bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences between κ and λ light chain amyloidosis analyzed by a pathologic scoring system
Authors: Wu Huijuan , L’Imperio Vincenzo , Rossi Mattia , Kapp Meghan E , Paueksakon Paisit
Published: March 2023

Objectives

Amyloid light chain (AL)-κ and AL-λ share common histopathologic changes; however, the potential difference in clinical manifestations, histologic findings, and clinical significance between the 2 subtypes remain unclear.

Methods

In a retrospective study, 94 kidney biopsies for AL amyloidosis were evaluated using the composite scarring injury score (CSIS) and amyloid score (AS). Results were then compared between AL-κ and AL-λ.

Results

Comparing AS and CSIS between AL-κ and AL-λ, the AS was significantly higher in AL-κ than in AL-λ, with 2 components of AS (capillary wall and vascular amyloid) scoring higher in AL-κ than in AL-λ, while mesangial and interstitial ASs were similar in the 2 cohorts. In addition, the proportion of periodic acid–Schiff strong-staining amyloid in AL-κ was markedly higher than in AL-λ. There was no significant difference in CSIS and its components between the 2 subtypes of AL amyloidosis.

Conclusions

Overall, AL-κ presents with higher serum creatinine and a higher AS score than AL-λ at biopsy, which may indicate a worse prognosis and be an important reference for clinical management.
The Board-Room Where It Happens—A Research Note
Authors: Listokin Yair
Published: March 2023

Activist investors often run “short-slate” proxy contests, seeking representation short of a majority on a corporation’s board of directors. Do activists pursue short-slate representation because they want to be an instrumental part of a corporation’s governance, or because success in a short-slate contest sends a signal to incumbent management to reform, lest there be a future proxy contest for control of the corporation? Event study evidence from “the largest proxy battle ever” suggests that a single board seat is instrumentally valuable, exclusive of signaling effects. In 2017, activist hedge fund Trian Management vied with the management of Procter & Gamble (P&G) over a single seat on P&G’s board of directors. In a razor-thin contest, first P&G and then Trian was declared the winner. P&G’s market value rose significantly on news raising the likelihood of Trian representation on the board and fell significantly with news favoring P&G incumbent management. Since the identity of the winner had important implications for the P&G board’s composition but added almost no signal about Trian’s ability to gain control of P&G in the future, these results offer evidence that minority board representation directly yields value for activists.
Defining diagnostic uncertainty as a discourse type: A transdisciplinary approach to analysing clinical narratives of Electronic Health Records
Authors: Nickels Lindsay C , Marshall Trisha L , Edgerton Ezra , Brady Patrick W , Hagedorn Philip A , Lee James J
Published: March 2023

Diagnostic uncertainty is prevalent throughout medicine and significantly impacts patient care, especially when it goes unrecognized. However, we lack a reliable clinical means of identifying uncertainty. This study evaluates the narrative discourse within clinical notes in the Electronic Health Record as a means of identifying diagnostic uncertainty. Recognizing that discourse producers use language ‘semi-automatically’ (Partington et al. 2013), we hypothesized that clinicians include distinct indications of uncertainty in their written assessments, which could be elucidated by linguistic analysis. Using a cohort of patients prospectively identified as having an uncertain diagnosis (UD), we conducted a detailed corpus-assisted discourse analysis. The analysis revealed a set of linguistic indicators constitutive of diagnostic uncertainty including terms of modality, register-specific terms, and linguistically identifiable clinical behaviours. This dictionary of UD indicators was thoroughly tested, and its performance was compared with a matched-control dataset. Based on the findings, we built a machine learning classification algorithm with the ability to predict UD patient cohorts with 87.0% accuracy, effectively demonstrating the feasibility of using clinical discourse to classify patients and directly impact the clinical environment.
Multi-task adaptive pooling enabled synergetic learning of RNA modification across tissue, type and species from low-resolution epitranscriptomes
Authors: Song Yiyou , Wang Yue , Wang Xuan , Huang Daiyun , Nguyen Anh , Meng Jia
Published: March 2023

Post- and co-transcriptional RNA modifications are found to play various roles in regulating essential biological processes at all stages of RNA life. Precise identification of RNA modification sites is thus crucial for understanding the related molecular functions and specific regulatory circuitry. To date, a number of computational approaches have been developed for in silico identification of RNA modification sites; however, most of them require learning from base-resolution epitranscriptome datasets, which are generally scarce and available only for a limited number of experimental conditions, and predict only a single modification, even though there are multiple inter-related RNA modification types available. In this study, we proposed AdaptRM, a multi-task computational method for synergetic learning of multi-tissue, type and species RNA modifications from both high- and low-resolution epitranscriptome datasets. By taking advantage of adaptive pooling and multi-task learning, the newly proposed AdaptRM approach outperformed the state-of-the-art computational models (WeakRM and TS-m6A-DL) and two other deep-learning architectures based on Transformer and ConvMixer in three different case studies for both high-resolution and low-resolution prediction tasks, demonstrating its effectiveness and generalization ability. In addition, by interpreting the learned models, we unveiled for the first time the potential association between different tissues in terms of epitranscriptome sequence patterns. AdaptRM is available as a user-friendly web server from http://www.rnamd.org/AdaptRM together with all the codes and data used in this project.
Effective and efficient active learning for deep learning-based tissue image analysis
Authors: Meirelles André L S , Kurc Tahsin , Kong Jun , Ferreira Renato , Saltz Joel , Teodoro George
Published: March 2023

Motivation

Deep learning attained excellent results in digital pathology recently. A challenge with its use is that high quality, representative training datasets are required to build robust models. Data annotation in the domain is labor intensive and demands substantial time commitment from expert pathologists. Active learning (AL) is a strategy to minimize annotation. The goal is to select samples from the pool of unlabeled data for annotation that improves model accuracy. However, AL is a very compute demanding approach. The benefits for model learning may vary according to the strategy used, and it may be hard for a domain specialist to fine tune the solution without an integrated interface.

