bluuebunny/crossref_metadata_2025 huggingface dataset:
Retrospective evaluation of carboxyhemoglobin and methemoglobin levels in dogs and cats with respiratory disease
Authors: Wolf Jacob M. , Hess Rebecka S. , Hering Caitlin T. , Silverstein Deborah C.
Published: April 2022

Objective

To evaluate carboxyhemoglobin (COHb) and methemoglobin (MetHb) levels in dogs and cats with respiratory disease in the ICU.

Design

Retrospective study.

Setting

University veterinary teaching hospital.

Animals

The ICU census was searched for dogs (n = 466) and cats (n = 97) hospitalized within the ICU between January 2016 and January 2019 in whom blood gas with co‐oximetry was performed. Dogs and cats were stratified into those with primary respiratory and nonrespiratory categories; the underlying cause of the disease was also noted. Venous blood gas, co‐oximeter, PaO2/FiO2 (PF ratio), physical examination findings, and outcome were recorded.

Measurements and main results

The median COHb and MetHb in dogs hospitalized in the ICU were 2.6% (0.1%–5.6%) and 1.1% (0.1%–2.9%), respectively. The median COHb and MetHb in cats hospitalized in the ICU were 2.2% (0.1%–5.4%) and 1.0% (0%–2.1%), respectively. Dogs with respiratory disease had a higher COHb than dogs without respiratory disease (median, 2.7% [range, 0.3%–5.0%] vs. 2.5% [0.1%–5.6%]; P = 0.0148). COHb was positively associated with survival in cats (median, 2.2% [range, 0.1%–5.4%] vs. 1.9% [0.1%–3.9%]; P = 0.0433). Both COHb and MetHb were higher in septic dogs than in nonseptic dogs (median COHb, 2.8% [range 0.3%–4.5%] vs. 2.6% [0.1%–5.6%]; P = 0.02 and median MetHb, 1.1% [0.1%–2.9%] vs. 1.1% [0.1%–2.4%]; P = 0.01, respectively).

Conclusions

There may be a positive association between COHb and respiratory disease in dogs; prospective studies are needed to evaluate this further. No association between COHb and respiratory disease in cats or MetHb and respiratory disease in either species was detected. Additional prospective studies are needed to determine whether COHb and MetHb are biomarkers for sepsis in dogs and whether COHb is an indicator of mortality in cats.
VARIOUS REGULATIONS ON THE EXISTENCE OF N-TH ORDER LIMIT LANGUAGE
Authors: Mohd Khairuddin Siti Hajar , Ahmad Muhammad Azrin , Adzhar Noraziah
Published: April 2022

In molecular biology, recombinant Deoxyribonucleic acid technology has ignited an increase in the interest of new researches. Moreover, the splicing system has generated enthusiasm in developing computational models collaborating with formal language theory. Formal language theory tends to be a natural structure for formalising and investigating DNA computing models from this viewpoint. The work of several researchers who added control structures to the splicing formalism, thus creating universal computation systems, has provided additional inspiration for the study of splicing systems. A splicing system is a conventional model of a set of dsDNA that undergoes the cutting and pasting process with the presence of restriction enzyme and ligase. Previously, an introduction of the n-th order limit language is presented and discussed. The properties and the characteristics of the n-th order limit language are developed and also explained by using examples and sort into a few cases. However, the regulation of the existence of the n-th order limit language is left unintended. In this paper, the factors that restrict the formation of the n-th order limit language are discussed. Several restrictions applied are the length of the rules are not equal and same rules applies on several crossing sites of the initial strings. In addition, some examples are given to show the restriction of the formation of n-order limit language.
RESEARCH PROGRESS ON MICROBIAL SELF-HEALING CONCRETE
Authors: Yip Bao Fang , Mohd Haniffah Mohd Ridza , Kasiman Erwan Hafizi , Zainal Abidin Ahmad Razin
Published: April 2022

Crack formation in concrete is inevitable. The cracks allow the penetration of harmful substances which may decrease the durability and the service life of concrete structures. Self-healing concrete is therefore emerging as an innovative construction material to tackle the cracking issues. In recent years, microbial self-healing concrete is garnering interest from many researchers due to its environmentally-friendly nature and the concrete compatibility of microbially-induced calcium carbonate precipitation. Various metabolic mechanisms have been used for microbial self-healing concrete production and urea hydrolysis is the most preferable metabolic pathway due to its fast and high precipitation of calcium carbonate. In this paper, a comprehensive review on the research progress on microbial self-healing concrete is presented together with the numerical modelling of microbial self-healing concrete. The challenges and limitations of microbial self-healing concrete are discussed along with the recommendations for its prospective uses in the construction industry. It is found that the survival of bacteria through direct addition technique is limited and needs further investigation. The immobilization technique gives a promising result in durability properties but doesn’t reach the mechanical requirement. Moreover, a comprehensive assessment of self-healing efficiency is required, and more efforts are needed to improve from laboratory scale to large-scaled application.
Estimation of sibilant groove formation and sound generation from early hominin jawbones
Authors: Yoshinaga Tsukasa , Nozaki Kazunori , Kondo Osamu , Iida Akiyoshi
Published: April 2022

