bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel Quantification of Real-Time Lymphatic Clearance: Immediate Lymphatic Reconstruction in a Large-Animal Model
Authors: Johnson Anna Rose , Tétrault Marc-André , Bravo Miguel G. , Girouard Vincent , Laurence Rita , Lee Bernard T. , Soo Choi Hak , Singhal Dhruv
Published: December 2021

Background:

The real-time quantification of lymphatic flow remains elusive. Efforts to provide a metric of direct lymphatic function are not clinically translatable and lack reproducibility. Early reports demonstrate the promise of immediate lymphatic reconstruction (immediate lymphovenous bypass after lymphadenectomy) to reduce the risk of lymphedema development. However, there remains a heightened need to appraise this technique in a clinically translatable large-animal model. The aim of the authors’ experiment was to evaluate the role of molecular imaging in the quantification of real-time lymphatic flow after lymphadenectomy, and lymphadenectomy with lymphovenous bypass using novel fluorophores in a swine model.

Methods:

A lymphadenectomy or lymphadenectomy with subsequent lymphovenous bypass was performed in 10 female swine. After subdermal fluorophore injection, near-infrared molecular imaging of blood samples was used to evaluate change in lymphatic flow after lymphadenectomy versus after lymphadenectomy with lymphovenous bypass. Continuous imaging evaluating fluorescence of the superficial epigastric vein in the torso and adjacent skin was performed throughout all experiments. Findings between modalities were correlated.

Results:

The near-infrared dye signal in central and peripheral blood samples was often difficult to separate from background and proved challenging for reliable quantification. Venous and skin near-infrared imaging demonstrated a lymphatic clearance rate decrease of 70 percent after lymphadenectomy versus a decrease by only 30 percent after lymphadenectomy with immediate lymphovenous bypass.

Conclusions:

In this article, the authors describe a noninvasive, swine, large-animal model to quantify lymphatic clearance using skin imaging. The authors’ findings were consistent with results yielded from real-time imaging of the vein. The authors believe this model may have important implications for eventual direct translation to the clinical setting.
Complications in Brachioplasty: A Systematic Review and Meta-Analysis
Authors: Aljerian Albaraa , Abi-Rafeh Jad , Ramirez-GarciaLuna José , Hemmerling Thomas , Gilardino Mirko S.
Published: December 2021

Background:

Brachioplasty procedures have experienced a surge in popularity over the past decade, mirroring the rise in bariatric procedures and growing population of massive weight loss patients. The authors estimated the incidence of associated complications and identify possible patient- or procedure-related predictive factors.

Methods:

A systematic review was performed using the PubMed, Cochrane, and Embase databases; extracted data were synthesized through a random-effects meta-analysis of proportions and a multivariate meta-regression.

Results:

Twenty-nine studies were included in the meta-analysis, representing 1578 patients; all studies followed an observational design. The incidence of adverse outcomes assessed included aberrant scarring, 9.9 percent (95 percent CI, 6.1 to 15.6 percent); ptosis or recurrence, 7.79 percent (95 percent CI, 4.8 to 12.35 percent); wound dehiscence, 6.81 percent (95 percent CI, 4.63 to 9.90 percent); seroma, 5.91 percent (95 percent CI, 3.75 to 9.25 percent); infection, 3.64 percent (95 percent CI, 2.38 to 5.53 percent); nerve-related complications, 2.47 percent (95 percent CI, 1.45 to 4.18 percent); lymphedema or lymphocele formation, 2.46 percent (95 percent CI, 1.55 to 3.88 percent); skin necrosis or delayed healing, 2.27 percent (95 percent CI, 1.37 to 3.74 percent); and hematoma, 2.06 percent (95 percent CI, 1.38 to 3.06 percent). The operative reintervention rate for aesthetic purposes was 7.46 percent (95 percent CI, 5.05 to 10.88 percent), and the operative reintervention rate for nonaesthetic purposes was 1.62 percent (95 percent CI, 1.00 to 2.61 percent). Multivariate meta-regression demonstrated that medial incision placement was associated with a higher risk of complications, whereas the incidence of certain complications was lowered with adjunctive liposuction (p < 0.05).

Conclusion:

In the absence of large clinical trials, the present meta-analysis can serve to provide plastic surgeons with an evidence-based reference to improve informed consent and guide procedure selection with respect to the complication profile of brachioplasty.
Facial Gender Surgery: Systematic Review and Evidence-Based Consensus Guidelines from the International Facial Gender Symposium
Authors: Coon Devin , Berli Jens , Oles Norah , Mundinger Sol , Thomas Kate , Meltzer Toby , Houssock Carrie , Satterwhite Thomas , Morrison Shane , Bailón Carlos , Tenório Thiago , Simon Daniel , Capitán-Cañadas Fermín , Capitán Luis
Published: December 2021

Background:

Increasing societal acceptance of transgender people has led to broader availability of gender surgery and rapid growth in transition-related operations. Facial gender surgery aims to modify patients’ facial features to be more congruent with their physical expression of gender, reducing gender dysphoria and improving quality of life. Growth in research and technique evolution has not kept pace with growth in clinical volume. Therefore, the first International Facial Gender Symposium was held at Johns Hopkins University in 2019, convening surgeons who perform facial gender surgery to share ideas and assess the state of clinical evidence.

