bluuebunny/crossref_metadata_2025 huggingface dataset:
Adenosine monophosphate deaminase modulates BIN2 activity through hydrogen peroxide-induced oligomerization
Authors: Lu Qing , Houbaert Anaxi , Ma Qian , Huang Jingjing , Sterck Lieven , Zhang Cheng , Benjamins René , Coppens Frederik , Van Breusegem Frank , Russinova Eugenia
Published: July 2022

The Arabidopsis thaliana GSK3-like kinase, BRASSINOSTEROID-INSENSITIVE2 (BIN2) is a key negative regulator of brassinosteroid (BR) signaling and a hub for crosstalk with other signaling pathways. However, the mechanisms controlling BIN2 activity are not well understood. Here we performed a forward genetic screen for resistance to the plant-specific GSK3 inhibitor bikinin and discovered that a mutation in the ADENOSINE MONOPHOSPHATE DEAMINASE (AMPD)/EMBRYONIC FACTOR1 (FAC1) gene reduces the sensitivity of Arabidopsis seedlings to both bikinin and BRs. Further analyses revealed that AMPD modulates BIN2 activity by regulating its oligomerization in a hydrogen peroxide (H2O2)-dependent manner. Exogenous H2O2 induced the formation of BIN2 oligomers with a decreased kinase activity and an increased sensitivity to bikinin. By contrast, AMPD activity inhibition reduced the cytosolic reactive oxygen species (ROS) levels and the amount of BIN2 oligomers, correlating with the decreased sensitivity of Arabidopsis plants to bikinin and BRs. Furthermore, we showed that BIN2 phosphorylates AMPD to possibly alter its function. Our results uncover the existence of an H2O2 homeostasis-mediated regulation loop between AMPD and BIN2 that fine-tunes the BIN2 kinase activity to control plant growth and development.
GlutathioneS-transferase interactions enhance wheat resistance to powdery mildew but not wheat stripe rust
Authors: Wang Qiao , Guo Jia , Jin Pengfei , Guo Mengying , Guo Jun , Cheng Peng , Li Qiang , Wang Baotong
Published: July 2022

Wheat stripe rust and powdery mildew are important worldwide diseases of wheat (Triticum aestivum). The wheat cultivar Xingmin318 (XM318) is resistant to both wheat stripe rust and powdery mildew, which are caused by Puccinia striiformis f. sp. tritici (Pst) and Blumeria graminis f. sp. tritici (Bgt), respectively. To explore the difference between wheat defense response against Pst and Bgt, quantitative proteomic analyses of XM318 inoculated with either Pst or Bgt were performed using tandem mass tags technology. A total of 741 proteins were identified as differentially accumulated proteins (DAPs). Bioinformatics analyses indicated that some functional categories, including antioxidant activity and immune system process, exhibited obvious differences between Pst and Bgt infections. Intriguingly, only 42 DAPs responded to both Pst and Bgt infections. Twelve DAPs were randomly selected for reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis, and the mRNA expression levels of 11 were consistent with their protein expression. Furthermore, gene silencing using the virus-induced gene silencing system indicated that glutathione S-transferase (TaGSTU6) has an important role in resistance to Bgt but not to Pst. TaGSTU6 interacted with the cystathionine beta-synthase (CBS) domain-containing protein (TaCBSX3) in both Pst and Bgt infections. Knockdown of TaCBSX3 expression only reduced wheat resistance to Bgt infection. Overexpression of TaGSTU6 and TaCBSX3 in Arabidopsis (Arabidopsis thaliana) promoted plant resistance to Pseudomonas syringae pv. Tomato DC3000. Our results indicate that TaGSTU6 interaction with TaCBSX3 only confers wheat resistance to Bgt, suggesting that wheat has different response mechanisms to Pst and Bgt stress.
Altered properties and structures of root exudate polysaccharides in a root hairless mutant of barley
Authors: Galloway Andrew F , Akhtar Jumana , Burak Emma , Marcus Susan E , Field Katie J , Dodd Ian C , Knox Paul
Published: July 2022

Root exudates and rhizosheaths of attached soil are important features of growing roots. To elucidate factors involved in rhizosheath formation, wild-type (WT) barley (Hordeum vulgare L. cv. Pallas) and a root hairless mutant, bald root barley (brb), were investigated with a combination of physiological, biochemical, and immunochemical assays. When grown in soil, WT barley roots bound ∼5-fold more soil than brb per unit root length. High molecular weight (HMW) polysaccharide exudates of brb roots had less soil-binding capacity than those of WT root exudates. Carbohydrate and glycan monoclonal antibody analyses of HMW polysaccharide exudates indicated differing glycan profiles. Relative to WT plants, root exudates of brb had reduced signals for arabinogalactan-protein (AGP), extensin, and heteroxylan epitopes. In contrast, the root exudate of 2-week-old brb plants contained ∼25-fold more detectable xyloglucan epitope relative to WT. Root system immunoprints confirmed the higher levels of release of the xyloglucan epitope from brb root apices and root axes relative to WT. Epitope detection with anion-exchange chromatography indicated that the increased detection of xyloglucan in brb exudates was due to enhanced abundance of a neutral polymer. Conversely, brb root exudates contained decreased amounts of an acidic polymer, with soil-binding properties, containing the xyloglucan epitope and glycoprotein and heteroxylan epitopes relative to WT. We, therefore, propose that, in addition to physically structuring soil particles, root hairs facilitate rhizosheath formation by releasing a soil-binding polysaccharide complex.
Nowcasting Net Asset Values: The Case of Private Equity
Authors: Brown Gregory W , Ghysels Eric , Gredil Oleg R
Published: July 2022