Results

We developed a framework that includes a friendly user interface along with run-time optimizations to reduce annotation and execution time in AL in digital pathology. Our solution implements several AL strategies along with our diversity-aware data acquisition (DADA) acquisition function, which enforces data diversity to improve the prediction performance of a model. In this work, we employed a model simplification strategy [Network Auto-Reduction (NAR)] that significantly improves AL execution time when coupled with DADA. NAR produces less compute demanding models, which replace the target models during the AL process to reduce processing demands. An evaluation with a tumor-infiltrating lymphocytes classification application shows that: (i) DADA attains superior performance compared to state-of-the-art AL strategies for different convolutional neural networks (CNNs), (ii) NAR improves the AL execution time by up to 4.3×, and (iii) target models trained with patches/data selected by the NAR reduced versions achieve similar or superior classification quality to using target CNNs for data selection.

Availability and implementation

Source code: https://github.com/alsmeirelles/DADA.
Modeling the impact of the Omicron infection wave in Germany
Authors: Maier Benjamin F , Burdinski Angelique , Wiedermann Marc , Rose Annika H , Schlosser Frank , an der Heiden Matthias , Wichmann Ole , Harder Thomas , Brockmann Dirk
Published: March 2023

In November 2021, the first infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern (VOC) B.1.1.529 (‘Omicron’) was reported in Germany, alongside global reports of reduced vaccine efficacy (VE) against infections with this variant. The potential threat posed by its rapid spread in Germany was, at the time, difficult to predict. We developed a variant-dependent population-averaged susceptible-exposed-infected-recovered infectious-disease model that included information about variant-specific and waning VEs based on empirical data available at the time. Compared to other approaches, our method aimed for minimal structural and computational complexity and therefore enabled us to respond to changes in the situation in a more agile manner while still being able to analyze the potential influence of (non-)pharmaceutical interventions (NPIs) on the emerging crisis. Thus, the model allowed us to estimate potential courses of upcoming infection waves in Germany, focusing on the corresponding burden on intensive care units (ICUs), the efficacy of contact reduction strategies, and the success of the booster vaccine rollout campaign. We expected a large cumulative number of infections with the VOC Omicron in Germany with ICU occupancy likely remaining below capacity, nevertheless, even without additional NPIs. The projected figures were in line with the actual Omicron waves that were subsequently observed in Germany with respective peaks occurring in mid-February and mid-March. Most surprisingly, our model showed that early, strict, and short contact reductions could have led to a strong ‘rebound’ effect with high incidences after the end of the respective NPIs, despite a potentially successful booster campaign. The results presented here informed legislation in Germany. The methodology developed in this study might be used to estimate the impact of future waves of COVID-19 or other infectious diseases.
Effect of different quilting techniques on seroma formation after breast surgery: retrospective study
Authors: van Zeelst Lotte J , van der Waal Dagmar C , Keemers-Gels Mariël E , van den Wildenberg Frits J H , Schlooz-Vries Margrethe S , Wijers Charlotte H W , de Wilt Johannes H W , Strobbe Luc J A
Published: March 2023

Background

Quilting, a technique in which skin flaps are sutured to the underlying muscle, reduces seroma after mastectomy and/or axillary lymph node dissection. The aim of this study was to assess the effect of different quilting techniques on the formation of clinically significant seroma.

Methods

This was a retrospective study including patients undergoing mastectomy and/or axillary lymph node dissection. Four breast surgeons applied the quilting technique based on their own discretion. Technique 1 was performed using Stratafix in 5–7 rows placed at 2–3 cm distance. Technique 2 was performed using Vicryl 2–0 in 4–8 rows placed at 1.5–2 cm distance. Technique 3 was performed using Vicryl 0/1 in 3 rows placed at 3–4 cm distance. Technique 4 was performed using Vicryl 0 in 4–5 rows placed at 1.5 cm distance. The primary outcome was clinically significant seroma.

Results

A total of 445 patients were included. Clinically significant seroma incidence was 4.1 per cent (six of 147) for technique 1, which was significantly lower than that for the other techniques (25.0 per cent (29 of 116), 29.4 per cent (32 of 109), and 33 per cent (24 of 73) for techniques 2, 3, and 4 (P < 0.001) respectively). The duration of surgery was not significantly longer for technique 1 compared with the other three techniques. The length of hospital stay, number of additional visits to the outpatient clinic, and reoperations did not differ significantly between the four techniques.