Methods:

To review the literature on facial gender surgery, the authors developed a search strategy for seven electronic databases (PubMed, PsycINFO, Embase, CINAHL, Web of Science, Cochrane, and Gender Studies) through May of 2019, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses systematic review guidelines.

Results:

Based on the English language literature and clinical experience, the authors suggest guidelines for screening, management, and appropriate surgical technique for patients undergoing facial gender surgery. They highlight facial gender surgery as a medically necessary intervention and identify shortcomings in current guidelines.

Conclusions:

Facial gender surgery represents a complex array of craniofacial and soft-tissue procedures that require application of advanced skills and decision-making. Facial gender operations are not cosmetic, are medically necessary, and require development of new CPT codes specific to facial gender surgery. It is imperative to create educational programs and methods to define sufficient training for facial gender surgery surgeons. Research priorities include better procedural outcomes data, more quality-of-life studies, and insight into variation in both patient and procedural subgroups.
Fat Grafting before Delayed Prophylactic Mastectomy and Immediate Implant Reconstruction for Patients at High Risk of Complications
Authors: Lesniak David M. , Sarfati Isabelle , Meredith Ineke , Millochau Jenny , Wang Kuan-Chi , Nos Claude , Clough Krishna B.
Published: December 2021

The majority of patients undergoing bilateral prophylactic mastectomy request immediate implant-based breast reconstruction. Some patients, especially those with prior radiotherapy, are at increased risk of early cutaneous complications and implant loss. The authors developed the technique of primary fat grafting before delayed prophylactic mastectomy to minimize early complications for selective high-risk patients. They have completed 21 cases in 14 patients, 10 of whom had previous lumpectomy and radiation treatment for breast cancer. A single session of fat grafting, with a median injection volume of 250 ml (interquartile range, 200 to 300 ml), was performed a median period of 19 weeks (interquartile range, 16 to 28 weeks) before prophylactic mastectomy. All cases were direct-to-implant reconstruction using textured silicone implants. The median implant volume was 410 ml (interquartile range, 318 to 450 ml). A minor early complication developed in 14 percent of cases (three of 21), with no early implant loss. At a median follow-up of 9 months (interquartile range, 5 to 27 months), the authors found no cases of implant loss and an excellent or good aesthetic outcome (score of 5 or 4) in 16 of 21 cases (76 percent). Fat grafting before prophylactic mastectomy is a novel strategy to minimize early complications and avoid implant loss in patients at high risk of postoperative complications. 

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
A Guide to Industry Payments and an Algorithm for Their Management
Authors: Isbester Kelsey A. , Boas Samuel R. , Wee Corinne , Summerville Lesley , Kumar Anand R.
Published: December 2021

Background:

The Open Payments database was created to increase transparency of industry payment relationships within medicine. The current literature often examines only 1 year of the database. In this study, the authors use 5 years of data to show trends among industry payments to plastic surgeons from 2014 to 2018. In addition, the authors lay out the basics of conflict-of-interest reporting for the new plastic surgeon. Finally, the authors suggest an algorithm for the responsible management of industry relationships.

Methods:

This study analyzed nonresearch payments made to plastic surgeons from January 1, 2014, to December 31, 2018. Descriptive statistics were calculated using R Statistical Software and visualized using Tableau.

Results:

A total of 304,663 payments totaling $140,889,747 were made to 8148 plastic surgeons; 41 percent ($58.28 million) was paid to 50 plastic surgeons in the form of royalty or license payments. With royalties excluded, average and median payments were $276 and $25. The average yearly total per physician was $2028. Of the 14 payment categories, 95 percent of the total amount paid was attributable payments in one of six categories. Seven hundred thirty companies reported payments to plastic surgeons from 2014 to 2018; 15 companies (2 percent) were responsible for 80 percent ($66.34 million) of the total sum paid. Allergan was responsible for $24.45 million (29.6 percent) of this amount.

Conclusions:

Although discussions on the proper management of industry relationships continue to evolve, the data in this study illustrate the importance of managing industry relationships. The simple guidelines suggested create a basis for managing industry relationships in the career of the everyday plastic surgeon.
Aesthetic Repair of Unilateral Cleft Lip using the Modified Inferior Triangle and Adjunctive Techniques
Authors: Parsaei Yassmin , Chandler Ludmilla , Smetona John T. , Lopez Joseph , Steinbacher Derek
Published: December 2021

Surgical management of unilateral cleft lip is challenging. Correction requires a comprehensive approach to ensure optimal aesthetic outcomes. Various techniques have been proposed for the repair of cleft lip. This article and video vignette highlight the senior author’s (D.S.) preferred method for repair of a unilateral cleft lip using a modified inferior triangle technique, a Noordhoff triangular flap for vermillion augmentation, orbicularis oris chemodenervation to reduce tension at the repair site, and autologous fat grafting for lip sculpting.
Syndactyly Release in the Hand: Surgical Technique
Authors: Sood Ravi F. , Irwin Timothy J. , Taghinia Amir H.
Published: December 2021

Syndactyly is one of the most common congenital differences treated by hand surgeons. Although dozens of techniques for syndactyly release have been described, a reliable method is based on a dorsal rectangular flap for commissure construction and a combination of interdigitating zigzag flaps and skin grafts for digital coverage. In this article, the authors present a detailed description of syndactyly release emphasizing principles integral to successful outcomes.
Factors Associated With the Quality of the Patient-Doctor Relationship
Authors: Pascual-Ramos Virginia , Contreras-Yáñez Irazú , Ortiz-Haro Ana Belén , Molewijk Albert Christiaan , Obrador Gregorio T. , Agazzi Evandro
Published: December 2021

Background

The patient-doctor relationship (PDR) is a complex phenomenon with strong cultural determinants, which impacts health-related outcomes and, accordingly, does have ethical implications. The study objective was to describe the PDR from medical encounters between 600 Mexican outpatients with rheumatic diseases and their attending rheumatologists, and to identify factors associated with a good PDR.

