bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune modulation by nutritional intervention in malnourished children: Identifying the phenotypic distribution and functional responses of peripheral blood mononuclear cells
Authors: Noor Zannatun , Hasan Md. Mehedi , Gazi Md. Amran , Hossaini Farzana , Haque Nur Muhammad Shahedul , Palit Parag , Fahim Shah Mohammad , Das Subhasish , Mahfuz Mustafa , Marie Chelsea , Petri William A. , Haque Rashidul , Ahmed Tahmeed
Published: May 2023

Malnourished children are susceptible to an increased risk of mortality owing to impaired immune functions. However, the underlying mechanism of altered immune functions and its interaction with malnutrition is poorly understood. This study investigates the immune function and evaluates the effect of a particular nutritional intervention on the immune cells of undernourished children. Stunted (LAZ <−2) and at‐risk of being stunted (length‐for‐age Z‐scores, LAZ <−1 to −2) children aged between 12 and 18 months were enrolled and were provided with the daily nutritional intervention of one egg and 150 mL cow's milk for 90 days. Peripheral blood mononuclear cells (PBMCs) were isolated at enrolment and upon completion of the intervention. Phenotypic profiles for CD3+ cells, CD4+ cells, CD8+ cells, NKT cells, and B cells were similar in both cohorts, both before and after the intervention. However, activated B cells (CD25+) were increased after nutritional intervention in the at‐risk of being stunted cohort. Several pro‐inflammatory cytokines, IL‐6, IFN‐γ, and TNF‐α, were elevated in the stunted children following the nutritional intervention. The results of the study indicate that nutritional intervention may have a role on activated B cells (CD25+) s in children who are at‐risk of being stunted and may alter the capacity of PBMC to produce inflammatory cytokines in stunted children.
Co-Ingestion of Branched-Chain Amino Acids and Carbohydrate Stimulates Myofibrillar Protein Synthesis Following Resistance Exercise in Trained Young Men
Authors: Jackman Sarah R. , Wallis Gareth A. , Yu Jinglei , Philp Andrew , Baar Keith , Tipton Kevin D. , Witard Oliver C.
Published: May 2023

Branched-chain amino acids (BCAA) and carbohydrate (CHO) are commonly recommended postexercise supplements. However, no study has examined the interaction of CHO and BCAA ingestion on myofibrillar protein synthesis (MyoPS) rates following exercise. We aimed to determine the response of MyoPS to the co-ingestion of BCAA and CHO following an acute bout of resistance exercise. Ten resistance-trained young men completed two trials in counterbalanced order, ingesting isocaloric drinks containing either 30.6-g CHO plus 5.6-g BCAA (B + C) or 34.7-g CHO alone following a bout of unilateral, leg resistance exercise. MyoPS was measured postexercise with a primed, constant infusion of L-[ring13C6] phenylalanine and collection of muscle biopsies pre- and 4 hr postdrink ingestion. Blood samples were collected at time points before and after drink ingestion. Serum insulin concentrations increased to a similar extent in both trials (p > .05), peaking at 30 min postdrink ingestion. Plasma leucine (514 ± 34 nmol/L), isoleucine (282 ± 23 nmol/L), and valine (687 ± 33 nmol/L) concentrations peaked at 0.5 hr postdrink in B + C and remained elevated for 3 hr during exercise recovery. MyoPS was ∼15% greater (95% confidence interval [−0.002, 0.028], p = .039, Cohen’s d = 0.63) in B + C (0.128%/hr ± 0.011%/hr) than CHO alone (0.115%/hr ± 0.011%/hr) over the 4 hr postexercise period. Co-ingestion of BCAA and CHO augments the acute response of MyoPS to resistance exercise in trained young males.
The Dissemination and Implementation of Recess Guidelines, Policies, and Practices During the COVID-19 Pandemic
Authors: Olsen Edward B. , Tsuda Emi , Wyant James D. , Burrell Ranaysia , Mukherjee Jessica , McKay Ara , Herrera Joseph , Labrador David
Published: May 2023