The speech production capability of sibilant fricatives of early hominin was assessed by interpolating the modern human vocal tract to an Australopithecine specimen based on the jawbone landmarks, and then simulating the airflow and sound generation. The landmark interpolation demonstrates the possibility to form the sibilant groove in the anterior part of the oral tract, and results of the aeroacoustic simulation indicate that the early hominins had the potential to produce the fricative broadband noise with a constant supply of airflow to the oral cavity, although the ancestor's tongue deformation ability is still uncertain, and the results are highly speculative.
Simultaneous monitoring of disease and microbe dynamics through plasma DNA sequencing in pediatric patients with acute lymphoblastic leukemia
Authors: Barsan Valentin , Xia Yuntao , Klein David , Gonzalez-Pena Veronica , Youssef Sarah , Inaba Yuki , Mahmud Ousman , Natarajan Sivaraman , Agarwal Vibhu , Pang Yakun , Autry Robert , Pui Ching-Hon , Inaba Hiroto , Evans William , Gawad Charles
Published: April 2022

Treatment of acute lymphoblastic leukemia (ALL) necessitates continuous risk assessment of leukemic disease burden and infections that arise in the setting of immunosuppression. This study was performed to assess the feasibility of a hybrid capture next-generation sequencing panel to longitudinally measure molecular leukemic disease clearance and microbial species abundance in 20 pediatric patients with ALL throughout induction chemotherapy. This proof of concept helps establish a technical and conceptual framework that we anticipate will be expanded and applied to additional patients with leukemia, as well as extended to additional cancer types. Molecular monitoring can help accelerate the attainment of insights into the temporal biology of host-microbe-leukemia interactions, including how those changes correlate with and alter anticancer therapy efficacy. We also anticipate that fewer invasive bone marrow examinations will be required, as these methods improve with standardization and are validated for clinical use.
Higher-dimensional neural representations predict better episodic memory
Authors: Sheng Jintao , Zhang Liang , Liu Chuqi , Liu Jing , Feng Junjiao , Zhou Yu , Hu Huinan , Xue Gui
Published: April 2022

Episodic memory enables humans to encode and later vividly retrieve information about our rich experiences, yet the neural representations that support this mental capacity are poorly understood. Using a large fMRI dataset (
n
= 468) of face-name associative memory tasks and principal component analysis to examine neural representational dimensionality (RD), we found that the human brain maintained a high-dimensional representation of faces through hierarchical representation within and beyond the face-selective regions. Critically, greater RD was associated with better subsequent memory performance both within and across participants, and this association was specific to episodic memory but not general cognitive abilities. Furthermore, the frontoparietal activities could suppress the shared low-dimensional fluctuations and reduce the correlations of local neural responses, resulting in greater RD. RD was not associated with the degree of item-specific pattern similarity, and it made complementary contributions to episodic memory. These results provide a mechanistic understanding of the role of RD in supporting accurate episodic memory.
Portable, low-field magnetic resonance imaging enables highly accessible and dynamic bedside evaluation of ischemic stroke
Authors: Yuen Matthew M. , Prabhat Anjali M. , Mazurek Mercy H. , Chavva Isha R. , Crawford Anna , Cahn Bradley A. , Beekman Rachel , Kim Jennifer A. , Gobeske Kevin T. , Petersen Nils H. , Falcone Guido J. , Gilmore Emily J. , Hwang David Y. , Jasne Adam S. , Amin Hardik , Sharma Richa , Matouk Charles , Ward Adrienne , Schindler Joseph , Sansing Lauren , de Havenon Adam , Aydin Ani , Wira Charles , Sze Gordon , Rosen Matthew S. , Kimberly W. Taylor , Sheth Kevin N.
Published: April 2022

Brain imaging is essential to the clinical management of patients with ischemic stroke. Timely and accessible neuroimaging, however, can be limited in clinical stroke pathways. Here, portable magnetic resonance imaging (pMRI) acquired at very low magnetic field strength (0.064 T) is used to obtain actionable bedside neuroimaging for 50 confirmed patients with ischemic stroke. Low-field pMRI detected infarcts in 45 (90%) patients across cortical, subcortical, and cerebellar structures. Lesions as small as 4 mm were captured. Infarcts appeared as hyperintense regions on T2-weighted, fluid-attenuated inversion recovery and diffusion-weighted imaging sequences. Stroke volume measurements were consistent across pMRI sequences and between low-field pMRI and conventional high-field MRI studies. Low-field pMRI stroke volumes significantly correlated with stroke severity and functional outcome at discharge. These results validate the use of low-field pMRI to obtain clinically useful imaging of stroke, setting the stage for use in resource-limited environments.
A somatic mutation in moesin drives progression into acute myeloid leukemia
Authors: Yuan Ouyang , Ugale Amol , de Marchi Tommaso , Anthonydhason Vimala , Konturek-Ciesla Anna , Wan Haixia , Eldeeb Mohamed , Drabe Caroline , Jassinskaja Maria , Hansson Jenny , Hidalgo Isabel , Velasco-Hernandez Talia , Cammenga Jörg , Magee Jeffrey A. , Niméus Emma , Bryder David
Published: April 2022