Methods

A cross-sectional study was performed. Patients completed the PDRQ-9 (Patient-Doctor Relationship Questionnaire, 9 items), the HAQ-DI (Health Assessment Questionnaire Disability Index), the Short-Form 36 items (SF-36), a pain–visual analog scale, and the Ideal Patient Autonomy Scale. Relevant sociodemographic, disease-related, and treatment-related variables were obtained. Patients assigned a PDRQ-9 score to each patient-doctor encounter. Regression analysis was used to identify factors associated with a good PDR, which was defined based on a cutoff point established using the borderline performance method.

Results

Patients were primarily middle-aged female subjects (86%), with substantial disease duration (median, 11.1 years), without disability (HAQ-DI within reference range, 55.3%), and with deteriorated quality of life (SF-36 out of reference range, 73.7%–78.6%). Among them, 36.5% had systemic lupus erythematosus and 31.8% had rheumatoid arthritis. There were 422 patients (70.3%) with a good PDR and 523 medical encounters (87.2%) involved certified rheumatologists.

Patient paternalistic ideal of autonomy (odds ratio [OR], 3.029; 95% confidence interval [CI], 1.793–5.113), SF-36 score (OR, 1.014; 95% CI, 1.003–1.025), female sex (OR, 0.460; 95% CI, 0.233–0.010), and being certified rheumatologist (OR, 1.526; 95% CI, 1.059–2.200) were associated with a good PDR.

Conclusions

Patient-related factors and the degree of experience of the attending physician impact the quality of the PDR, in Mexican outpatients with rheumatic diseases.
Impact of a Digital Cognitive Aid on the Performance of Military Healthcare Teams During Critical Care Management in a Warfront Injury Situation
Authors: Paraschiv Andrei-Petru , Cejka Jean-Christophe , Lilot Marc , Aigle Luc , Lehot Jean-Jacques , Balança Baptiste
Published: December 2021

Introduction

Initial healthcare delivery after warfront injury is unpredictably challenging for military forces. As preparatory training, healthcare providers use simulation to improve their performance in stressful critical situations. This study investigated whether a digital CA held by the team leader improved performance in simulated combat casualty care.

Methods

This randomized controlled trial was performed during a combat casualty training course for military physicians and nurses in France. Each pair of care providers completed 2 scenarios randomized to be undertaken either with or without a digital CA. The primary end point was the technical performance evaluated from a video recording by 2 independent raters using a pre-established score grid (up to 100%) according to military protocols. The secondary end point was the nontechnical performance (TEAM scale, maximum: 54 points).

Results

Thirty-six pairs of participants were included. Use of the digital CA improved both technical (74% vs 53%, P < 0.001) and nontechnical (42 vs 32, P < 0.001) performance.

Conclusions

The digital CA improved technical and nontechnical performance during training of medical care for military combat casualties. Use of a dedicated digital CA might improve care in a combat environment.

Study Type

This study is a randomized controlled trial.
Prognostic factors associated with development of infected necrosis in patients with acute necrotizing or severe pancreatitis—A systematic review and meta-analysis
Authors: Tran Alexandre , Fernando Shannon M. , Rochwerg Bram , Inaba Kenji , Bertens Kimberly A. , Engels Paul T. , Balaa Fady K. , Kubelik Dalibor , Matar Maher , Lenet Tori I. , Martel Guillaume
Published: December 2021

PURPOSE

Acute pancreatitis is a potentially life-threatening condition with a wide spectrum of clinical presentation and illness severity. An infection of pancreatic necrosis (IPN) results in a more than twofold increase in mortality risk as compared with patients with sterile necrosis. We sought to identify prognostic factors for the development of IPN among adult patients with severe or necrotizing pancreatitis.

METHODS

We conducted this prognostic review in accordance with systematic review methodology guidelines. We searched six databases from inception through March 21, 2021. We included English language studies describing prognostic factors associated with the development of IPN. We pooled unadjusted odds ratio (uOR) and adjusted odds ratios (aOR) for prognostic factors using a random-effects model. We assessed risk of bias using the Quality in Prognosis Studies tool and certainty of evidence using the GRADE approach.

RESULTS

We included 31 observational studies involving 5,210 patients. Factors with moderate or higher certainty of association with increased IPN risk include older age (uOR, 2.19; 95% confidence interval [CI], 1.39–3.45, moderate certainty), gallstone etiology (aOR, 2.35; 95% CI, 1.36–4.04, high certainty), greater than 50% necrosis of the pancreas (aOR, 3.61; 95% CI, 2.15–6.04, high certainty), delayed enteral nutrition (aOR, 2.09; 95% CI, 1.26–3.47, moderate certainty), multiple or persistent organ failure (aOR, 11.71; 95% CI, 4.97–27.56, high certainty), and invasive mechanical ventilation (uOR, 12.24; 95% CI, 2.28–65.67, high certainty).