Conclusion

Quilting using Stratafix and placing 5–7 rows with 2–3 cm distance between the stitches associates with low clinically significant seroma incidence without adverse effects.
Thalamocortical disconnection involved in pusher syndrome
Authors: Rosenzopf Hannah , Klingbeil Julian , Wawrzyniak Max , Röhrig Lisa , Sperber Christoph , Saur Dorothee , Karnath Hans-Otto
Published: March 2023

The presence of both isolated thalamic and isolated cortical lesions have been reported in the context of pusher syndrome—a disorder characterized by a disturbed perception of one’s own upright body posture, following unilateral left- or right-sided stroke. In recent times, indirect quantification of functional and structural disconnection increases the knowledge derived from focal brain lesions by inferring subsequent brain network damage from the respective lesion. We applied both measures to a sample of 124 stroke patients to investigate brain disconnection in pusher syndrome. Our results suggest a hub-like function of the posterior and lateral portions of the thalamus in the perception of one’s own postural upright. Lesion network symptom mapping investigating functional disconnection indicated cortical diaschisis in cerebellar, frontal, parietal and temporal areas in patients with thalamic lesions suffering from pusher syndrome, but there was no evidence for functional diaschisis in pusher patients with cortical stroke and no evidence for the convergence of thalamic and cortical lesions onto a common functional network. Structural disconnection mapping identified posterior thalamic disconnection to temporal, pre-, post- and paracentral regions. Fibre tracking between the thalamic and cortical pusher lesion hotspots indicated that in cortical lesions of patients with pusher syndrome, it is disconnectivity to the posterior thalamus caused by accompanying white matter damage, rather than the direct cortical lesions themselves, that lead to the emergence of pusher syndrome. Our analyses thus offer the first evidence for a direct thalamo-cortical (or cortico-thalamic) interconnection and, more importantly, shed light on the location of the respective thalamo-cortical disconnections. Pusher syndrome seems to be a consequence of direct damage or of disconnection of the posterior thalamus.
Preclinical Alzheimer’s disease: how to predict who will decline next year?
Authors: Hanseeuw Bernard J , Johnson Keith A
Published: March 2023

This scientific commentary refers to ‘Medial temporal tau predicts memory decline in cognitively unimpaired elderly’, by Kwan et al. (https://doi.org/10.1093/braincomms/fcac325).
Exosome-transmitted miR-29a induces colorectal cancer metastasis by destroying the vascular endothelial barrier
Authors: Liu Keshu , Dou Rongzhang , Yang Chaogang , Di Ziyang , Shi Dongdong , Zhang Chunxiao , Song Jialin , Fang Yan , Huang Sihao , Xiang Zhenxian , Zhang Weisong , Wang Shuyi , Xiong Bin
Published: March 2023

Metastasis is the leading cause of colorectal cancer treatment failure and mortality. Communication between endothelium and tumor cells in the tumor microenvironment is required for cancer metastasis. Tumor-derived exosomes have been shown to increase vascular permeability by delivering microRNA (miRNA) to vascular endothelial cells, facilitating cancer metastasis. The mechanism by which Epithelial-mesenchymal transition (EMT) tumor cell-derived exosomes influence vascular permeability remains unknown. MicroRNA-29a (miR-29a) expression is up-regulated in colorectal cancer (CRC) tissues, which is clinically significant in metastasis. Exosomal miR-29a secreted by EMT-CRC cells has been found to decrease the expression of Zonula occlusion 1 (ZO-1), Claudin-5, and Occludin via targeting Kruppel-like factor 4 (KLF4). In vitro co-culture investigations further revealed that EMT-cancer cells release exosomal miR-29a, which alters vascular endothelial permeability. Furthermore, exosomal miR-29a promoted liver metastases in CRC mice. Our findings demonstrate that EMT-CRC cells may transport exosomal miR-29a to endothelial cells in the tumor microenvironment (TME). As a result, increased vascular permeability promotes the development and metastasis of CRC. Exosomal miR-29a has the potential to be a predictive marker for tumor metastasis as well as a viable therapeutic target for CRC.
Call for a standardized environmental sustainability checklist for reporting clinical research
Authors: Edache Enenche , Seeley Becky , Johnson-Ogbuneke James , Hailston Luke , Moiz Haseeb , Madhwapathi Vidya , Tso Simon
Published: March 2023

This article calls for a standardized environmental sustainability checklist for routine reporting of clinical research.
Overfull: Too Large Aggregate Signatures Based on Lattices
Authors: Boudgoust Katharina , Roux-Langlois Adeline
Published: March 2023

The Fiat-Shamir with Aborts paradigm of Lyubashevsky has given rise to efficient lattice-based signature schemes. One popular implementation is Dilithium, which has been selected for standardization by the US National Institute of Standards and Technology (NIST). Informally, it can be seen as a lattice analog of the well-known discrete-logarithm-based Schnorr signature. An interesting research question is whether it is possible to combine several unrelated signatures, issued from different signing parties on different messages, into one single aggregated signature. Of course, its size should be significantly smaller than the trivial concatenation of all signatures. Ideally, the aggregation can be done offline by a third party, called public aggregation. Previous works have shown that it is possible to half-aggregate Schnorr signatures, but it was left open if the underlying techniques can be adapted to the lattice setting. In this work, we show that, indeed, we can use similar strategies to obtain a signature scheme allowing for public aggregation whose hardness is proven assuming the intractability of well-studied problems on module lattices. Unfortunately, our scheme produces aggregated signatures that are larger than the trivial solution of concatenating. This is due to peculiarities that seem inherent to lattice-based cryptography. Its motivation is thus mainly pedagogical.
Impact of frailty on the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation: a nationwide cohort study
Authors: Grymonprez Maxim , Petrovic Mirko , De Backer Tine L , Steurbaut Stephane , Lahousse Lies
Published: March 2023

Aims

Data on non-vitamin K antagonist oral anticoagulants (NOACs) use in patients with atrial fibrillation (AF) and frailty are scarce. Therefore, the impact of frailty on AF-related outcomes and benefit–risk profiles of NOACs in patients with frailty were investigated.