Acute myeloid leukemia (AML) arises when leukemia-initiating cells, defined by a primary genetic lesion, acquire subsequent molecular changes whose cumulative effects bypass tumor suppression. The changes that underlie AML pathogenesis not only provide insights into the biology of transformation but also reveal novel therapeutic opportunities. However, backtracking these events in transformed human AML samples is challenging, if at all possible. Here, we approached this question using a murine in vivo model with an MLL-ENL fusion protein as a primary molecular event. Upon clonal transformation, we identified and extensively verified a recurrent codon-changing mutation (Arg
295
Cys) in the ERM protein moesin that markedly accelerated leukemogenesis. Human cancer-associated moesin mutations at the conserved arginine-295 residue similarly enhanced MLL-ENL–driven leukemogenesis. Mechanistically, the mutation interrupted the stability of moesin and conferred a neomorphic activity to the protein, which converged on enhanced extracellular signal–regulated kinase activity. Thereby, our studies demonstrate a critical role of ERM proteins in AML, with implications also for human cancer.
Detection of stroke by portable, low-field MRI: A milestone in medical imaging
Authors: Basser Peter
Published: April 2022

Portable, low-field magnetic resonance imagers can aid the clinical assessment of stroke. They may also help democratize access to scarce medical imaging resources.
Toward more streamlined testing in pediatric oncology
Authors: Walsh Michael F.
Published: April 2022

Gene sequencing of blood plasma simultaneously detects cancer and infectious disease in pediatric leukemia patients.
Exploring planet geology through force-feedback telemanipulation from orbit
Authors: Panzirsch Michael , Pereira Aaron , Singh Harsimran , Weber Bernhard , Ferreira Edmundo , Gherghescu Andrei , Hann Lukas , den Exter Emiel , van der Hulst Frank , Gerdes Levin , Cencetti Leonardo , Wormnes Kjetil , Grenouilleau Jessica , Carey William , Balachandran Ribin , Hulin Thomas , Ott Christian , Leidner Daniel , Albu-Schäffer Alin , Lii Neal Y. , Krüger Thomas
Published: April 2022

Current space exploration roadmaps envision exploring the surface geology of celestial bodies with robots for both scientific research and in situ resource utilization. In such unstructured, poorly lit, complex, and remote environments, automation is not always possible, and some tasks, such as geological sampling, require direct teleoperation aided by force-feedback (FF). The operator would be on an orbiting spacecraft, and poor bandwidth, high latency, and packet loss from orbit to ground mean that safe, stable, and transparent interaction is a substantial technical challenge. For this scenario, a control method was developed that ensures stability at high delay without reduction in speed or loss of positioning accuracy. At the same time, a new level of safety is achieved not only through FF itself but also through an intrinsic property of the approach preventing hard impacts. On the basis of this method, a tele-exploration scenario was simulated in the Analog-1 experiment with an astronaut on the International Space Station (ISS) using a 6–degree-of-freedom (DoF) FF capable haptic input device to control a mobile robot with manipulator on Earth to collect rock samples. The 6-DoF FF telemanipulation from space was performed at a round-trip communication delay constantly between 770 and 850 milliseconds and an average packet loss of 1.27%. This experiment showcases the feasibility of a complete space exploration scenario via haptic telemanipulation under spaceflight conditions. The results underline the benefits of this control method for safe and accurate interactions and of haptic feedback in general.
Cooperative cargo transportation by a swarm of molecular machines
Authors: Akter M. , Keya J. J. , Kayano K. , Kabir A. M. R. , Inoue D. , Hess H. , Sada K. , Kuzuya A. , Asanuma H. , Kakugo A.
Published: April 2022

Cooperation is a strategy that has been adopted by groups of organisms to execute complex tasks more efficiently than single entities. Cooperation increases the robustness and flexibility of the working groups and permits sharing of the workload among individuals. However, the utilization of this strategy in artificial systems at the molecular level, which could enable substantial advances in microrobotics and nanotechnology, remains highly challenging. Here, we demonstrate molecular transportation through the cooperative action of a large number of artificial molecular machines, photoresponsive DNA-conjugated microtubules driven by kinesin motor proteins. Mechanical communication via conjugated photoresponsive DNA enables these microtubules to organize into groups upon photoirradiation. The groups of transporters load and transport cargo, and cargo unloading is achieved by dissociating the groups into single microtubules. The group formation permits the loading and transport of cargoes with larger sizes and in larger numbers over long distances compared with single transporters. We also demonstrate that cargo can be collected at user-determined locations defined by ultraviolet light exposure. This work demonstrates cooperative task performance by molecular machines, which will help to construct molecular robots with advanced functionalities in the future.
Steroid-induced fibroblast growth factors drive an epithelial-mesenchymal inflammatory axis in severe asthma
Authors: Guidi Riccardo , Xu Daqi , Choy David F. , Ramalingam Thirumalai R. , Lee Wyne P. , Modrusan Zora , Liang Yuxin , Marsters Scot , Ashkenazi Avi , Huynh Alison , Mills Jessica , Flanagan Sean , Hambro Shannon , Nunez Victor , Leong Laurie , Cook Ashley , Tran Tiffany Hao , Austin Cary D. , Cao Yi , Clarke Christine , Panettieri Reynold A. , Koziol-White Cynthia , Jester William F. , Wang Fen , Wilson Mark S.
Published: April 2022