CONCLUSION

This meta-analysis confirms the association between several clinical early prognostic factors and the risk of IPN development among patients with severe or necrotizing pancreatitis. These findings provide the foundation for the development of an IPN risk stratification tool to guide more targeted clinical trials for prevention or early intervention strategies.

LEVEL OF EVIDENCE

Systematic review and meta-analysis, Level IV.
Dogs' looking times and pupil dilation response reveal expectations about contact causality
Authors: Völter Christoph J. , Huber Ludwig
Published: December 2021

Contact causality is one of the fundamental principles allowing us to make sense of our physical environment. From an early age, humans perceive spatio-temporally contiguous launching events as causal. Surprisingly little is known about causal perception in non-human animals, particularly outside the primate order. Violation-of-expectation paradigms in combination with eye-tracking and pupillometry have been used to study physical expectations in human infants. In the current study, we establish this approach for dogs (
Canis familiaris
). We presented dogs with realistic three-dimensional animations of launching events with contact (regular launching event) or without contact between the involved objects. In both conditions, the objects moved with the same timing and kinematic properties. The dogs tracked the object movements closely throughout the study but their pupils were larger in the no-contact condition and they looked longer at the object initiating the launch after the no-contact event compared to the contact event. We conclude that dogs have implicit expectations about contact causality.
Developing a morphomics framework to optimize implant site-specific design parameters for islet macroencapsulation devices
Authors: McDermott Barry , Robinson Scott , Holcombe Sven , Levey Ruth E. , Dockery Peter , Johnson Paul , Wang Stewart , Dolan Eimear B. , Duffy Garry P.
Published: December 2021

Delivering a clinically impactful cell number is a major design challenge for cell macroencapsulation devices for Type 1 diabetes. It is important to understand the transplant site anatomy to design a device that is practical and that can achieve a sufficient cell dose. We identify the posterior rectus sheath plane as a potential implant site as it is easily accessible, can facilitate longitudinal monitoring of transplants, and can provide nutritive support for cell survival. We have investigated this space using morphomics across a representative patient cohort (642 participants) and have analysed the data in terms of gender, age and BMI. We used a shape optimization process to maximize the volume and identified that elliptical devices achieve a clinically impactful cell dose while meeting device manufacture and delivery requirements. This morphomics framework has the potential to significantly influence the design of future macroencapsulation devices to better suit the needs of patients.
New light on the role of instruments in exploration during the 1830s
Authors: Wess Jane
Published: December 2021

This paper sets out a new interpretation of the agency of scientific instruments in the field. It uses Actor Network Theory as a conceptual framework, which invokes the concept of non-human agency, meaning that scientific instruments can affect outcomes and processes. It argues that the instruments taken on expeditions by travellers on behalf of the Royal Geographical Society (RGS) had agency in knowledge creation simply by being present. Having bequeathed the instruments, the RGS had sanctioned the expedition, and knowledge had to result regardless of whether the instruments had been utilized as intended. The paper builds on the work of historians on the morality of precision, but, by engaging in a detailed comparison of rhetoric and action in two case studies, it suggests a different approach. Observing the strategies of the RGS for knowledge creation in varying circumstances, it argues that the instruments had agency owing to their embedded resource rather than their tangible numerical outputs. The instruments did not always work as mediators between humans and natural phenomena, as the human actants were not able to exploit them as such. Nevertheless, they had agency in knowledge creation as their presence ensured success. The paper is based on published and unpublished material, the latter in the RGS–Institute of British Geographers archives.
Modelling social readers: novel tools for addressing reception from online book reviews
Authors: Holur Pavan , Shahsavari Shadi , Ebrahimzadeh Ehsan , Tangherlini Timothy R. , Roychowdhury Vwani
Published: December 2021

Social reading sites offer an opportunity to capture a segment of readers’ responses to literature, while data-driven analysis of these responses can provide new critical insight into how people ‘read’. Posts discussing an individual book on the social reading site,Goodreads, are referred to as ‘reviews’, and consist of summaries, opinions, quotes or some mixture of these. Computationally modelling these reviews allows one to discover the non-professional discussion space about a work, including an aggregated summary of the work’s plot, an implicit sequencing of various subplots and readers’ impressions of main characters. We develop a pipeline of interlocking computational tools to extract a representation of this reader-generated shared narrative model. Using a corpus of reviews of five popular novels, we discover readers’ distillation of the novels’ main storylines and their sequencing, as well as the readers’ varying impressions of characters in the novel. In so doing, we make three important contributions to the study of infinite-vocabulary networks: (i) an automatically derived narrative network that includes meta-actants; (ii) a sequencing algorithm, REV2SEQ, that generates a consensus sequence of events based on partial trajectories aggregated from reviews, and (iii) an ‘impressions’ algorithm, SENT2IMP, that provides multi-modal insight into readers’ opinions of characters.
Robust finite automata in stochastic chemical reaction networks
Authors: Arredondo David , Lakin Matthew R.
Published: December 2021