We estimate unsmoothed private equity net asset values (NAVs) at weekly frequency for individual funds. Using simulations and large samples of buyout and venture funds, we show that our method yields superior estimates of NAVs relative to simple approaches based on extrapolation of reported NAVs. The market beta of an average buyout (venture) fund is around 1.0 (1.4), and the total risk is 33$\%$ (40$\%$) per year. The risk-return profile of the funds varies significantly over time and across funds. Risk-taking and reporting quality appear to persist by manager.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Post-INSURE Administration of Heated Humidified High-Flow Therapy Versus Nasal Continuous Positive Airway Pressure in Preterm Infants More Than 28 Weeks Gestation with Respiratory Distress Syndrome: A Randomized Non-Inferiority Trial
Authors: Singh Srijan , Ananthan Anitha , Nanavati Ruchi
Published: July 2022

In preterm infants with respiratory distress syndrome (RDS), non-invasive ventilation (NIV) is usually provided using nasal continuous positive airway pressure (NCPAP) or non-invasive mechanical ventilation after surfactant administration by INtubation-SURfactant-Extubation (INSURE) method. Heated humidified high-flow nasal cannula (HHHFNC) is a mode of NIV with advantages of ease of application, less grades of nasal injury and easy handling. This study was done to compare the effectiveness of HHHFNC therapy administration as post-INSURE respiratory support in preterm infants as compared to NCPAP. The primary outcome was to compare the rate of treatment failure within 7 days of randomization to HHHFNC or NCPAP as a post-INSURE ventilatory modality. It was a pilot trial wherein all preterm infants more than 1 kg and more than 28 weeks gestational age with RDS who required surfactant were randomized to receive NCPAP or HHHFNC. Infants with an urgent need for intubation and mechanical ventilation were considered to have treatment failure. Thirty babies were enrolled—15 in each group. Baseline demographic characteristics were comparable. There was no significant difference in the primary outcome of early failure rate, i.e. mechanical ventilation rate within 7 days of starting treatment. There were no significant differences in other outcomes except nasal injury which was significantly lesser in the HHHFNC group. In conclusion, HHHFNC appears to be non-inferior to NCPAP when used in preterm infants more than 28 weeks gestation with RDS as a post-INSURE ventilatory modality.
CHEST
Authors: El Hussein Mohamed Toufic , Habib Jenna
Published: July 2022

Acute pulmonary embolism is a challenging and potentially fatal disease that requires prompt assessment and precise management. Due to the lack of specific symptoms, NPs need to know how to identify a pulmonary embolism to manage it safely. This article discusses risk factors, initial approach, and diagnosis of acute pulmonary embolism using pretest probability and risk stratification tools. A mnemonic is proposed to guide medical management.
Atomised intranasal dexmedetomidine versus oral melatonin in prevention of emergence delirium in children undergoing ophthalmic surgery with sevoflurane
Authors: Jangra Savita , Ashok Vighnesh , Sethi Sameer , Ram Jagat
Published: July 2022

BACKGROUND

Melatonin and dexmedetomidine have both been used as a premedication to decrease emergence delirium in children. The effectiveness of oral melatonin, compared with atomised intranasal dexmedetomidine, in this role is not well studied.

OBJECTIVE

To study the efficacy of pre-operative atomised intranasal dexmedetomidine versus oral melatonin in children scheduled for ophthalmic surgery under sevoflurane.

DESIGN

A prospective, randomised, double-blind trial.

SETTING

Ophthalmic surgery in a university teaching hospital, April 2021 to October 2021.

PATIENTS

A total of 120 children undergoing ophthalmic surgery with sevoflurane anaesthesia.

INTERVENTION

Children were randomised to receive pre-operative intranasal dexmedetomidine 2 μ kg−1 via an atomiser device (dexmedetomidine group) or oral melatonin 0.5 mg kg−1 (melatonin group), 45 min before surgery.

OUTCOMES MEASURED

The primary outcome was the incidence of emergence delirium assessed by the Paediatric Anaesthesia Emergence Delirium scale. Secondary outcomes included pre-operative sedation, quality of inhalational induction, postoperative sedation and pain.

RESULTS

The incidence of emergence delirium was lower in the dexmedetomidine group than in the melatonin group (17 versus 37%, relative risk 0.45, 95% CI: 0.24 to 0.88; P = 0.01). Children in the dexmedetomidine group were more sedated following premedication and in the postanaesthesia care unit (P < 0.05). Postoperative pain scores were lower in the dexmedetomidine group than in the melatonin group: 0 [0 to 3] versus 2.5 [0–4], (P = 0.01). The requirement for and dose of rescue fentanyl analgesia postoperatively was comparable between the two groups.

CONCLUSION

Atomised intranasal dexmedetomidine significantly reduced emergence delirium in paediatric opthalmic procedures under sevoflurane anaesthesia compared to oral melatonin.

TRIAL REGISTRATION

Clinical Trials Registry of India CTRI/2021/03/032388 (www.ctri.nic.in)
Assessing individual patients’ knowledge of benign versus malignant skin lesions in the dermatology clinic population
Authors: Lee Kristin , Nguyen Ngoc , Fuzzell Meghan , Tung-Hahn Eleanor , Reserva Jeave , Balasubramanian Neelam , Tung Rebecca , Alam Murad , Stasko Thomas
Published: July 2022

Background:

Skin cancer education targeted to patients’ needs is a goal of practicing dermatologists. Data regarding dermatology patients’ baseline knowledge regarding skin cancer could aid clinicians in tailoring education efforts.