Asthma and inflammatory airway diseases restrict airflow in the lung, compromising gas exchange and lung function. Inhaled corticosteroids (ICSs) can reduce inflammation, control symptoms, and improve lung function; however, a growing number of patients with severe asthma do not benefit from ICS. Using bronchial airway epithelial brushings from patients with severe asthma or primary human cells, we delineated a corticosteroid-driven fibroblast growth factor (FGF)–dependent inflammatory axis, with FGF-responsive fibroblasts promoting downstream granulocyte colony-stimulating factor (G-CSF) production, hyaluronan secretion, and neutrophilic inflammation. Allergen challenge studies in mice demonstrate that the ICS, fluticasone propionate, inhibited type 2–driven eosinophilia but induced a concomitant increase in FGFs, G-CSF, hyaluronan, and neutrophil infiltration. We developed a model of steroid-induced neutrophilic inflammation mediated, in part, by induction of an FGF-dependent epithelial-mesenchymal axis, which may explain why some individuals do not benefit from ICS. In further proof-of-concept experiments, we found that combination therapy with pan-FGF receptor inhibitors and corticosteroids prevented both eosinophilic and steroid-induced neutrophilic inflammation. Together, these results establish FGFs as therapeutic targets for severe asthma patients who do not benefit from ICS.
Porcine Epidemic Diarrhea Virus nsp7 Inhibits Interferon-Induced JAK-STAT Signaling through Sequestering the Interaction between KPNA1 and STAT1
Authors: Zhang Jiansong , Yuan Shuangling , Peng Qi , Ding Zhen , Hao Wenqi , Peng Guiqing , Xiao Shaobo , Fang Liurong
Published: April 2022

In recent years, an emerging porcine epidemic diarrhea virus (PEDV) variant has gained attention because of serious outbreaks of piglet diarrhea in China and the United States. Coronavirus nonstructural protein 7 (nsp7) has been proposed to act with nsp8 as part of an RNA primase to generate RNA primers for viral RNA synthesis.
Distinct Survival, Growth Lag, and rRNA Degradation Kinetics during Long-Term Starvation for Carbon or Phosphate
Authors: Himeoka Yusuke , Gummesson Bertil , Sørensen Michael A. , Svenningsen Sine Lo , Mitarai Namiko
Published: April 2022

The exponential growth of bacterial populations is punctuated by long or short periods of starvation lasting from the point of nutrient exhaustion until nutrients are replenished. To understand the consequences of long-term starvation for
Escherichia coli
cells, we performed month-long carbon and phosphorus starvation experiments and measured three key phenotypes of the cultures, namely, the survival of the cells, the time needed for them to resume growth after nutrient replenishment, and the levels of intact rRNA preserved in the cultures.
Genomic and Chemical Decryption of the Bacteroidetes Phylum for Its Potential to Biosynthesize Natural Products
Authors: Brinkmann Stephan , Kurz Michael , Patras Maria A. , Hartwig Christoph , Marner Michael , Leis Benedikt , Billion André , Kleiner Yolanda , Bauer Armin , Toti Luigi , Pöverlein Christoph , Hammann Peter E. , Vilcinskas Andreas , Glaeser Jens , Spohn Marius , Schäberle Till F.
Published: April 2022

The development of pipelines for anti-infectives to be applied in plant, animal, and human health management are dried up. However, the resistance development against compounds in use calls for new lead structures.
P32 Children’s hospital discharge collaborative: getting home in time for tea
Authors: Bell Catherine , Ashton Chloe , Brookes Andy , Jones Elliss , Forsaith Julia
Published: April 2022

Aim

The Children’s Hospital Discharge Collaborative (CHDC) team are a multi-disciplinary group of staff members passionate about improving the quality and efficiency of our discharges. The aim of this project is to increase the number of patients being discharged within working hours in order to facilitate a safe return to routine for families, improve patient flow within the hospital and ultimately improve patient experience.

Method

As a collaborative we have trialled interventions in ward areas, learnt what works and what needs improvement, all of which has enabled us to roll out evidence based changes throughout the Children’s Hospital. We have held monthly meetings and received good engagement from ward areas and a broad range of specialties which has meant that we have collaborated and shared ideas. The CHDC team have utilised existing morning huddles to identify potential discharges as early in the day as possible, or even the day before, as well as communicating this by the use of a discharge board visible to all staff members meaning that this information is readily available. We also challenged existing norms, and empowered leadership from within ward areas to drive projects. We have encouraged the early preparation - sometimes overnight - of quality discharges using a new acronym for electronic discharge advice notes (eDANs - Easy to read, Drugs, Advice, Next Steps). We have facilitated nurse-led and criteria led discharges as well as increased our safe use of over-labelled discharge packs. Another quality improvement project piloted the process of finalising the discharge medicines before the clinical information was completed enabling earlier dispensing.

Results

In the period from October 2020 to July 2021 the median percentage of weekly discharges before 1500hours has risen from 36% to 49%. In patient terms, this means approximately 18-20 more patients per week being discharged home before 1500hours.

Conclusion and Future Aspirations

The CHDC team have increased discharges before 1500hours across the Children’s Hospital by 13% over the last 9 months by working collaboratively and enthusiastically to rethink the existing processes used. This also equates to 1 or 2 wards full of patient space that is free for the next family that needs it. We hope to continue this good work and improve on this further by collecting some qualitative data from families to explore their thoughts about the discharge process.