Methods and results

AF patients initiating anticoagulation between 2013 and 2019 were included using Belgian nationwide data. Frailty was assessed with the Claims-based Frailty Indicator. Among 254 478 anticoagulated AF patients, 71 638 (28.2%) had frailty. Frailty was associated with higher all-cause mortality risks [adjusted hazard ratio (aHR) 1.48, 95% confidence interval (CI) (1.43–1.54)], but not with thromboembolism or bleeding. Among subjects with frailty (78 080 person-years of follow-up), NOACs were associated with lower risks of stroke or systemic embolism (stroke/SE) [aHR 0.77, 95%CI (0.70–0.86)], all-cause mortality [aHR 0.88, 95%CI (0.84–0.92)], and intracranial bleeding [aHR 0.78, 95%CI (0.66–0.91)], a similar major bleeding risk [aHR 1.01, 95%CI (0.93–1.09)], and higher gastrointestinal bleeding risk [aHR 1.19, 95%CI (1.06–1.33)] compared with VKAs. Major bleeding risks were lower with apixaban [aHR 0.84, 95%CI (0.76–0.93)], similar with edoxaban [aHR 0.91, 95%CI (0.73–1.14)], and higher with dabigatran [aHR 1.16, 95%CI (1.03–1.30)] and rivaroxaban [aHR 1.11, 95%CI (1.02–1.21)] compared with VKAs. Apixaban was associated with lower major bleeding risks compared with dabigatran [aHR 0.72, 95%CI (0.65–0.80)], rivaroxaban [aHR 0.78, 95%CI (0.72–0.84)] and edoxaban [aHR 0.74, 95%CI (0.65–0.84)], but mortality risk was higher compared with dabigatran and edoxaban.

Conclusion

Frailty was an independent risk factor of death. Non-vitamin K antagonist oral anticoagulants had better benefit–risk profiles than VKAs in patients with frailty, especially apixaban, followed by edoxaban.
Left atrial function and not volume predicts mid-to-late atrial fibrillation after mitral valve repair
Authors: van Kampen Antonia , Nagata Yasufumi , Huang Alex Lin-I , Mohan Navyatha , Dal-Bianco Jacob P , Hung Judy W , Borger Michael A , Levine Robert A , Sundt Thoralf M , Melnitchouk Serguei
Published: March 2023

OBJECTIVES

Patients undergoing surgical mitral valve repair (MVr) for degenerative mitral regurgitation are at risk of even late postoperative atrial fibrillation (AF). Left atrial (LA) function has been shown superior to LA volume in evaluating the risk of AF in diverse cardiac conditions. We therefore investigated the prognostic value of LA function and volume in predicting mid-to-late postoperative AF after MVr (>30 days postoperatively).

METHODS

We retrospectively identified all patients who underwent MVr for degenerative mitral regurgitation between 2012 and 2019 at our institution. Exclusion criteria were preoperative AF, concomitant procedures, re-operations, missing or insufficiently processable preoperative echocardiograms and missing follow-up. LA function and volume measurements were conducted using speckle-tracking strain echocardiographic analysis. Postoperative LA function was measured in a subgroup with sufficient postoperative echocardiograms.

RESULTS

We included 251 patients, of whom 39 (15.5%) experienced AF in the mid-to-late postoperative period. Reduced LA strain parameters and more than mild preoperative tricuspid regurgitation were independently associated with mid-to-late postoperative AF. LA volume index had no association with mid-to-late postoperative AF in univariable analysis and did not improve the performance of multivariable models. Patients with mid-to-late AF exhibited diminished improvement in LA function after surgery.

CONCLUSIONS

In MVr patients, LA function (but not volume) showed independent predictive value for mid-to-late postoperative AF. Including LA function into surgical decision-making and approach may identify patients who will benefit from earlier intervention with the aim to prevent irreversible LA damage with consequent risk of postoperative AF.
Reduction in inappropriate therapies through device programming in subcutaneous implantable defibrillator patients: data from clinical practice
Authors: Rordorf Roberto , Viani Stefano , Biffi Mauro , Pieragnoli Paolo , Migliore Federico , D’Onofrio Antonio , Nigro Gerardo , Francia Pietro , Ferrari Paola , Dello Russo Antonio , Bisignani Antonio , Ottaviano Luca , Palmisano Pietro , Caravati Fabrizio , Pisanò Ennio , Pani Antonio , Botto Giovanni Luca , Lovecchio Mariolina , Valsecchi Sergio , Vicentini Alessandro
Published: March 2023

Aims

In subcutaneous implantable cardioverter defibrillator (S-ICD) recipients, the UNTOUCHED study demonstrated a very low inappropriate shock rate on programming a conditional zone between 200 and 250 bpm and a shock zone for arrhythmias >250 bpm. The extent to which this programming approach is adopted in clinical practice is still unknown, as is its impact on the rates of inappropriate and appropriate therapies.