Finite-state automata (FSA) are simple computational devices that can nevertheless illustrate interesting behaviours. We propose that FSA can be employed as control circuits for engineered stochastic biological and biomolecular systems. We present an implementation of FSA using counts of chemical species in the range of hundreds to thousands, which is relevant for the counts of many key molecules such as mRNAs in prokaryotic cells. The challenge here is to ensure a robust representation of the current state in the face of stochastic noise. We achieve this by using a multistable approximate majority algorithm to stabilize and store the current state of the system. Arbitrary finite state machines can thus be compiled into robust stochastic chemical automata. We present two variants: one that consumes its input signals to initiate state transitions and one that does not. We characterize the state change dynamics of these systems and demonstrate their application to solve the four-bit binary square root problem. Our work lays the foundation for the use of chemical automata as control circuits in bioengineered systems and biorobotics.
Hunter–gatherer foraging networks promote information transmission
Authors: Garg Ketika , Padilla-Iglesias Cecilia , Restrepo Ochoa Nicolás , Knight V. Bleu
Published: December 2021

Central-place foraging (CPF), where foragers return to a central location (or home), is a key feature of hunter–gatherer social organization. CPF could have significantly changed hunter–gatherers’ spatial use and mobility, altered social networks and increased opportunities for information-exchange. We evaluated whether CPF patterns facilitate information-transmission and considered the potential roles of environmental conditions, mobility strategies and population sizes. We built an agent-based model of CPF where agents moved according to a simple optimal foraging rule, and could encounter other agents as they moved across the environment. They either foraged close to their home within a given radius or moved the location of their home to new areas. We analysed the interaction networks arising under different conditions and found that, at intermediate levels of environmental heterogeneity and mobility, CPF increased global and local network efficiencies as well as the rate of contagion-based information-transmission. We also found that central-place mobility strategies can further improve information transmission in larger populations. Our findings suggest that the combination of foraging and movement strategies, as well as the environmental conditions that characterized early human societies, may have been a crucial precursor in our species’ unique capacity to innovate, accumulate and rely on complex culture.
Sex-biased demography modulates male harm across the genome
Authors: Hitchcock Thomas J. , Gardner Andy
Published: December 2021

Recent years have seen an explosion of theoretical and empirical interest in the role that kin selection plays in shaping patterns of sexual conflict, with a particular focus on male harming traits. However, this work has focused solely on autosomal genes, and as such it remains unclear how demography modulates the evolution of male harm loci occurring in other portions of the genome, such as sex chromosomes and cytoplasmic elements. To investigate this, we extend existing models of sexual conflict for application to these different modes of inheritance. We first analyse the general case, revealing how sex-specific relatedness, reproductive value and the intensity of local competition combine to determine the potential for male harm. We then analyse a series of demographically explicit models, to assess how dispersal, overlapping generations, reproductive skew and the mechanism of population regulation affect sexual conflict across the genome, and drive conflict between nuclear and cytoplasmic genes. We then explore the effects of sex biases in these demographic parameters, showing how they may drive further conflicts between autosomes and sex chromosomes. Finally, we outline how different crossing schemes may be used to identify signatures of these intragenomic conflicts.
Population collapse of habitat-forming species in the Mediterranean: a long-term study of gorgonian populations affected by recurrent marine heatwaves
Authors: Gómez-Gras D. , Linares C. , López-Sanz A. , Amate R. , Ledoux J. B. , Bensoussan N. , Drap P. , Bianchimani O. , Marschal C. , Torrents O. , Zuberer F. , Cebrian E. , Teixidó N. , Zabala M. , Kipson S. , Kersting D. K. , Montero-Serra I. , Pagès-Escolà M. , Medrano A. , Frleta-Valić M. , Dimarchopoulou D. , López-Sendino P. , Garrabou J.
Published: December 2021

Understanding the resilience of temperate reefs to climate change requires exploring the recovery capacity of their habitat-forming species from recurrent marine heatwaves (MHWs). Here, we show that, in a Mediterranean highly enforced marine protected area established more than 40 years ago, habitat-forming octocoral populations that were first affected by a severe MHW in 2003 have not recovered after 15 years. Contrarily, they have followed collapse trajectories that have brought them to the brink of local ecological extinction. Since 2003, impacted populations of the red gorgonian
Paramuricea clavata
(Risso, 1826) and the red coral
Corallium rubrum
(Linnaeus, 1758) have followed different trends in terms of size structure, but a similar progressive reduction in density and biomass. Concurrently, recurrent MHWs were observed in the area during the 2003–2018 study period, which may have hindered populations recovery. The studied octocorals play a unique habitat-forming role in the coralligenous assemblages (i.e. reefs endemic to the Mediterranean Sea home to approximately 10% of its species). Therefore, our results underpin the great risk that recurrent MHWs pose for the long-term integrity and functioning of these emblematic temperate reefs.
Integrated Proteomic and Metabolomic Analyses of the Mitochondrial Neurodegenerative Disease MELAS
Authors: Li Haorong , Uittenbogaard Martine , Navarro Ryan , Ahmed Mustafa , Gropman Andrea , Chiaramello Anne , Hao Ling
Published: December 2021