The Trust is now investigating a re-design of the eDAN process to enable a change in discharge process across specialties, meaning that the whole Trust could benefit from this project’s initial work. The CHDC team also plan to continue to collaborate and celebrate our achievements, both locally and nationally by completing positive feedback forms, issuing certificates and ‘Discharge Champion’ badges and sharing our learning by presenting our work.
A summative content analysis of how programmes to improve the right to sexual and reproductive health address power
Authors: Schaaf Marta , Boydell Victoria , Topp Stephanie M , Iyer Aditi , Sen Gita , Askew Ian
Published: April 2022

Introduction

Power shapes all aspects of global health. The concept of power is not only useful in understanding the current situation, but it is also regularly mobilised in programmatic efforts that seek to change power relations. This paper uses summative content analysis to describe how sexual and reproductive health (SRH) programmes in low-income and middle-income countries explicitly and implicitly aim to alter relations of power.

Methods

Content analysis is a qualitative approach to analysing textual data; in our analysis, peer-reviewed articles that describe programmes aiming to alter power relations to improve SRH constituted the data. We searched three databases, ultimately including 108 articles. We extracted the articles into a spreadsheet that included basic details about the paper and the programme, including what level of the social ecological model programme activities addressed.

Results

The programmes reviewed reflect a diversity of priorities and approaches to addressing power, though most papers were largely based in a biomedical framework. Most programmes intervened at multiple levels simultaneously; some of these were ‘structural’ programmes that explicitly aimed to shift power relations, others addressed multiple levels using a more typical programme theory that sought to change individual behaviours and proximate drivers. This prevailing focus on proximate behaviours is somewhat mismatched with the broader literature on the power-related drivers of SRH health inequities, which explores the role of embedded norms and structures.

Conclusion

This paper adds value by summarising what the academic public health community has chosen to test and research in terms of power relations and SRH, and by raising questions about how this corresponds to the significant task of effecting change in power relations to improve the right to SRH.
Teams and continuity of end-of-life care in hospitals: managing differences of opinion
Authors: Devery Kim , Winsall Megan , Rawlings Deb
Published: April 2022

Background

Recognised as an essential element in end-of-life care by the Australian Commission on Safety and Quality in Health Care, effective teamwork can enhance the quality and safety of end-of-life care for patients in hospitals. End-of-Life Essentials (EOLE) is a Commonwealth funded project that delivers peer-reviewed, evidence-based, online education and practice change resources for doctors, nurses and allied health professionals working in hospitals. ‘Teams and Continuity for the Patient’ features in the suite of EOLE modules and includes education around effective teamwork in end-of-life care. The aim of this study was to explore the views of module learners on managing differences of opinion among staff regarding patient care management.

Methods

Participants were learners (health professionals) who registered to the EOLE website and engaged with the Teams module. Learner responses to a question posed at the end of the module ‘How do you manage differences of opinion among staff regarding patient care management?’ were extracted for a 12-month period. Qualitative data were analysed thematically in NVivo V.12, with pragmatism as an overarching theoretical framework. Data were coded using an inductive, open approach, and axial coding was used to organise the codes into themes and subthemes.

Findings

A total of 293 learner statements were analysed, with subthemes organised into three overarching themes:prioritising the patient, team collaborationandcommunication skills and emotional awareness.

Conclusion

In complex, fast-paced, hospital environments, the potential for conflict among teams is high. Quality care relies on team members who work in unison, who can also recognise conflict emerging and respond in respectful and appropriate ways. In this study, the management actions reported by health professionals as proving helpful when differences of opinion among team members arise, are valuable to organisations who are considering how to prepare for quality and safety accreditation.
Bempegaldesleukin plus nivolumab in first-line renal cell carcinoma: results from the PIVOT-02 study
Authors: Tannir Nizar M , Cho Daniel C , Diab Adi , Sznol Mario , Bilen Mehmet A , Balar Arjun V , Grignani Giovanni , Puente Erika , Tang Lily , Chien David , Hoch Ute , Choudhury Arkopal , Yu Danni , Currie Sue L , Tagliaferri Mary A , Zalevsky Jonathan , Siefker-Radtke Arlene O , Hurwitz Michael E
Published: April 2022

Background

Immune checkpoint inhibitor-based combinations have expanded the treatment options for patients with renal cell carcinoma (RCC); however, tolerability remains challenging. The aim of this study was to evaluate the safety and efficacy of the immunostimulatory interleukin-2 cytokine prodrug bempegaldesleukin (BEMPEG) plus nivolumab (NIVO) as first-line therapy in patients with advanced clear-cell RCC.

Methods

This was an open-label multicohort, multicenter, single-arm phase 1/2 study; here, we report results from the phase 1/2 first-line RCC cohort (N=49). Patients received BEMPEG 0.006 mg/kg plus NIVO 360 mg intravenously every 3 weeks. The primary objectives were safety and objective response rate (ORR; patients with measurable disease at baseline and at least one postbaseline tumor response assessment). Secondary objectives included overall survival (OS) and progression-free survival (PFS). Exploratory biomarker analyses: association between baseline biomarkers and ORR.