Methods and results

We assessed ICD programming on implantation and during follow-up in a cohort of 1468 consecutive S-ICD recipients in 56 Italian centres. We also measured the occurrence of inappropriate and appropriate shocks during follow-up. On implantation, the median programmed conditional zone cut-off was set to 200 bpm (IQR: 200–220) and the shock zone cut-off was 230 bpm (IQR: 210–250). During follow-up, the conditional zone cut-off rate was not significantly changed, while the shock zone cut-off was changed in 622 (42%) patients and the median value increased to 250 bpm (IQR: 230–250) (P < 0.001). UNTOUCHED-like programming of detection cut-offs was adopted in 426 (29%) patients immediately after device implantation, and in 714 (49%, P < 0.001) at the last follow-up. UNTOUCHED-like programming was independently associated with fewer inappropriate shocks (hazard ratio 0.50, 95%CI 0.25–0.98, P = 0.044), and had no impact on appropriate and ineffective shocks.

Conclusions

In recent years, S-ICD implanting centres have increasingly programmed high arrhythmia detection cut-off rates, at the time of implantation in the case of new S-ICD recipients, and during follow-up in the case of pre-existing implants. This has contributed significantly to reducing the incidence of inappropriate shocks in clinical practice.

Rordorf: Programming of the S-ICD  

Clinical Trial Registration

URL: http://clinicaltrials.gov/Identifier: NCT02275637
Impact of peri-procedural management of direct oral anticoagulants on pocket haematoma after cardiac electronic device implantation: the StimAOD multicentre prospective study
Authors: Martin Anne-Céline , Weizman Orianne , Sellal Jean-Marc , Algalarrondo Vincent , Amara Walid , Bouzeman Abdeslam , Gandjbakhch Estelle , Lellouche Nicolas , Louembe Jules , Menet Aymeric , Roumegou Pierre , Treguer Frederic , Godier Anne , Boveda Serge , Garcia Rodrigue , Marijon Eloi
Published: March 2023

Aims

The study aims to investigate the impact of direct oral anticoagulant (DOAC) management on the incidence of pocket haematoma in patients undergoing pacemaker or implantable cardioverter–defibrillator implantation.

Methods and results

All consecutive patients receiving DOAC and undergoing cardiac electronic device implantation were included in a large multicentre prospective observational study (NCT 03879473). The primary endpoint was clinically relevant haematoma within 30 days after implantation. Overall, 789 patients were enrolled [median age 80 (IQR 72–85) years old, 36.4% women, median CHA2DS2-VASc score 4 (IQR 0–8)], of which 632 (80.1%) received a pacemaker implantation. Antiplatelet therapy was combined with DOAC in 146 patients (18.5%). Direct oral anticoagulants (DOACs) were interrupted 52 (IQR 37–62) h before the procedure and resumed 31 (IQR 21–47) h later. Ninety-six percent of the patients had at least 12 h DOAC interruption before the procedure, and 78% had at least 12 h DOAC interruption after the procedure. Overall, anticoagulation was interrupted for 72 (IQR 48–96) h. Pre- or post-procedural heparin bridging was used in 8.2% and 3.9%, respectively. Timing of DOAC interruption of resumption was not associated with clinically relevant haematoma. Clinically relevant haematoma occurred in 26 patients (3.3%), and thromboembolic events occurred in 5 patients (0.6%).

Conclusion

In this large real-life registry where most patients had DOAC interruption, clinically relevant haematoma was rare. Despite DOAC interruption and high CHA2DS2-VASc score, thromboembolic events occurred seldomly, highlighting that bleeding exceeds thromboembolic risk in this peri-procedural period. Future research is needed to identify risk factors for clinically relevant haematoma and meaningfully guide clinicians in optimizing DOAC management.
Twenty-year experience of atrial fibrillation ablation: a single-centre cohort study
Authors: Bottoni Nicola , Quartieri Fabio , Iori Matteo , Battista Antonella , Navazio Alessandro , Brignole Michele
Published: March 2023

Aims

While several studies in the literature have reported results of catheter ablation of AF, few is known regarding outcome for more than 10 years.

Methods and results

The complete population of patients who underwent AF ablation in the years 2002–2021 in the department of cardiology of the hospital of Reggio Emilia has been analysed. The last follow-up was made in the second half of 2022. During this period the technique of ablation remained relatively unchanged as well the physicians performing ablation. Primary endpoint was the recurrence of symptomatic AF, defined as AF that caused symptoms that were defined by the patient as able to alter their quality of life. 669 patients underwent catheter ablation and 618 were followed until 2022. Median age of the patients was 58 ± 9 years and 521 (78%) were male. There were 407 (61%) of patients with paroxysmal AF, 167 (25%) with persistent AF and 95 (14%) with long-lasting AF. A total of 838 procedures were performed, with a mean of 1.25 per patient. 163 (26%) patients had 2 procedures and 6 had 3 ablations. Periprocedural complications occurred in 4.8% of procedures. Follow-up data were available for 618 patients (92.4%). The median follow-up duration was 6.6 years (IQR 3.2–10.8). The estimated recurrence rate of symptomatic AF was 26% at 10 years, 54% at 15 years and 82% at 20 years. The recurrence rate was similar in patients who had performed one procedure and in those who had performed 2 or 3 procedures. Progression to permanent AF occurred in 112 patients (18%). The major events that occurred during the follow-up consisted of total mortality in 4.5%, heart failure in 3.1% and TIA/stroke in 2.4%.