MELAS (mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes) is a progressive neurodegenerative disease caused by pathogenic mitochondrial DNA variants. The pathogenic mechanism of MELAS remains enigmatic due to the exceptional clinical heterogeneity and the obscure genotype-phenotype correlation among MELAS patients. To gain insights into the pathogenic signature of MELAS, we designed a comprehensive strategy integrating proteomics and metabolomics in patient-derived dermal fibroblasts harboring the ultra-rare MELAS pathogenic variant m.14453G>A, specifically affecting the mitochondrial respiratory Complex I. Global proteomics was achieved by data-dependent acquisition (DDA) and verified by data-independent acquisition (DIA) using both Spectronaut and the recently launched MaxDIA platforms. Comprehensive metabolite coverage was achieved for both polar and nonpolar metabolites in both reverse phase and HILIC LC-MS/MS analyses. Our proof-of-principle MELAS study with multi-omics integration revealed OXPHOS dysregulation with a predominant deficiency of Complex I subunits, as well as alterations in key bioenergetic pathways, glycolysis, tricarboxylic acid cycle, and fatty acid β-oxidation. The most clinically relevant discovery is the downregulation of the arginine biosynthesis pathway, likely due to blocked argininosuccinate synthase, which is congruent with the MELAS cardinal symptom of stroke-like episodes and its current treatment by arginine infusion. In conclusion, we demonstrated an integrated proteomic and metabolomic strategy for patient-derived fibroblasts, which has great clinical potential to discover therapeutic targets and design personalized interventions after validation with a larger patient cohort in the future.

Abstract Figure

Graphic Abstract:

Integrated proteomics and metabolomics of patient fibroblasts revealed dysregulations in arginine biosynthesis, OXPHOS complexes, and bioenergetic pathways in MELAS, a mitochondrial neurodegenerative disease caused by mitochondrial DNA mutations.
Pattern similarity in the frontoparietal control network reflects an “off-veridical” template that optimizes target-match decisions during visual search
Authors: Yu Xinger , Geng Joy J.
Published: December 2021

Theories of attention hypothesize the existence of an “attentional” or “target” template that contains task-relevant information in memory when searching for an object. The target template contributes to visual search by directing visual attention towards potential targets and serving as a decisional boundary for target identification. However, debate still exists regarding how template information is stored in the human brain. Here, we conducted a pattern-based fMRI study to assess how template information is encoded to optimize target-match decisions during visual search. To ensure that match decisions reflect visual search demands, we used a visual search paradigm in which all distractors were linearly separable but highly similar to the target and were known to shift the target representation away from the distractor features (Yu & Geng, 2019). In a separate match-to-sample probe task, we measured the target representation used for match decisions across two resting state networks that have long been hypothesized to maintain and control target information: the frontoparietal control network (FPCN) and the visual network (VisN). Our results showed that lateral prefrontal cortex in FPCN maintained the context-dependent “off-veridical” template; in contrast, VisN encoded a veridical copy of the target feature during match decisions. By using behavioral drift diffusion modeling, we verified that the decision criterion during visual search and the probe task relied on a common biased target template. Taken together, our results suggest that sensory-veridical information is transformed in lateral prefrontal cortex into an adaptive code of target-relevant information that optimizes decision processes during visual search.
Evaluating a communication aid for return of genetic results in families with hypertrophic cardiomyopathy: A randomized controlled trial
Authors: Burns Charlotte , Yeates Laura , Sweeting Joanna , Semsarian Christopher , Ingles Jodie
Published: December 2021

Introduction

Genetic testing for hypertrophic cardiomyopathy (HCM) is considered a key aspect of management. Communication of genetic test results to the proband and their family members, can be a barrier to effective uptake. We hypothesized that a communication aid would facilitate effective communication, and sought to evaluate knowledge and communication of HCM risk to at-risk relatives.

Methods

This was a prospective randomized controlled trial. Consecutive HCM patients attending a specialized clinic, who agreed to participate, were randomized to the intervention or current clinical practice. The intervention consisted of a genetic counselorled appointment, separate to their clinical cardiology review, and guided by a communication booklet which could be written in and taken home. Current clinical practice was defined as the return of the genetic result by a genetic counselor and cardiologist, often as part of a clinical cardiology review. The primary outcome was the ability and confidence of the individual to communicate genetic results to at-risk relatives.

Results

The a priori outcome of improved communication amongst HCM families did not show statistically significant differences between the control and intervention group, though the majority of probands in the intervention group achieved fair communication (n=13/22) and had higher genetic knowledge scores than those in the control group (7 ± 3 versus 6 ± 3). A total of 29% of at-risk relatives were not informed of a genetic result in their family.

Conclusion

Communication amongst HCM families remains challenging, with nearly a third of at-risk relatives not informed of a genetic result. We show a significant gap in the current approach to supporting family communication about genetics.

Australian New Zealand Clinical Trials Registry: ACTRN12617000706370

What is known about this topic

Communication between family members regarding genetic testing can be a barrier to effective uptake.