Results

At a median follow-up of 32.7 months, the ORR was 34.7% (17/49 patients); 3/49 patients (6.1%) had a complete response. Of the 17 patients with response, 14 remained in response for >6 months, and 6 remained in response for >24 months. Median PFS was 7.7 months (95% CI 3.8 to 13.9), and median OS was not reached (95% CI 37.3 to not reached). Ninety-eight per cent (48/49) of patients experienced ≥1 treatment-related adverse event (TRAE) and 38.8% (19/49) had grade 3/4 TRAEs, most commonly syncope (8.2%; 4/49) and increased lipase (6.1%; 3/49). No association between exploratory biomarkers and ORR was observed. Limitations include the small sample size and single-arm design.

Conclusions

BEMPEG plus NIVO showed preliminary antitumor activity as first-line therapy in patients with advanced clear-cell RCC and was well tolerated. These findings warrant further investigation.
Degeneration of topological string partition functions and mirror curves of the Calabi–Yau threefolds $$X_{N,M}$$
Authors: Ahmed Ambreen , Muteeb M. Nouman
Published: April 2022

In this article we study certain degenerations of the mirror curves associated with the Calabi–Yau threefolds $$X_{N,M}$$

X

N
,
M

, and the effect of these degenerations on the refined topological string partition function of $$X_{N,M}$$

X

N
,
M

. We show that when the mirror curve degenerates and become the union of the lower genus curves the corresponding partition function factorizes into pieces corresponding to the components of the degenerate mirror curve. Moreover we show that using degeneration of a generalised mirror curve it is possible to obtain the partition function corresponding to $$X_{N,M-1}$$

X

N
,
M
-
1

from $$X_{N,M}$$

X

N
,
M

.
Weak mean random attractors for non-local random and stochastic reaction–diffusion equations
Authors: Caballero Rubén , Marín-Rubio Pedro , Valero José
Published: April 2022

In this paper, we prove the existence of weak pullback mean random attractors for a non-local stochastic reaction–diffusion equation with a nonlinear multiplicative noise. The existence and uniqueness of solutions and weak pullback mean random attractors are also established for a deterministic non-local reaction–diffusion equations with random initial data.
An optimal control problem for a linear SPDE driven by a multiplicative multifractional Brownian motion
Authors: Grecksch Wilfried , Lisei Hannelore
Published: April 2022

In this paper, we study the existence of the solution of a linear SPDE driven by a multiplicative multifractional Brownian motion. Moreover, we study an optimal control problem with a linear quadratic objective functional involving the solution of the studied SPDE. We prove the existence and uniqueness of the optimal control.
A Five-Parameter Class of Derivative-Free Spectral Conjugate Gradient Methods for Systems of Large-Scale Nonlinear Monotone Equations
Authors: Bojari S. , Eslahchi M. R.
Published: April 2022

In this paper, we consider a system of large-scale nonlinear monotone equations and propose a class of derivative-free spectral conjugate gradient methods to solve it efficiently. We demonstrate the appropriate analytical features of this class and prove the global convergence theorems under a backtracking line search technique. In order to illustrate the numerical effectiveness of our class, we organize a competition in which 405 test problems will be solved by some members of the new class and four other similar derivative-free conjugate gradient methods. All the analytical and numerical results indicate that the presented class is promising.
Reactive molecular dynamic simulations of hydrogenation process of amorphous silicon nitride
Authors: Pamungkas Mauludi Ariesto , Widyaningrum Anisa , Istiroyah
Published: April 2022

Hydrogenated amorphous silicon nitride is useful as an anti-reflection coating on solar cells. The addition of hydrogen atoms to amorphous silicon nitride can reduce the dangling bonds that exist on the surface. The objective of this paper is to clarify on the behavior of hydrogen atoms absorbed in silicon nitride during the hydrogenation process at various temperatures. We investigate, in particular, the silicon and hydrogen bonds that are formed by the transfer of electrons from hydrogen to silicon to form [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text] ions. The conversion of [Formula: see text] ions into [Formula: see text] ions and then also into [Formula: see text] and [Formula: see text] occurs during enhancement of the hydrogen atoms absorbed. Hydrogenated amorphous silicon nitride was stabilized through the passivation of dangling bonds of silicon atoms and nitrogen atoms by the absorbed hydrogen atoms. The passivation was indicated by enhancement of over-coordinated silicon and nitrogen atoms as well as the reduction of under-coordinated silicon and nitrogen atoms. It was found that the thermal energy from high hydrogenation temperature was primarily used by hydrogen atoms to diffuse more and to penetrate deeper into silicon nitride rather than being used for the ionization of silicon atoms. Finally, we stress that these reactive molecular dynamic simulations have led to substantial progress in understanding how hydrogen atoms interact with amorphous silicon nitride during hydrogenation.
A Cyber-physical Approach for Emergency Braking in Close-Distance Driving Arrangements
Authors: Murthy Dharshan Krishna , Masrur Alejandro
Published: April 2022

In addition to fuel/energy savings, close-distance driving or platooning allows compacting vehicle flows and, hence, increasing throughput on congested roads. The shorter the inter-vehicle separation is in such settings, the more the benefits. However, it becomes considerably harder to guarantee safety, in particular, when braking in an emergency. In this article, we are concerned with this problem and propose a cyber-physical approach that considerably reduces the stopping distance of a platoon with inter-vehicle separations shorter than one vehicle length (i.e., 5 m) without sacrificing safety and independent of the road profile, i.e., whether on a flat road or in a downhill. The basic idea is to implement a cooperative behavior where a vehicle sends a distress message if it fails to achieve an assigned deceleration when braking in a platoon. This way, other vehicles in the arrangement can adapt their decelerations to avoid collisions. We illustrate and evaluate our approach based on detailed simulations involving high-fidelity vehicle models.
Review of Tales of Impossibility
Authors: Gasarch William
Published: April 2022