Conclusion

Symptomatic AF tends to recur during long-term follow-up despite one or more procedures. Catheter ablation seems able to reduce the rate of symptomatic recurrences and to delay the time of their occurrence. These findings are consistent with the knowledge that an age-dependent progressive structural atriomiopathy is the basis for the development of AF.
Phenotypic plasticity under the effects of multiple environmental variables
Authors: Hudak Abigail , Dybdahl Mark
Published: March 2023

Organisms exposed to major environmental change face atypical and stressful conditions across multiple environmental variables, yet studies of phenotypically plastic responses historically focus on one environmental variable at a time. Evaluating multivariate plasticity of traits across different, simultaneously varying environmental variables provides new insights into the fate of populations amidst environmental changes. We aimed to investigate plasticity in multivariate environments by (a) examining the individual and joint effects of two environmental variables and (b) calculating genotype-by-environment interactions and genetic correlations of character states to investigate potential evolutionary constraints. We performed a lab controlled-environment experiment under a full factorial design of low and high temperatures and salinities with multiple maternal lineages of a parthenogenetic freshwater snail, Potamopyrgus antipodarum. Our results revealed that predictions of plastic trait responses among multivariate environments may be unexpected due to nonadditive effects of environmental variables and varying magnitudes and orientations of genetic correlations among fitness-related traits. Considering multivariate environments provides deeper insight and advancement of understanding trait evolution by revealing trait patterns that would otherwise be missed in univariate studies.
Contribution of the capsular polysaccharide layer to antibiotic resistance in bifidobacteria
Authors: Argentini Chiara , Tarracchini Chiara , Alessandri Giulia , Longhi Giulia , Milani Christian , van Sinderen Douwe , Ventura Marco , Turroni Francesca
Published: March 2023

Bifidobacteria have been shown to produce exopolysaccharides (EPS), which are polymeric structures composed of various carbohydrates, commonly containing glucose, galactose, and rhamnose. EPS are produced by different bifidobacterial taxa commonly identified in the human gut, such as Bifidobacterium breve and Bifidobacterium longum subsp. longum, and have been suggested to modulate the interaction of bifidobacterial cells with other members of the human gut microbiota as well as with their host. In this study, we evaluated if bifidobacterial EPS production of four selected EPS-producing strains is associated with enhanced resistance to antibiotic treatments through MIC analysis when compared to bacterial cultures that do not produce exopolysaccharides. Our results showed that an increase in EPS production by modifying the growth medium with different carbon sources, i.e. glucose, galactose or lactose and/or by applying stressful conditions, such as bile salts and acidity, is associated with a tolerance enhancement of bifidobacterial cells toward various beta-lactam antibiotics. In addition, after analyzing the production of EPS at the phenotypic level, we explored the genes involved in the production of these structures and evaluated their expression, in presence of various carbon sources, using RNAseq. Overall, this study provides preliminary experimental evidence showing how bifidobacterial EPS modifies the level of susceptibility of these bacteria towards antibiotics.
A deficiency screen of the 3rd chromosome for dominant modifiers of the Drosophila ER integral membrane protein, Jagunal
Authors: Ascencio Gerson , de Cruz Matthew A , Abuel Judy , Alvarado Sydney , Arriaga Yuma , Conrad Emily , Castro Alonso , Eichelberger Katharine , Galvan Laura , Gundy Grace , Garcia Jorge Alberto Inojoza , Jimenez Alyssa , Lu Nhien Tuyet , Lugar Catharine , Marania Ronald , Mendsaikhan Tserendavaa , Ortega Jose , Nand Natasha , Rodrigues Nicole S , Shabazz Khayla , Tam Cynnie , Valenciano Emmanuel , Hayzelden Clive , Eritano Anthony S , Riggs Blake
Published: March 2023

The mechanism surrounding chromosome inheritance during cell division has been well documented, however, organelle inheritance during mitosis is less understood. Recently, the endoplasmic reticulum (ER) has been shown to reorganize during mitosis, dividing asymmetrically in proneuronal cells prior to cell fate selection, indicating a programmed mechanism of inheritance. ER asymmetric partitioning in proneural cells relies on the highly conserved ER integral membrane protein, Jagunal (Jagn). Knockdown of Jagn in the compound Drosophila eye displays a pleotropic rough eye phenotype in 48% of the progeny. To identify genes involved in Jagn dependent ER partitioning pathway, we performed a dominant modifier screen of the 3rd chromosome for enhancers and suppressors of this Jagn-RNAi-induced rough eye phenotype. We screened through 181 deficiency lines covering the 3L and 3R chromosomes and identified 12 suppressors and 10 enhancers of the Jagn-RNAi phenotype. Based on the functions of the genes covered by the deficiencies, we identified genes that displayed a suppression or enhancement of the Jagn-RNAi phenotype. These include Division Abnormally Delayed (Dally), a heparan sulfate proteoglycan, the γ-secretase subunit Presenilin, and the ER resident protein Sec63. Based on our understanding of the function of these targets, there is a connection between Jagn and the Notch signaling pathway. Further studies will elucidate the role of Jagn and identified interactors within the mechanisms of ER partitioning during mitosis.
The trouble with triples: Examining the impact of measurement error in mediation analysis
Authors: Gastonguay Madeleine S , Keele Gregory R , Churchill Gary A
Published: March 2023