Objective:

To help quantify existing patients’ existing visual recognition of skin cancer and common benign lesions, with the goal of helping to provide more targeted and meaningful education to patients.

Methods:

Two hundred forty-four adult patients from the dermatology clinics at University of Oklahoma and Loyola University Chicago were surveyed using digital images and questions regarding personal and family history of skin cancer, sun protection practices and sun protection knowledge.

Results:

Of the 244 subjects, 43% percent had a positive personal history of skin cancer, 40% had a positive family history. Scores differed minimally by personal history of skin cancer (p = .37) but differed more markedly by family history of skin cancer (p = .02).

Limitations:

Lack of generalizability to the general public, age range of subjects.

Conclusions:

There are knowledge gaps within the dermatology patient population regarding common benign and malignant skin lesions.
Vitamin D Supplementation for Benign Paroxysmal Positional Vertigo: A Systematic Review
Authors: Hong Xinyuan , Christ-Franco Marina , Moher David , Tse Darren , Lelli Daniel A. , Schramm David , Caulley Lisa , Kontorinis Georgios
Published: July 2022

Objective

Benign paroxysmal positional vertigo (BPPV) is commonly attributed to displaced otoconia. These have been shown to have biomineralization close to that of bone, and vitamin D deficiency has been associated with BPPV. We aim to systematically review the available literature on vitamin D supplementation and BPPV intensity and recurrence in adults.

Databases Reviewed

PubMed, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Current Controlled Trials, and ClinicalTrials.gov.

Methods

We systematically reviewed the available literature from 1947 to April 2020. The study protocol was registered in the PROSPERO database (trial registration: CRD42020183195).

Results

A total of 179 abstracts were identified and screened by two independent reviewers. Based on inclusion and exclusion criteria, six studies were selected and subjected to a quality assessment. In one randomized clinical trial (RCT), vitamin D supplementation was found to reduce annual recurrence rate of vertigo in patient with BPPV and subnormal serum vitamin D levels compared with placebo (odds ratio, 0.69; 95% confidence interval, 0.54–0.90). Non-RCTs demonstrated the possibility of a null effect in the random effects model (odds ratio, 0.08; 95% confidence interval, 0.00–1.56). The RCT considered as low risk of bias. All of the nonrandomized studies were assessed as serious risk of bias.

Conclusions

The intervention studies identified consistently demonstrated a decrease in BPPV recurrence with supplementation of vitamin D in patients with subnormal vitamin D levels. Although there is a paucity of high-quality studies, the present literature does highlight a role for optimization of vitamin D levels in patients with BPPV.
“Post bariatric Abdominal Contouring; Technical approach and Quality of Life.”
Authors: El-Gharbawi Ahmed H. , El-Sabbagh Ahmed H. , Shouman Omar O. , El-Hadidy Mohamed R. , EL FAHAR Mohammed H.
Published: July 2022

Background:

Abdominal contouring is a very ubiquitous procedure after bariatric surgery that insufficient studies have measured grossly the outcome after it. In this study we aim to measure the surgical and functional outcomes after abdominal contouring in post-bariatric patients and their impact on life quality.

Methods:

Thirty post-bariatric patients, both males and females, of different age groups had undergone abdominal contouring through three procedures; traditional abdominoplasty, Fleur-de-lis abdominoplasty and belt lipectomy. The technical approach was decided according to each patient presentation regarding the amount and extent of skin redundancy. All patients were given a questionnaire booklet; a simplified question forms that assess different life quality and appearance scales, to fill out both before and 6 months after the procedure. Data were collected face to face at outpatient clinic during follow up, by e-mail or by messaging.

Results:

In this study, we have had conducted three different procedures; traditional abdominoplasty (7 cases), Fleur-de-lis abdominoplasty (8 cases) and belt lipectomy (15 cases). We found that the surgical outcomes (operative time, resection weight, blood transfusion, postoperative hemoglobin, postoperative albumin, hospital stay, drain period and complications) were influenced significantly by the procedure type (p ≤ 0.01). On the other hand, we found that the health-related QoL and appearance scales have changed significantly from the precontouring stage to the postcontouring stage, but this significant change in the functional outcome was not correlated to the technical approach.

Conclusion:

Abdominal contouring surgery improves the quality of life of post-bariatric patients irrespective of the procedure type and this gives evidence that those patients should have access to treatments.
A 20-year population-based study of all-cause and cause-specific mortality among people with concurrent HIV and psychotic disorders
Authors: Yazdani Kiana , Salters Kate , Shen Tian , Dolguikh Katerina , Trigg Jason , White Randall F. , Closson Kalysha , Nanditha Ni Gusti Ayu , Honer William G. , Vila-Rodriguez Fidel , Lima Viviane Dias , Montaner Julio S.G. , Barrios Rolando
Published: July 2022

Objective:

We aimed to characterize mortality among people with HIV (PWH) and psychotic disorders (PWH/psychosis+) vs. PWH alone (PWH/psychosis−).

Method:

A population-based analysis of mortality in PWH (age ≥19) in British Columbia (BC) from April 1996 to March 2017 was conducted using data from the Seek and Treat for Optimal Prevention of HIV/AIDS (STOP HIV/AIDS) study. Deaths were identified from the Vital Statistics Data (classified as HIV vs. non-HIV causes). Mortality trends across all fiscal years were examined. Cox models assessed the hazard of psychotic disorders on mortality; possible differences between schizophrenia and nonschizophrenia types of psychotic disorders were also evaluated.