This book is about the 4 Greek problems of Antiquity. I will state them in a way that is absolutely whiggish.
Review of A Map that Reflects the Territory
Authors: Gasarch William
Published: April 2022

LessWrong is a forum founded by Artificial Intelligence Theorist Eliezer Yudkowsky and Economist Robin Hanson in 2009. The stated philosophy is: We are a community dedicated to improving our reasoning and decision-making. We seek to hold true beliefs and to be effective at accomplishing our goals. More generally, we work to develop and practice the art of human rationality.
Technical Report Column
Authors: Kelley Dean
Published: April 2022

Welcome to the Technical Reports Column. If your institution publishes technical reports that you'd like to have included here, please contact me at the email address above.
Evolving open complexity
Authors: Langdon W. B.
Published: April 2022

Information-theoretic analysis of large, evolved programs produced by running genetic programming for up to a million generations has shown even functions as smooth and well behaved as floating-point addition and multiplication lose entropy and consequently are robust and fail to propagate disruption to their outputs. This means that, while dependent upon fitness tests, many genetic changes deep within trees are silent. For evolution to proceed at a reasonable rate it must be possible to measure the impact of most code changes, yet in large trees, most crossover sites are distant from the root node. We suggest that to evolve very large, very complex programs, it will be necessary to adopt an open architecture where most mutation sites are within 10--100 levels of the organism's environment.
Static and Motion Facial Analysis for Craniofacial Assessment and Diagnosing Diseases
Authors: Matthews Harold , de Jong Guido , Maal Thomas , Claes Peter
Published: April 2022

Deviation from a normal facial shape and symmetry can arise from numerous sources, including physical injury and congenital birth defects. Such abnormalities can have important aesthetic and functional consequences. Furthermore, in clinical genetics distinctive facial appearances are often associated with clinical or genetic diagnoses; the recognition of a characteristic facial appearance can substantially narrow the search space of potential diagnoses for the clinician. Unusual patterns of facial movement and expression can indicate disturbances to normal mechanical functioning or emotional affect. Computational analyses of static and moving 2D and 3D images can serve clinicians and researchers by detecting and describing facial structural, mechanical, and affective abnormalities objectively. In this review we survey traditional and emerging methods of facial analysis, including statistical shape modeling, syndrome classification, modeling clinical face phenotype spaces, and analysis of facial motion and affect.
Predicting Archaic Hominin Phenotypes from Genomic Data
Authors: Brand Colin M. , Colbran Laura L. , Capra John A.
Published: April 2022

Ancient DNA provides a powerful window into the biology of extant and extinct species, including humans’ closest relatives: Denisovans and Neanderthals. Here, we review what is known about archaic hominin phenotypes from genomic data and how those inferences have been made. We contend that understanding the influence of variants on lower-level molecular phenotypes—such as gene expression and protein function—is a promising approach to using ancient DNA to learn about archaic hominin traits. Molecular phenotypes have simpler genetic architectures than organism-level complex phenotypes, and this approach enables moving beyond association studies by proposing hypotheses about the effects of archaic variants that are testable in model systems. The major challenge to understanding archaic hominin phenotypes is broadening our ability to accurately map genotypes to phenotypes, but ongoing advances ensure that there will be much more to learn about archaic hominin phenotypes from their genomes.
The Knowledge-Based Economy and the Global South
Authors: Chorev Nitsan , Ball Amanda C.
Published: April 2022

Research on knowledge-based economies and innovation tends to focus on the highest-ranked knowledge-advanced countries in the Global North and on high-growth countries in the Global South. In this article, we review the research on knowledge-based economies in the Global South and identify two important analytical shortcomings: the tendency to conflate upgrading with innovation and the tendency to focus on domestic factors. Moving beyond the familiar case studies, we explore the literature on pockets of knowledge-based industries in economies that are not dominantly knowledge-based. We then shift the focus from the private sector to explore the literature on state-led knowledge-based innovation, particularly welfare provisions and surveillance. We conclude by challenging the notion that innovation is simply the next step in industrial development and call for a more historically and geographically specific sociological approach to understanding innovation and knowledge-based industries, particularly in the Global South.
Centering Age Inequality: Developing a Sociology-of-Age Framework
Authors: Barrett Anne E.
Published: April 2022

The construct of age occupies a curious position in mainstream sociology: It is omnipresent but theoretically underdeveloped. The most prevalent approaches—age as control variable and age as life course—elide the aspect of age most relevant to the discipline, namely its operation as a system of inequality. Building on the foundation laid by scholars of life course sociology, age studies, and gerontology, I propose a new framework for thinking about age. The framework integrates insights from these fields and identifies inequality as a key axis on which several dimensions of age turn, thus placing age squarely in the domain of sociological research centering on inequalities. The article concludes with a discussion of how this framework can enhance the empirical and theoretical contributions of age-focused research. In particular, research that delves into how institutions, performances, and identities reproduce age inequality flows from this framework and constitutes a valuable contribution in its own right. Moreover, such an orientation positions the sociology of age as integral to the discipline, given its commitment to understanding how inequalities infuse social life.
In Situ Crosslinkable Collagen-Based Hydrogels for 3D Printing of Dermis-Mimetic Constructs
Authors: Kang Moon Sung , Kwon Mina , Lee So Yun , Lee Seok Hyun , Jo Hyo Jung , Kim Bongju , Kim Ki Su , Han Dong-Wook
Published: April 2022