Purpose: There are limited school physical activity policy dissemination and implementation studies. This is a concern given the adverse mental, physical, and socio-emotional effects the COVID-19 pandemic has had on children and adolescents. This study explored New Jersey school administrators’ experiences in disseminating recess guidelines, procedures, and policies as well as implementation strategies in their schools during the pandemic. Methods: A total of 29 elementary school administrators participated in semi-structured interviews. The data were analyzed inductively using a conventional approach to qualitative content analysis. Results: In analyzing the data, five themes were identified: (a) adjustments for recess, (b) communications about recess, (c) successes and challenges of recess, (d) health and well-being among children, and (e) recommendations for recess postpandemic. Discussion/Conclusion: When planning, organizing, and implementing a recess in a postpandemic era, school leaders may want to consider establishing cohorts, developing a handbook, creating a rotation schedule (i.e., blacktop, field, playground), developing a recess committee, utilizing the physical education teacher for staff development, assigning recess equipment and bags, offering a variety of activities, and teaching children how to play.
Molecular insights into the evolution of woody plant decay in the gut of termites
Authors: Li Hongjie , Kang Xue , Yang Mengyi , Kasseney Boris Dodji , Zhou Xuguo , Liang Shiyou , Zhang Xiaojie , Wen Jia-Long , Yu Baoting , Liu Ning , Zhao Yufen , Mo Jianchu , Currie Cameron R. , Ralph John , Yelle Daniel J.
Published: May 2023

Plant cell walls represent the most abundant pool of organic carbon in terrestrial ecosystems but are highly recalcitrant to utilization by microbes and herbivores owing to the physical and chemical barrier provided by lignin biopolymers. Termites are a paradigmatic example of an organism’s having evolved the ability to substantially degrade lignified woody plants, yet atomic-scale characterization of lignin depolymerization by termites remains elusive. We report that the phylogenetically derived termite
Nasutitermes
sp. efficiently degrades lignin via substantial depletion of major interunit linkages and methoxyls by combining isotope-labeled feeding experiments and solution-state and solid-state nuclear magnetic resonance spectroscopy. Exploring the evolutionary origin of lignin depolymerization in termites, we reveal that the early-diverging woodroach
Cryptocercus darwini
has limited capability in degrading lignocellulose, leaving most polysaccharides intact. Conversely, the phylogenetically basal lineages of “lower” termites are able to disrupt the lignin-polysaccharide inter- and intramolecular bonding while leaving lignin largely intact. These findings advance knowledge on the elusive but efficient delignification in natural systems with implications for next-generation ligninolytic agents.
Charting a high-resolution roadmap for regeneration of pancreatic β cells by in vivo transdifferentiation from adult acinar cells
Authors: Liu Gang , Li Yana , Li Mushan , Li Sheng , He Qing , Liu Shuxin , Su Qiang , Chen Xiangyi , Xu Minglu , Zhang Zhen-Ning , Shao Zhen , Li Weida
Published: May 2023

Adult mammals have limited capacity to regenerate functional cells. Promisingly, in vivo transdifferentiation heralds the possibility of regeneration by lineage reprogramming from other fully differentiated cells. However, the process of regeneration by in vivo transdifferentiation in mammals is poorly understood. Using pancreatic β cell regeneration as a paradigm, we performed a single-cell transcriptomic study of in vivo transdifferentiation from adult mouse acinar cells to induced β cells. Using unsupervised clustering analysis and lineage trajectory construction, we uncovered that the cell fate remodeling trajectory was linear at the initial stage and the reprogrammed cells either evolved to induced β cells or toward a “dead-end” state after day 4.Moreover, functional analyses identified both
p53
and
Dnmt3a
that acted as reprogramming barriers during the process of in vivo transdifferentiation. Collectively, we decipher a high-resolution roadmap of regeneration by in vivo transdifferentiation and provide a detailed molecular blueprint to facilitate mammalian regeneration.
A first-in-human germline-targeting HIV nanoparticle vaccine induced broad and publicly targeted helper T cell responses
Authors: Cohen Kristen W. , De Rosa Stephen C. , Fulp William J. , deCamp Allan C. , Fiore-Gartland Andrew , Mahoney Celia R. , Furth Sarah , Donahue Josh , Whaley Rachael E. , Ballweber-Fleming Lamar , Seese Aaron , Schwedhelm Katharine , Geraghty Daniel , Finak Greg , Menis Sergey , Leggat David J. , Rahaman Farhad , Lombardo Angela , Borate Bhavesh R. , Philiponis Vincent , Maenza Janine , Diemert David , Kolokythas Orpheus , Khati Nadia , Bethony Jeffrey , Hyrien Ollivier , Laufer Dagna S. , Koup Richard A. , McDermott Adrian B. , Schief William R. , McElrath M. Juliana
Published: May 2023

