of variation in life history traits, impacts species that show negligible or negative senescence is currently unknown.2. Here, we examine whether and how variation in the quantity, quality, and feeding interval of resources impact population structure, population performance, and life history trait trade-offs in two long-lived planaria that do not senesce:Schmidtea mediterraneaandDugesia tahitiensis. In a full factorial design, different combinations of resource quantity (reduced intake, standard intake and high intake) and quality (high and low quality) were provided in two different feeding intervals (7-day and 14-day intervals) for 19 weeks.3. We show that variability in resource availability, via decreases in quantity, quality, and frequency of resources, does not diminish population viability in either species but does result in suboptimal conditions of stress inS. mediterranea.4. The high population viability we report can be attributed to two different mechanisms: increased reproduction or increased investment into maintenance at the expense of reproduction. Moreover, which mechanism was responsible for said high population viability was context-dependent and modulated by the specific life history strategy of the two planaria species.5. We show that suboptimal conditions can cause stress responses that have significant impacts on non-senescent species. The context-dependent response we observe suggests that species that do not senesce but are subject to suboptimal conditions of stress may ultimately exhibit declines in performance and ultimately die. A clearer understanding of the impact of suboptimal conditions of resource availability on non-senescent species is needed to determine the extent of stress experienced and ultimately whether a species can truly be immortal.
A novel supplemental circadian feedback loop in CA1 mediates mood-related behaviors
Authors: Wang Xin-Ling 
Published: January 2023

AbstractTraditional circadian clock feedback loops include positive branches and negative branches.Pergenes belong to the negative branches. There are three subtypes ofPergenes namedPer1, Per2andPer3. The relationship among these subtypes has been rarely reported. In this study, we aimed to explore the action betweenPer1andPer2genes, which are known to be critical in the pathogenesis of mood disorder. We revealed thatPer1has a positive action on the expression ofPer2, whilePer2shows a negative effect onPer1expression. This forms a novel feedback loop. Besides, both knockdown and over-expression ofPer1exhibit a pro-depressive effect, indicating a potential mediation in the pathogenesis of major depressive disorder. Correspondingly, knockdown ofPer2induces mania-like behavior, while, over-expression ofPer2produces a pro-depressive effect, suggesting its involvement in the pathophysiology of bipolar disorder. This research may provide an advance in the differential diagnosis between the two diseases in the future.HighlightsPer1promotes the expression ofPer2, whilePer2inhibit the expression ofPer1in CA1, forming a negative feedback loop.Both knockdown and over-expression ofPer1in CA1 induce depression-like behaviors, whilePer2involves in both mania and depression-like behaviors.