Results:

Among 13 410 PWH included in the analysis, 1572 (11.7%) met the case definition for at least one psychotic disorder. Over the study period, 3274 deaths (PWH/psychosis−: n = 2785, PWH/psychosis+: n = 489) occurred. A decline over time in all-cause mortality and HIV-related mortality was observed in both PWH/psychosis+ and PWH/psychosis− (P value <0.0001). A decline in non-HIV mortality was observed among PWH/psychosis− (P value = 0.003), but not PWH/psychosis+ (P value = 0.3). Nonschizophrenia psychotic disorders were associated with increased risk of mortality; adjusted hazard ratios with (95% confidence intervals): all-cause 1.75 (1.46–2.09), HIV-related 2.08 (1.60–2.69), non-HIV-related 1.45 (1.11–1.90). Similar associations between schizophrenia and mortality were not observed.

Conclusion:

People with co-occurring HIV and nonschizophrenia psychotic disorders experienced a significantly higher risk of mortality vs. PWH without any psychotic disorder. Implementing care according to syndemic models considering interactions between HIV and particularly episodic psychotic disorders could help manage mortality risk more effectively among PWH/psychosis+.
Diet in a global cohort of adults with HIV at low-to-moderate traditional cardiovascular disease risk
Authors: Fitch Kathleen V. , McCallum Sara A. , Erlandson Kristine M. , Overton Edgar Turner , Zanni Markella V. , Fichtenbaum Carl , Aberg Judith A. , Fulda Evelynne S. , Kileel Emma M. , Moran Laura E. , Bloomfield Gerald S. , Novak Richard M. , Pérez-Frontera Sigrid , Abrams-Downey Alexandra , Pierone Gerald , Kumarasamy Nagalingeswaran , Ruxrungtham Kiat , Mngqibisa Rosie , Douglas Pamela S. , Ribaudo Heather J. , Grinspoon Steven K.
Published: July 2022

Objective:

To characterize diet quality across a global cohort of people with HIV (PWH).

Design:

Cross-sectional analysis.

Methods:

Leveraging REPRIEVE data from baseline across five Global Burden of Disease (GBD) regions, we analyzed participant responses to the Rapid Eating Assessment for Participants questionnaire. An overall diet quality score and scores for specific diet components were generated. Higher scores indicate better diet quality.

Results:

Among 7736 participants (median age 50 years, 30% women, median BMI 25.8 kg/m2) overall diet quality score (max score 30) was optimal in 13% of participants and good, suboptimal or poor in 45%, 38%, and 4% of participants, respectively; saturated fat score (max score 18) was good, suboptimal, or poor in 38%, 40%, or 7% of participants, respectively. Diet quality scores differed across GBD region with the highest scores reported in the South Asia region [median 23 (21–25)] and lowest in the sub-Saharan Africa region [median 15 (12–18)]; 61% of participants in the South Asia region reported optimal diet quality compared with only 6% in the sub-Saharan Africa region. Higher atherosclerotic cardiovascular risk scores were seen with worsening diet quality.

Conclusion:

Among PWH eligible for primary CVD prevention, diet quality was suboptimal or poor for almost half of participants, and there were substantial variations in diet quality reported by GBD region.

TRIAL REGISTRATION:

NCT02344290
Cranioplasty for Skull Defects With Polypropylene Abdominal Wall Mesh
Authors: Abuzayed Bashar , Rawagah Feras , Alrashdan Mohammad , Al-Abadi Husesein , Jamous Osama , Said Anas
Published: July 2022

Objective:

Cranioplasty is a well-established common surgery in the practice of neurosurgery and craniofacial surgery. In young patients, complete skull defect closure by bone splitting may be troublesome due to the difficulty to obtain enough bone area. In such cases, sometimes the authors need to use allografts, which may not be widely available in rural practice. In this study, the authors present the series of cranioplasty with polypropylene mesh, which is widely used in abdominal wall closure.

Patients and Methods:

Nine patients with depressed compound skull fracture were treated by performing this technique. Selection criteria were: compound depressed skull fractures in which bones were fragmented in a way not able to be reconstructed with and leaving a skull defect, small-sized or relatively medium-sized skull defects, and skull defects not located on the sharp curvatures of the skull which needs firm bended meshes. All patients were male and their ages ranged between 8 months and 36 years.

The skull bone defect was reconstructed with polypropylene abdominal wall mesh, which was sutured circumferentially with the galeal tissue.

Results:

Skull defects were successfully treated in all patients. The follow-up period ranged from 4 to 13 months. One patient with a history of alcoholism and neglectance developed a wound infection after 3 weeks of surgery. This patient was treated successfully with intravenous antibiotics without the need to remove the mesh. There were no complications in the remaining 8 patients.

Conclusions:

Polypropylene mesh is a cheap and effective material for the reconstruction of small-sized or medium-sized skull defects. It can be a good alternative in rural practice and/or low economic communities, when other cranioplasty materials are not available.
TIGIT-Fc Prolongs Corneal Allograft Survival in Mice by Upregulating TIGIT/CD226 Expression and the Proportion of Helios+Foxp3+ Treg Cells
Authors: Li Shang , Zhang Peng , Li Ao , Bao Jiayu , Pan Zhiqiang , Jie Ying
Published: July 2022

Background.