Recently, several three-dimensional (3D) bioprinting techniques have emerged for the synthesis of 3D tissue analogs. Accordingly, many researchers have focused on the development of novel bioinks that can mimic the natural extracellular matrix with cytocompatibility and biofunctionality. Hyaluronic acid and collagen are the most abundant proteins in the extracellular matrix of the skin and are known to support several cellular behaviors. Herein, we developed tyramine-conjugated hyaluronic acid and collagen (HA-Tyr/Col-Tyr) hydrogel bioinks, which are photocrosslinkable in the presence of riboflavin and ammonium peroxydisulfate, to fabricate dermis-mimetic constructs. The physicochemical properties and 3D printability of the HA-Tyr/Col-Tyr hydrogel were examined. 3D printing of the lattice structure with the HA-Tyr/Col-Tyr hydrogel enabled a sophisticated micron-sized fine structure without any clogging or coagulation. Approximately 80% of normal human dermal fibroblasts (NHDFs) in the printed constructs were alive after 24 h of culture. Moreover, the 3D printed constructs supported 4.57-fold cell proliferation and 4.23-fold f-actin expansion over four days in culture, indicating that HA-Tyr/Col-Tyr hydrogels provide cytocompatible microenvironments. The findings of this study suggest that HA-Tyr/Col-Tyr hydrogels are promising candidates as bioinks for the 3D printing of dermis-mimetic constructs.
Granzyme B in epithelial barrier dysfunction and related skin diseases
Authors: Jung Karen , Pawluk Megan A. , Lane Michael , Nabai Layla , Granville David J.
Published: April 2022

The predominant function of the skin is to serve as a barrier—to protect against external insults and to prevent water loss. Junctional and structural proteins in the stratum corneum, the outermost layer of the epidermis, are critical to the integrity of the epidermal barrier as it balances ongoing outward migration, differentiation, and desquamation of keratinocytes in the epidermis. As such, epidermal barrier function is highly susceptible to upsurges of proteolytic activity in the stratum corneum and epidermis. Granzyme B is a serine protease scarce in healthy tissues but present at high levels in tissues encumbered by chronic inflammation. Discovered in the 1980s, granzyme B is currently recognized for its intracellular roles in immune cell-mediated apoptosis as well as extracellular roles in inflammation, chronic injuries, tissue remodeling, as well as processing of cytokines, matrix proteins, and autoantigens. Increasing evidence has emerged in recent years supporting a role for granzyme B in promoting barrier dysfunction in the epidermis by direct cleavage of barrier proteins and eliciting immunoreactivity. Likewise, granzyme B contributes to impaired epithelial function of the airways, retina, gut, and vessels. In the present review, the role of granzyme B in cutaneous epithelial dysfunction is discussed in the context of specific conditions with an overview of underlying mechanisms as well as utility of current experimental and therapeutic inhibitors.
Even well-practiced movements benefit from repetition
Authors: Sutter Katrin , Oostwoud Wijdenes Leonie , van Beers Robert J. , Medendorp W. Pieter
Published: April 2022

Professional athletes practice movements that they have performed thousands of times in training just before it is their turn in a game. Why do they do this? Our results indicate that both initial and endpoint variability reduce with repetition in a short sequence of reaching movements. This means that even well-practiced movements benefit from practice.
Gut microbiota of wild fish as reporters of compromised aquatic environments sleuthed through machine learning
Authors: Turner John W. , Cheng Xi , Saferin Nilanjana , Yeo Ji-Youn , Yang Tao , Joe Bina
Published: April 2022

Human-generated negative impacts on aquatic environments are rising. Despite wild fish playing a key role in aquatic ecologies and comprising a major global food source, physiological consequences of these impacts on them are poorly understood. Here we address the issue through the lens of interrelationship between wild fish and their gut microbiota, hypothesizing that fish microbiota are reporters of the aquatic environs. Two geographically separate teleost wild-fish species were studied (Lake Erie, Ohio, and Caribbean Sea, US Virgin Islands). At each geolocation, fresh fecal samples were collected from fish in areas of presence or absence of known aquatic compromise. Gut microbiota was assessed via microbial 16S-rRNA gene sequencing and represents the first complete report for both fish species. Despite marked differences in geography, climate, water type, fish species, habitat, diet, and gut microbial compositions, the pattern of shifts in microbiota shared by both fish species was nearly identical due to aquatic compromise. Next, these data were subjected to machine learning (ML) to examine reliability of using the fish-gut microbiota as an ecomarker for anthropogenic aquatic impacts. Independent of geolocation, ML predicted aquatic compromise with remarkable accuracy (>90%). Overall, this study represents the first multispecies stress-related comparison of its kind and demonstrates the potential of artificial intelligence via ML as a tool for biomonitoring and detecting compromised aquatic conditions.