What this paper adds to the topic

Communication is a challenge in HCM families, with nearly a third of at-risk relatives not informed of a genetic result. There is a significant gap in the current approaches to supporting family communication about genetics.
Real-world clinical outcomes of treatment with casirivimab-imdevimab among patients with mild-to-moderate coronavirus disease 2019 during the Delta variant pandemic
Authors: Suzuki Yasuhito , Shibata Yoko , Minemura Hiroyuki , Nikaido Takefumi , Tanino Yoshinori , Fukuhara Atsuro , Kanno Ryuzo , Saito Hiroyuki , Suzuki Shuzo , Ishii Taeko , Inokoshi Yayoi , Sando Eiichiro , Sakuma Hirofumi , Kobayashi Tatsuho , Kume Hiroaki , Kamimoto Masahiro , Aoki Hideko , Takama Akira , Kamiyama Takamichi , Nakayama Masaru , Saito Kiyoshi , Tanigawa Koichi , Sato Masahiko , Kanbe Toshiyuki , Kanzaki Norio , Azuma Teruhisa , Sakamoto Keiji , Nakamura Yuichi , Otani Hiroshi , Waragai Mitsuru , Maeda Shinsaku , Ishida Tokiya , Sugino Keishi , Tsukada Yasuhiko , Yamada Ryuki , Sato Riko , Omuna Takumi , Tomita Hikaru , Saito Mikako , Watanabe Natsumi , Rikimaru Mami , Kawamata Takaya , Umeda Takashi , Morimoto Julia , Togawa Ryuichi , Sato Yuki , Saito Junpei , Kanazawa Kenya , Iseki Ken
Published: December 2021

Background

Mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may reduce the efficacy of neutralizing monoclonal antibody therapy against coronavirus disease 2019 (COVID-19). We here evaluated the efficacy of casirivimab-imdevimab in patients with mild-to-moderate COVID-19 during the Delta variant surge in Fukushima Prefecture, Japan.

Methods

We enrolled 949 patients with mild-to-moderate COVID-19 who were admitted to hospital between July 24, 2021 and September 30, 2021. Clinical deterioration after admission was compared between casirivimab-imdevimab users (n = 314) and non-users (n = 635).

Results

The casirivimab-imdevimab users were older (P < 0.0001), had higher body temperature (≥ 38°C) (P < 0.0001) and greater rates of history of cigarette smoking (P = 0.0068), hypertension (P = 0.0004), obesity (P < 0.0001), and dyslipidemia (P < 0.0001) than the non-users. Multivariate logistic regression analysis demonstrated that receiving casirivimab-imdevimab was an independent factor for preventing deterioration (odds ratio 0.448; 95% confidence interval 0.263–0.763; P = 0.0023). Furthermore, in 222 patients who were selected from each group after matching on the propensity score, deterioration was significantly lower among those receiving casirivimab-imdevimab compared to those not receiving casirivimab-imdevimab (7.66% vs 14.0%; p = 0.021).

Conclusion

This real-world study demonstrates that casirivimab-imdevimab contributes to the prevention of deterioration in COVID-19 patients after hospitalization during a Delta variant surge.

This real-world retrospective study demonstrates the contribution of treatment with casirivimab-imdevimab to the prevention of deterioration in patients with mild-to-moderate coronavirus disease 2019 (COVID-19) even during the Delta variant pandemic.
Photothermal Dye-based Subcellular-sized Heat Spot Enabling the Modulation of Local Cellular Activities
Authors: Ferdinandus  , Suzuki Madoka , Harada Yoshie , Sarker Satya Ranjan , Ishiwata Shin’ichi , Kitaguchi Tetsuya , Arai Satoshi
Published: December 2021

Thermal engineering at microscale such as the control and measurement of temperature is a key technology in basic biological research and biomaterials development, which remains challenge yet. Here, we engineered the polymeric nanoparticle, in which a fluorescent temperature sensory dye and a photothermal dye were embedded in its polymer matrices, termed nanoHT. When a near infrared laser at 808 nm is illuminated to the particle, it enables to create the subcellular-sized heat spot in a live cell, where fluorescence thermometry allows the read out of the temperature increment concurrently at individual heat spots. Owing to the controlled local heating, we found that the cell death of HeLa cells was induced at the certain temperature at rate of a few seconds. It should be also noted that the cell death was triggered from the very local heat spot at subcellular level. Furthermore, nanoHT was applied for the induction of muscle contraction of the C2C12 myotube by heat. We successfully showed that the heat-induced contraction took place at the limited area of a single myotube according to the alteration of protein-protein interactions related to the contraction event. These studies demonstrated that even a single heat spot provided by a photothermal material could be very effective in altering cellular functions, paving the way for novel photothermal therapies.
A Parameter-free Deep Embedded Clustering Method for Single-cell RNA-seq Data
Authors: Zeng Yuansong , Wei Zhuoyi , Zhong Fengqi , Pan Zixiang , Lu Yutong , Yang Yuedong
Published: December 2021