Reduction of graft rejection remains key issue for supporting long-term graft retention after corneal transplantation. The relevance of Treg in reduction of corneal allografts rejection has been demonstrated. It has been recently reported that in addition to Foxp3, Helios is also considered to be a marker of activated Treg. Helios+Foxp3+ Treg are considered to be the true immunosuppressive Treg. TIGIT is an immunosuppressive costimulatory molecule that was found to be highly expressed on the surface of Helios+Foxp3+ Treg.

Methods.

In this study, we aimed to explore whether supplementing TIGIT would result in an expansion and activation of Helios+Foxp3+ Treg thus to mediate an immune tolerance following corneal transplantation by administering topically and systemically TIGIT-Fc treatment in murine models.

Results.

TIGIT-Fc treatment significantly improved the survival of corneal allograft compared with the control group. TIGIT-Fc treatment increased TIGIT/CD226 expression, the proportion of Helios+Foxp3+ Treg cells and an enhanced ex vivo suppressive effect from peripheral lymph nodes isolated Treg cells. Furthermore, the expression of Helios in corneal grafts was upregulated, whereas expression of CD226 and production of aqueous interferon-γ and VEGF were reduced by TIGIT-Fc treatment.

Conclusions.

TIGIT-Fc treatment could specifically upregulate Helios+Foxp3+ Treg-mediated immune response after allogeneic corneal transplantation via TIGIT/CD226-CD155 pathway which improves the survival of allografts.
Visual bodily signals as core devices for coordinating minds in interaction
Authors: Holler Judith
Published: July 2022

The view put forward here is that visual bodily signals play a core role in human communication and the coordination of minds. Critically, this role goes far beyond referential and propositional meaning. The human communication system that we consider to be the explanandum in the evolution of language thus is not spoken language. It is, instead, a deeply multimodal, multilayered, multifunctional system that developed—and survived—owing to the extraordinary flexibility and adaptability that it endows us with. Beyond their undisputed iconic power, visual bodily signals (manual and head gestures, facial expressions, gaze, torso movements) fundamentally contribute to key pragmatic processes in modern human communication. This contribution becomes particularly evident with a focus that includes non-iconic manual signals, non-manual signals and signal combinations. Such a focus also needs to consider meaning encoded not just via iconic mappings, since kinematic modulations and interaction-bound meaning are additional properties equipping the body with striking pragmatic capacities. Some of these capacities, or its precursors, may have already been present in the last common ancestor we share with the great apes and may qualify as early versions of the components constituting the hypothesized interaction engine.

This article is part of the theme issue ‘Revisiting the human ‘interaction engine’: comparative approaches to social action coordination’.
Every product needs a process: unpacking joint commitment as a process across species
Authors: Bangerter Adrian , Genty Emilie , Heesen Raphaela , Rossano Federico , Zuberbühler Klaus
Published: July 2022

Joint commitment, the feeling of mutual obligation binding participants in a joint action, is typically conceptualized as arising by the expression and acceptance of a promise. This account limits the possibilities of investigating fledgling forms of joint commitment in actors linguistically less well-endowed than adult humans. The feeling of mutual obligation is one aspect of joint commitment (theproduct), which emerges from aprocessof signal exchange. It is gradual rather than binary; feelings of mutual obligation can vary in strength according to how explicit commitments are perceived to be. Joint commitment processes are more complex than simple promising, in at least three ways. They are affected by prior joint actions, which create precedents and conventions that can be embodied in material arrangements of institutions. Joint commitment processes also arise as solutions to generic coordination problems related to opening up, maintaining and closing down joint actions. Finally, during joint actions, additional, specific commitments are made piecemeal. These stack up over time and persist, making it difficult for participants to disengage from joint actions. These complexifications open up new perspectives for assessing joint commitment across species.

This article is part of the theme issue ‘Revisiting the human ‘interaction engine’: comparative approaches to social action coordination’.
Showing and giving: from incipient to conventional forms
Authors: Salter Gideon , Carpenter Malinda
Published: July 2022

Understanding humans' motivation and capacity for social interaction requires understanding communicative gestures. Gestures are one of the earliest means that infants employ to communicate with others, and showing and giving are among the earliest-emerging gestures. However, there are limited data on the processes that lead up to the emergence of conventional showing and giving gestures. This study aimed to provide such data. Twenty-five infants were assessed longitudinally at monthly intervals from 6 to 10 months of age using a variety of methods (elicitation procedures, free play observations and maternal interviews), as well as via questionnaires conducted at 11–12 months. A particular focus was on pre-conventional,
incipient gestures
, behaviours that involved some components of conventional gestures, but lacked other important components. We present observational evidence that at least some of these behaviours (observed as early as 7 months of age) were communicative and make the case for how conventional showing and giving may emerge gradually in the context of social interactions. We also discuss the influence of maternal interpretations of these early behaviours on their development. Overall, the study seeks to draw attention to the importance of understanding the cognitive, motor and interactional processes that lead to the emergence of infants’ earliest communicative gestures.