Mediation analysis is used in genetic mapping studies to identify candidate gene mediators of quantitative trait loci (QTL). We consider genetic mediation analysis of triplets—sets of three variables consisting of a target trait, the genotype at a QTL for the target trait, and a candidate mediator that is the abundance of a transcript or protein whose coding gene co-locates with the QTL. We show that, in the presence of measurement error, mediation analysis can infer partial mediation even in the absence of a causal relationship between the candidate mediator and the target. We describe a measurement error model and a corresponding latent variable model with estimable parameters that are combinations of the causal effects and measurement errors across all three variables. The relative magnitudes of the latent variable correlations determine whether or not mediation analysis will tend to infer the correct causal relationship in large samples. We examine case studies that illustrate the common failure modes of genetic mediation analysis and demonstrate how to evaluate the effects of measurement error. While genetic mediation analysis is a powerful tool for identifying candidate genes, we recommend caution when interpreting mediation analysis findings.
‘I doe not find him, howsoever our great Enemy, to have deserved such an end’: Reactions to the Assassination of Albrecht von Wallenstein, c.1634–1700
Authors: Pert Thomas
Published: March 2023

Albrecht von Wallenstein was one of the most colourful and controversial figures of the Thirty Years War, and his dismissal by the Holy Roman Emperor Ferdinand II and eventual assassination was one of the most talked about events of the conflict. This article examines how the downfall of the imperial generalissimo and massacre of his subordinate officers at Eger, in Bohemia, were viewed and reported across Europe at various pro- and anti-Habsburg courts. In addition to assessing how Wallenstein’s demise was discussed in diplomatic circles, the article addresses how the events at Eger were portrayed in newsprint published in the German states as well as further afield in Sweden, England and the Italian states. An examination of political and private correspondence, as well as a comparison of news publications from across the continent, provides valuable insight into how information and intelligence were collected and disseminated throughout early modern Europe. By examining the depiction of Wallenstein’s downfall in the arts, such as poetry and stage plays in various European cities in the immediate aftermath of the assassination and in the mid- and later 1630s, it is also possible to determine what information had been received in different locations at different times. The final section of the article addresses how Wallenstein’s reputation had changed by the end of the seventeenth century, with the result that he was almost universally regarded as a notorious rebel and would-be regicide.
‘The Chronicle Must Tell How It Once Was’: Commercial Sex and Pimping in the Chronicle of Hamburg’s Postwar Vice Police
Authors: Martin Annalisa
Published: March 2023

To ‘pass on a bit of recent history’, members of Hamburg’s vice police, or Sitte, gradually assembled a six-volume chronicle covering the period 1945 to 1982. The authors documented promotions, retirements, joint trips and work parties, but they also recorded the work of the department, illustrated through case notes and commentary on pimping, prostitution, pornography, drug use, paedophilia and incest. This article examines the treatment and depiction of commercial sex and pimping from the 1950s into the early 1980s. Central here is an investigation of the portrayals of ‘pimp’ violence towards women who sold sex, viewed alongside allusions to and evidence of police violence. A further focus is the presentation of and relationship with women who sold sex in Hamburg, with particular reference to police commentary regarding their race, sexuality and gender identity. The article also explores descriptions in the chronicle of so-called ‘transvestite’ prostitution. The authors of the chronicle repeatedly allude to sexual liberalization in West German society at large. Their entries are crafted with a reader in mind as they relate the actions of officers and subjects to changing views on sexuality. This article thus also analyses police engagement with processes of sexual liberalization and the implications for the role of the vice police in West Germany.
Resiliency Among Women’s Health Initiative Women Aged 80 and Older by Race, Ethnicity, and Neighborhood Socioeconomic Status
Authors: Krok-Schoen Jessica L , Naughton Michelle J , Felix Ashley S , Wiley Cené Crystal , Springfield Sparkle , Yu Mengda , McLaughlin Eric M , Shadyab Aladdin H , Nolan Timiya S , Kroenke Candyce H , Garcia Lorena , Follis Shawna , Jackson Rebecca D
Published: March 2023

Objectives

A comprehensive examination of resilience by race, ethnicity, and neighborhood socioeconomic status (NSES) among women aged ≥80 is needed, given the aging of the U.S. population, increasing longevity, and growing racial and ethnic diversity.

Methods

Participants were women aged ≥80 enrolled in the Women’s Health Initiative. Resilience was assessed with a modified version of the Brief Resilience Scale. Descriptive statistics and multiple linear regression examined the association of demographic, health, and psychosocial variables with resilience by race, ethnicity, and NSES.