Clustering analysis is widely utilized in single-cell RNA-sequencing (scRNA-seq) data to discover cell heterogeneity and cell states. While many clustering methods have been developed for scRNA-seq analysis, most of these methods require to provide the number of clusters. However, it is not easy to know the exact number of cell types in advance, and experienced determination is not always reliable. Here, we have developed ADClust, an automatic deep embedding clustering method for scRNA-seq data, which can accurately cluster cells without requiring a predefined number of clusters. Specifically, ADClust first obtains low-dimensional representation through pre-trained autoencoder, and uses the representations to cluster cells into initial micro-clusters. The clusters are then compared in between by a statistical test, and similar micro-clusters are merged into larger clusters. According to the clustering, cell representations are updated so that each cell will be pulled toward centres of its assigned cluster and similar clusters, while cells are separated to keep distances between clusters. This is accomplished through jointly optimizing the carefully designed clustering and autoencoder loss functions. This merging process continues until convergence. ADClust was tested on eleven real scRNA-seq datasets, and shown to outperform existing methods in terms of both clustering performance and the accuracy on the number of the determined clusters. More importantly, our model provides high speed and scalability for large datasets.
Dynamic collateral sensitivity profiles highlight challenges and opportunities for optimizing antibiotic sequences
Authors: Maltas Jeff , Huynh Anh , Wood Kevin B.
Published: December 2021

As failure rates for traditional antimicrobial therapies escalate, recent focus has shifted to evolution-based therapies to slow resistance. Collateral sensitivity–the increased susceptibility to one drug associated with evolved resistance to a different drug–offers a potentially exploitable evolutionary constraint, but the manner in which collateral effects emerge over time is not well understood. Here, we use laboratory evolution in the opportunistic pathogen E. faecalis to phenotypically characterize collateral profiles through evolutionary time. Specifically, we measure collateral profiles for 400 strain-antibiotic combinations over the course of 4 evolutionary time points as strains are selected in increasing concentrations of antibiotic. We find that at a global level–when results from all drugs are combined–collateral resistance dominates during early phases of adaptation, when resistance to the selecting drug is lower, while collateral sensitivity becomes increasingly likely with further selection. At the level of individual populations, however, the trends are idiosyncratic; for example, the frequency of collateral sensitivity to ceftriaxone increases over time in isolates selected by linezolid but decreases is isolates selected by ciprofloxacin. Finally, we show experimentally how dynamic collateral sensitivity relationships can lead to time-dependent dosing windows that depend on finely timed switching between drugs.
Simultaneous CUT&Tag profiling of the accessible and silenced regulome in single cells
Authors: Janssens Derek H. , Otto Dominik J. , Meers Michael P. , Setty Manu , Ahmad Kami , Henikoff Steven
Published: December 2021

Cleavage Under Targets & Tagmentation (CUT&Tag) is an antibody-directed transposase tethering strategy for in situ chromatin profiling in small samples and single cells. We describe a modified CUT&Tag protocol using a mixture of an antibody to the initiation form of RNA Polymerase II (Pol2 Serine-5 phosphate) and an antibody to repressive Polycomb domains (H3K27me3) followed by computational signal deconvolution to produce high-resolution maps of both the active and repressive regulomes in single cells. The ability to seamlessly map active promoters, enhancers and repressive regulatory elements using a single workflow provides a complete regulome profiling strategy suitable for high-throughput single-cell platforms.
IL-23 signaling prevents ferroptosis-driven renal immunopathology during candidiasis
Authors: Millet Nicolas , Solis Norma V. , Aguilar Diane , Lionakis Michail S. , Wheeler Robert T. , Jendzjowsky Nicholas , Swidergall Marc
Published: December 2021

During infection the host relies on pattern-recognition receptors to sense invading fungal pathogens to launch immune defense mechanisms. While fungal recognition and immune effector responses are organ and cell type specific, during disseminated candidiasis myeloid cells exacerbate collateral tissue damage. However, the complex interplay between protective antifungal immunity and immunopathology remains incompletely understood. The β-glucan receptor ephrin type-A 2 receptor (EphA2) is required to initiate mucosal inflammatory responses during oralCandidainfection. Here we report that Epha2 promotes renal immunopathology during disseminated candidiasis. EphA2 deficiency leads to reduced renal inflammation and injury. Comprehensive analyses reveal that EphA2 limits IL-23 secretion in dendritic cells, while IL-23 signaling prevents ferroptotic myeloid cell death during infection. Further, ferroptosis aggravates inflammation during infection, while at the same time reducing the fungal killing capacity of macrophages. Thus, we identify ferroptotic cell death as a critical pathway ofCandida-mediated renal immunopathology that opens a new avenue to tackleCandidainfection and inflammation.
Scellseg: a style-aware cell instance segmentation tool with pre-training and contrastive fine-tuning
Authors: Xun Dejin , Chen Deheng , Zhou Yitian , Lauschke Volker M. , Wang Rui , Wang Yi
Published: December 2021

Deep learning-based cell segmentation is increasingly utilized in cell biology and molecular pathology, due to massive accumulation of diverse large-scale datasets and excellent progress in cell representation. However, the development of specialized algorithms has long been hampered by a paucity of annotated training data, whereas the performance of generalist algorithm was limited without experiment-specific calibration. Here, we present a deep learning-based tool called Scellseg consisted of novel pre-trained network architecture and contrastive fine-tuning strategy. In comparison to four commonly used algorithms, Scellseg outperformed others in average precision and Aggregated Jaccard Index on three disparate datasets. Interestingly, we found that eight images are sufficient for model tuning to achieve satisfied performance based on a shot data scale experiment. We also developed a graphical user interface integrated with functions of annotation, fine-tuning and inference, that allows biologists to easily specialize their self-adaptive segmentation model for analyzing images at the single-cell level.