This article is part of the theme issue ‘Revisiting the human ‘interaction engine’: comparative approaches to social action coordination’.
Interaction and ostension: the myth of 4th-order intentionality
Authors: Sievers Christine
Published: July 2022

Research in comparative cognition on allegedly uniquely human capacities considers the identification of these human capacities in other species as one of their main points of inquiry. Capacities are applied in their theoretical descriptions to promising empirical data. The conclusion then often is that even though, on a behavioural level, the human and nonhuman cases appear related, on a cognitive level there is no relation whatsoever because the underlying cognitive states diverge in quality. This result seems dissatisfying for two reasons: (1) there is ample empirical evidence that suggests the presence of the capacities in other species, and (2) the claim that the underlying states diverge often hinges on the reference to the theoretical definitions of these capacities only. This opinion piece focuses on the capacity of ostensive intentional communication to demonstrate that the original theoretical analyses often are not befitting a comparative endeavour and should therefore not be used as pivotal reference within comparative research. An outlook will be provided on more promising approaches to identifying ostensive communication, namely an interactive approach that will allow for ostension to not be perceived as a one-turn signalling behaviour, but as interactive, with the possibility of being established in a trial-and-error manner.

This article is part of the theme issue ‘Revisiting the human ‘interaction engine’: comparative approaches to social action coordination’.
Coordinating social action: a primer for the cross-species investigation of communicative repair
Authors: Heesen Raphaela , Fröhlich Marlen , Sievers Christine , Woensdregt Marieke , Dingemanse Mark
Published: July 2022

Human joint action is inherently cooperative, manifested in the collaborative efforts of participants to minimize communicative trouble through interactive repair. Although interactive repair requires sophisticated cognitive abilities, it can be dissected into basic building blocks shared with non-human animal species. A review of the primate literature shows that interactionally contingent signal sequences are at least common among species of non-human great apes, suggesting a gradual evolution of repair. To pioneer a cross-species assessment of repair this paper aims at (i) identifying necessary precursors of human interactive repair; (ii) proposing a coding framework for its comparative study in humans and non-human species; and (iii) using this framework to analyse examples of interactions of humans (adults/children) and non-human great apes. We hope this paper will serve as a primer for cross-species comparisons of communicative breakdowns and how they are repaired.

This article is part of the theme issue ‘Revisiting the human ‘interaction engine’: comparative approaches to social action coordination’.
Using Real-Time Machine Learning to Prevent In-Hospital Severe Hypoglycemia: A prospective study
Authors: Fralick Michael , Debnath Meggie , Pou-Prom Chloe , O’Brien Patrick , Perkins Bruce A. , Carson Esmerelda , Khemani Fatima , Mamdani Muhammad
Published: July 2022

Objective

There are many examples of machine learning based algorithms with impressive diagnostic characteristics. However, a few published studies have evaluated how well they perform when deployed into clinical care. The objective of this study was to evaluate the performance of a recently validated machine-learned model to predict inpatient hypoglycemia following its implementation into clinical care on cardiovascular and vascular surgery ward.

Methods

We conducted a prospective analysis of a machine learning algorithm to predict hypoglycemia. The algorithm was trained, validated, and tested using data from 2013 to 2019. We employed multiple supervised machine learning techniques (e.g., extreme gradient boosting) to predict inpatient hypoglycemia and severe hypoglycemia using a wide-range of patient-level data (i.e., features) including medications, labs, nursing notes, comorbid conditions, among others.

Results

Our study included 3989 hospitalizations during the pre-implementation period and 1916 post-implementation. Approximately one-third of patients were women, the median age was 66 years, 23% received metformin in hospital, 7% received a sulfonylurea, and the median length of stay was 6 days. During the pre-implementation period, more than 5% of patients experienced hypoglycemia during 9.4% (N=12/127 weeks) of study weeks as compared to 0% (N=0/79 weeks) of weeks during the post-implementation period (p=0.012). The weekly variability in the rates of hypoglycemia decreased by approximately 50% from the pre-implementation (standard deviation 1.8, variance 3.4) to implementation phase (standard deviation 1.3, variance 1.6; p=0.03). There was a week-to-week decrease in hypoglycemia rates by 0.03 events per week [95% CI: -0.04, -0.01] (p = 0.004) but no significant change in weekly rates of hyperglycemia (−0.04 [95% CI: -0.10, 0.01]; p=0.102). The severe hypoglycemia events per 100 patients per year was 1.3 pre-implementation and 1.1 following implementation.

Discussion and Conclusion

Our prospective analysis of a recently validated machine learned model to prevent hypoglycemia demonstrated a reduction in the rates of inpatient hypoglycemia. Our study suggests that machine learning methods can be leveraged to prevent inpatient hypoglycemia.
Genetic variability, including gene duplication and deletion, in early sequences from the 2022 European monkeypox outbreak
Authors: Jones Terry C. , Schneider Julia , Mühlemann Barbara , Veith Talitha , Beheim-Schwarzbach Jörn , Tesch Julia , Schmidt Marie Luisa , Walper Felix , Bleicker Tobias , Isner Caroline , Pfäfflin Frieder , Werner Ricardo Niklas , Corman Victor M. , Drosten Christian
Published: July 2022

Genome sequences from 47 monkeypox virus infections detected in a German university virology laboratory were analyzed in context of other sequences from the 2022 outbreak and earlier monkeypox genomes. Identical non-synonymous amino acid changes in six genes and the signature of APOBEC editing match other sequences from the European outbreak. Non-synonymous changes that were present in one to three sequences were found in 34 other genes. In sequences from two lesions of one patient, an 856 nucleotide translocation between genome termini resulted in the duplication of an initial 5’ gene, and the disruption or complete deletion of four genes near the 3’ genome end. Orthopoxvirus genome rearrangements of this nature are known to confer fitness advantages in the face of selection pressure. This change may therefore represent an early virus adaptation in the novel widespread and sustained human-to-human context of the current monkeypox outbreak.
Plastid phylogenomics clarifies broad-level relationships inBulbophyllum(Orchidaceae) and provides insights into range evolution of Australasian sectionAdelopetalum
Authors: Simpson Lalita , Clements Mark A. , Orel Harvey K. , Crayn Darren M. , Nargar Katharina
Published: July 2022