Results

Participants (n = 29,367, median age = 84.3) were White (91.4%), Black (3.7%), Hispanic (1.9%), and Asian (1.7%) women. There were no significant differences by race and ethnicity on mean resiliency scores (p = .06). Significant differences by NSES were observed regarding mean resiliency scores between those with low NSES (3.94 ± 0.83, out of 5) and high NSES (4.00 ± 0.81). Older age, higher education, higher self-rated health, lower stress, and living alone were significant positive correlates of resilience in the sample. Social support was correlated with resilience among White, Black, and Asian women, but not for Hispanic women. Depression was a significant correlate of lower resilience, except among Asian women. Living alone, smoking, and spirituality were significantly associated with higher resilience among women with moderate NSES.

Discussion

Multiple factors were associated with resilience among women aged ≥80 in the Women’s Health Initiative. Despite some differing correlates of resilience by race, ethnicity, and NSES, there were many similarities. These results may aid in the design of resilience interventions for the growing, increasingly diverse population of older women.
Proportionality Defenses in FRAND Cases: a Comparative Assessment of the Revised German Patent Injunction Rules and U.S. Case Law
Authors: Picht Peter Georg , Contreras Jorge L
Published: March 2023

In August 2021, the ‘Second Act for the Modernization of Patent Law’ (Zweites Patentrechtsmoderni-sierungsgesetz) introduced an explicit proportionality defense into Sec. 139(1) German Patent Act. Unlike the competition law or national contract law prong of the Huawei defense in FRAND cases, the proportionality defense thus derives from the GPA itself. The new provision has already generated much debate and some initial case law. According to public knowledge, however, it has not yet been raised in a German FRAND case, although it seems inevitable that this will happen. Hence, this article offers to market participants and the judiciary a proposed analytical framework for considering such a proportionality defense in German FRAND cases. For this purpose, it undertakes a comparative assessment of U.S. patent injunction law. As to German law, the focus is on whether the proportionality defense and the FRAND license defense can be raised in parallel, whether FRAND royalties are a suitable basis for calculating an appropriate financial compensation under Sec. 139(1)(4) and how a court should assess whether the impact of an injunction in a FRAND case triggers the proportionality defense.
The Emperor Has No Clothes: How the Press Publishers’ Right Implementation Exposes Its Shortcomings
Authors: Furgał Ula
Published: March 2023

This article discusses the implementation of the press publishers’ right introduced by Art. 15 of the Directive on Copyright in the Digital Single Market (CDSM). It analyses Member States’ transpositions through the lens of the legislative intent of the EU legislator, who aimed to strengthen the press publishers’ bargaining position towards digital intermediates while preserving users’ freedom to share information online. The article argues that the implementation process further exposes the shortcomings of the press publishers’ right and its unfitness to deliver the goals set. The negotiation basis that the right provides is neither clear, nor capable of correcting bargaining imbalances, as it is unable to force relevant platforms to the negotiation table. The extension of the scope of the press publishers’ right to social media is questionable, as it inherently influences users’ freedoms. The article cautions against the implementation of the press publishers’ right in a way that mimics the solutions endorsed in the competition law-based bargaining codes with the excess of implementation freedoms provided by the CDSM Directive.
Protecting children and young people from contemporary marketing for gambling
Authors: Thomas Samantha , van Schalkwyk May C I , Daube Mike , Pitt Hannah , McGee Darragh , McKee Martin
Published: March 2023

Around the world, children are being exposed to intensive marketing for gambling products. This normalizes perceptions that gambling is essentially a harmless form of entertainment, despite mounting evidence of the harms it causes. Young people and their parents are supportive of strategies to protect children from being exposed to gambling marketing. Yet existing regulatory efforts are inconsistent and inadequate, and have not protected children from exposure to the many forms of marketing now being developed and exploited by the gambling industry. We outline existing knowledge about strategies used by the gambling industry to market its products, with a specific focus on the potential impact of gambling marketing on young people. We provide a definition of gambling marketing and outline the different forms of promotion that are currently used to market gambling, current regulatory responses, and the impact of marketing on children and young people. We then argue that a comprehensive public health approach to gambling is urgently required, which must include effective action to limit the influence of marketing for gambling products, while recognizing that it is never possible to insulate children entirely from their reach.
Characterizing asset-based studies in public health: development of a framework
Authors: Martin-Kerry Jacqueline , McLean Jennifer , Hopkins Trevor , Morgan Antony , Dunn Laurie , Walton Robert , Golder Su , Allison Tim , Cooper Des , Wohland Pia , Prady Stephanie L
Published: March 2023

Asset-based approaches are becoming more common within public health interventions; however, due to variations in terminology, it can be difficult to identify asset-based approaches. The study aimed to develop and test a framework that could distinguish between asset-based and deficit-based community studies, whilst acknowledging there is a continuum of approaches. Literature about asset-based and deficit-based approaches were reviewed and a framework was developed based on the Theory of Change model. A scoring system was developed for each of the five elements in the framework based on this model. Measurement of community engagement was built in, and a way of capturing how much the study involved an asset approach. The framework was tested on 13 studies examining community-based interventions to investigate whether it could characterize asset-based versus deficit-based studies. The framework demonstrated how much the principles underpinning asset-based approaches were present and distinguished between studies where the approach was deficit-based to those that had some elements of an asset-based approach. This framework is useful for researchers and policymakers when determining how much of an intervention is asset-based and identifying which elements of asset-based approaches lead to an intervention working.