The hyper diverse orchid genusBulbophyllumis the second largest genus of flowering plants and exhibits a pantropical distribution with a center of diversity in tropical Asia. The onlyBulbophyllumsection with a center of diversity in Australasia is sect.Adelopetalum. However, phylogenetic placement, interspecific relationships, and spatio-temporal evolution of the section have remained largely unclear. To infer broad-level relationships withinBulbophyllumand interspecific relationships within sect.Adelopetalum, a genome skimming dataset was generated for 89 samples, yielding 70 plastid coding regions and the nuclear ribosomal DNA cistron. For 18 additional samples, Sanger data from two plastid loci (matK,ycf1) and nuclear ITS were added using a supermatrix approach. The study provided new insights into broad-level relationships inBulbophyllum, including phylogenetic evidence for the non-monophyly of sectionsBeccariana, Brachyantha, Brachypus, Cirrhopetaloides, Cirrhopetalum, Desmosanthes, Minutissima, Oxysepala, PolymeresandSestochilos. SectionAdelopetalumand sect.Minutissima s.s. formed a highly supported clade that was resolved in sister group position to the remainder of the genus. Divergence time estimations based on a relaxed molecular clock model placed the origin ofBulbophyllumin the early Oligocene (ca. 33.2 Ma) and of sect.Adelopetalumin the late Oligocene (ca. 23.6 Ma). Ancestral range estimations based on a BAYAREALIKE model identified the Australian continent as ancestral area of sect.Adelopetalum. The section underwent crown diversification during the mid-Miocene to the late Pleistocene, predominantly in continental Australia. At least two independent long-distance dispersal events were inferred eastwards from the Australian continent to New Zealand, and New Caledonia from the early Pliocene onwards, likely mediated by the predominantly westerly winds of the southern hemisphere. Retraction and fragmentation of eastern Australian rainforests from the early Miocene onwards are discussed as likely drivers of lineage divergence within sect.Adelopetalum, facilitating allopatric speciation.
Expansion of the Catalytic Repertoire of Alcohol Dehydrogenases in Plant Metabolism
Authors: Langley Chloe , Tatsis Evangelos , Hong Benke , Nakamura Yoko , Paetz Christian , Stevenson Clare E. M. , Basquin Jerome , Lawson David M. , Caputi Lorenzo , O’Connor Sarah E.
Published: July 2022

Medium-chain alcohol dehydrogenases (ADHs) comprise a highly conserved enzyme family that catalyse the reversible reduction of aldehydes. However, recent discoveries in plant natural product biosynthesis suggest that the catalytic repertoire of ADHs has been expanded. Here we report the crystal structure of dihydroprecondylocarpine acetate synthase (DPAS), an ADH that catalyses the non-canonical 1,4 reduction of an α,β-unsaturated iminium moiety. Comparison with structures of plant-derived ADHs that catalyse 1,2-aldehyde and 1,2-iminium reductions suggest how the canonical ADH active site can be modified to carry out atypical carbonyl reductions, providing insight into how chemical reactions are diversified in plant metabolism.
From vacuole to cytosol – Disruptive invasion triggers cytosolic release ofSalmonellaParatyphi A and subsequent cytosolic motility favors evasion of xenophagy
Authors: Scharte Felix , Franzkoch Rico , Hensel Michael
Published: July 2022

Salmonella entericais a common foodborne, facultative intracellular enteropathogen. TyphoidalS.entericaserovars like Paratyphi A (SPA) are human restricted and cause a severe systemic disease, while manyS.entericaserovars like Typhimurium (STM) have broad host range, and in human hosts usually lead to self-limiting gastroenteritis. There are key differences between typhoidal and non-typhoidalSalmonellain pathogenesis, but underlying mechanisms remain largely unknown. Several genes encodingSalmonellapathogenicity island (SPI) effector proteins are absent or pseudogenes in SPA. Expression of virulence and metabolism genes show differential expression compared to STM. The intracellular transcriptomic architecture and phenotypes during presence in epithelial cells were recently described. Surprisingly, induction of motility, flagella and chemotaxis genes showed distinct expression patterns in intracellular SPA vs. STM and led to cytosolic motility of SPA. This study applies single cell microscopic analyses approaches to investigate the triggers and cellular consequences of cytosolic motility. Live cell imaging (LCI) revealed that SPA invades host cells in a highly cooperative manner. Extensive membrane ruffling at the invasion site leads to increased membrane damage in the nascent SCV with subsequent cytosolic release. After release into the cytosol, motile bacteria showed same velocity as under culture conditions used for infection. Reduced capture of SPA by autophagosomal membranes was observed by LCI and electron microscopy. Our results reveal flagella-mediated cytosolic motility as possible xenophagy evasion mechanism that could drive disease progression and contributes to dissemination of invasion-primed SPA during systemic infection.

Importance

Intracellular pathogens are commonly adapted to life in host cells either in a pathogen-containing vacuole, or free in host cell cytosol. However, transitions between these lifestyles are possible and demand specific adaptations, especially to avoid recognition and killing by host cell-autonomous immune defense.Salmonella entericaserovar Paratyphi A (SPA) belongs to typhoidalSalmonellaable to cause live-threatening systemic infections in human hosts. We observed that SPA invades host cells in a way that often results in damage of the nascent vacuole and release of SPA in host cell cytosol. Here, SPA deploy flagella-mediated motility for rapid locomotion within infected cells. We demonstrate on single cell level that flagella-mediated motility enables evasion of xenophagic capture and control by the host cells. SPA uses a novel form of intracellular motility to successfully colonize human host cells.
Structural basis of a high-affinity antibody binding to glycoprotein region with consecutive glycosylation sites
Authors: Han Yunbin , Niu Jun , Pan Deng , Feng Chunchao , Song Ke , Meng Bing , Westerlind Ulrika , Zhang Yan , Liu Haiguang , Xu Lan , Zhou Dapeng
Published: July 2022

Consecutive glycosylation sites occur in both self and viral proteins. Glycan-shielding of underneath peptide region is a double-edged sword, that avoids immune attack to self-proteins, but helps viruses including HIV-1 and SARS-CoV2 to escape antibody binding. Here we report a high-affinity antibody, 16A, binding to linear peptide containing consecutive glycosylation sites. Co-crystallization of 16A Fab and glycopeptides with GalNAc modifications at different sites showed that STAPPAHG is the sequence recognized by 16A antibody. GalNAc modification at Threonine site on STAPPAHG sequence significantly increased the affinity of Fab binding by 30.6 fold (KD=6.7nM). The increased affinity is conferred by hydrophilic and pi-stacking interactions between the GalNAc residue on Threonine site and a Trp residue from the CDR1 region of the heavy chain. Furthermore, molecular modeling suggested that GalNAc on T site causes more favorable conformation for antibody binding. These results showed that glycan modification most proximal to linear peptide core epitope significantly increases antigenicity of a glycopeptide epitope. The antibody recognition mode by peptide-binding CDR groove with a glycan-binding edge, may shed light on designing of linear glycopeptide-based vaccines for cancer and viral diseases.

Teaser

A high-affinity antibody was found to bind densely glycosylated glycoprotein region by a peptide binding groove of the antibody’s variant region, with a glycan-binding edge specific to glycosylation site most proximal to core peptide epitope.
Irradiated Mammary Spheroids Elucidate Mechanisms of Macrophage-Mediated Breast Cancer Recurrence
Authors: Hacker Benjamin C. , Lin Erica J. , Herman Dana C. , Questell Alyssa M. , Martello Shannon E. , Hedges Rebecca J. , Walker Anesha J. , Rafat Marjan
Published: July 2022

While most patients with triple negative breast cancer receive radiotherapy to improve outcomes, a significant subset of patients continue to experience recurrence. Macrophage infiltration into radiation-damaged sites has been shown to promote breast cancer recurrence in pre-clinical models. However, the mechanisms that drive recurrence are unknown. Here, we developed a novel spheroid model to evaluate macrophage-mediated tumor cell recruitment. We first characterized infiltrating macrophage phenotypes into irradiated mammary tissue to inform our model. We then established spheroids consisting of fibroblasts isolated from mouse mammary glands. We observed that tumor cell motility toward irradiated spheroids was enhanced in the presence of a 2:1 ratio of pro-healing:pro-inflammatory macrophages. We also measured a significant increase in interleukin 6 (IL-6) secretion after irradiation bothin vivoand in our model. This secretion increased tumor cell invasiveness, and invasion was mitigated by neutralizing IL-6. Taken together, our work suggests that interactions between infiltrating macrophages and damaged stromal cells facilitates breast cancer recurrence through IL-6 signaling.
Multi-Omics Binary Integration via Lasso Ensembles (MOBILE) for identification of context-specific networks and new regulatory mechanisms
Authors: Erdem Cemal , Gross Sean M. , Heiser Laura M. , Birtwistle Marc R.
Published: July 2022

Cell phenotypes are dictated by both extra- and intra-cellular contexts, and robust identification of context-specific network features that control phenotypes remains challenging. Here, we developed a multi-omics data integration strategy called MOBILE (Multi-Omics Binary Integration via Lasso Ensembles) to nominate molecular features associated with specific cellular phenotypes. We applied this method to chromatin accessibility, mRNA, protein, and phospho-protein time course datasets and focus on two illustrative use cases after we show MOBILE could recover known biology. First, MOBILE nominated new mechanisms of interferon-γ (IFNγ) regulated PD-L1 expression, where analyses suggested, and literature supported that IFNγ-controlled PD-L1 expression involves BST2, CLIC2, FAM83D, ACSL5, and HIST2H2AA3 genes. Second, we explored differences between the highly similar transforming growth factor-beta 1 (TGFβ1) and bone morphogenetic protein 2 (BMP2) and showed that differential cell size and clustering properties induced by TGFβ1, but not BMP2, were related to the laminin/collagen pathway activity. Given the ever-growing availability of multi-omics datasets, we envision that MOBILE will be broadly applicable to identify context-specific molecular features associated with cellular phenotypes.

Graphical Summary

Multi-Omics Binary Integration via Lasso Ensembles (MOBILE) pipeline yields statistically robust, context-specific association networks

The MOBILE pipeline integrates omics datasets in a data-driven, biologically-structured manner.

The pipeline outputs are gene-level, contextspecific association networks.

These association networks nominate differentially enriched pathways, subnetworks, and new connections.

Broadly applicable to find condition specific networks using multi-omics datasets.