The engineered outer domain germline targeting version 8 (eOD-GT8) 60-mer nanoparticle was designed to prime VRC01-class HIV-specific B cells that would need to be matured, through additional heterologous immunizations, into B cells that are able to produce broadly neutralizing antibodies. CD4 T cell help will be critical for the development of such high-affinity neutralizing antibody responses. Thus, we assessed the induction and epitope specificities of the vaccine-specific T cells from the IAVI G001 phase 1 clinical trial that tested immunization with eOD-GT8 60-mer adjuvanted with AS01B. Robust polyfunctional CD4 T cells specific for eOD-GT8 and the lumazine synthase (LumSyn) component of eOD-GT8 60-mer were induced after two vaccinations with either the 20- or 100-microgram dose. Antigen-specific CD4 T helper responses to eOD-GT8 and LumSyn were observed in 84 and 93% of vaccine recipients, respectively. CD4 helper T cell epitope “hotspots” preferentially targeted across participants were identified within both the eOD-GT8 and LumSyn proteins. CD4 T cell responses specific to one of these three LumSyn epitope hotspots were observed in 85% of vaccine recipients. Last, we found that induction of vaccine-specific peripheral CD4 T cells correlated with expansion of eOD-GT8–specific memory B cells. Our findings demonstrate strong human CD4 T cell responses to an HIV vaccine candidate priming immunogen and identify immunodominant CD4 T cell epitopes that might improve human immune responses either to heterologous boost immunogens after this prime vaccination or to other human vaccine immunogens.
A multi-specific, multi-affinity antibody platform neutralizes sarbecoviruses and confers protection against SARS-CoV-2 in vivo
Authors: Burn Aschner Clare , Muthuraman Krithika , Kucharska Iga , Cui Hong , Prieto Katherine , Nair Manoj S. , Wang Maple , Huang Yaoxing , Christie-Holmes Natasha , Poon Betty , Lam Jessica , Sultana Azmiri , Kozak Robert , Mubareka Samira , Rubinstein John L. , Rujas Edurne , Treanor Bebhinn , Ho David D. , Jetha Arif , Julien Jean-Philippe
Published: May 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has been responsible for a global pandemic. Monoclonal antibodies (mAbs) have been used as antiviral therapeutics; however, these therapeutics have been limited in efficacy by viral sequence variability in emerging variants of concern (VOCs) and in deployment by the need for high doses. In this study, we leveraged the multi-specific, multi-affinity antibody (Multabody, MB) platform, derived from the human apoferritin protomer, to enable the multimerization of antibody fragments. MBs were shown to be highly potent, neutralizing SARS-CoV-2 at lower concentrations than their corresponding mAb counterparts. In mice infected with SARS-CoV-2, a tri-specific MB targeting three regions within the SARS-CoV-2 receptor binding domain was protective at a 30-fold lower dose than a cocktail of the corresponding mAbs. Furthermore, we showed in vitro that mono-specific MBs potently neutralize SARS-CoV-2 VOCs by leveraging augmented avidity, even when corresponding mAbs lose their ability to neutralize potently, and that tri-specific MBs expanded the neutralization breadth beyond SARS-CoV-2 to other sarbecoviruses. Our work demonstrates how avidity and multi-specificity combined can be leveraged to confer protection and resilience against viral diversity that exceeds that of traditional monoclonal antibody therapies.
Novel Non-Hot Spot Modification in Fks1 of Candida auris Confers Echinocandin Resistance
Authors: Kordalewska Milena , Cancino-Prado Geselle , Nobrega de Almeida Júnior João , Brasil Brandão Igor , Tigulini de Souza Peral Renata , Colombo Arnaldo L. , Perlin David S.
Published: May 2023

We determined the echinocandin susceptibility and
FKS1
genotypes of 13 clinical isolates of
Candida auris
that were recovered from 4 patients at a tertiary care center in Salvador, Brazil. Three isolates were categorized as echinocandin-resistant, and they harbored a novel
FKS1
mutation that led to an amino acid change W691L located downstream from hot spot 1.
Environmental Factors Influencing Occurrence of Vibrio parahaemolyticus and Vibrio vulnificus
Authors: Brumfield Kyle D. , Chen Arlene J. , Gangwar Mayank , Usmani Moiz , Hasan Nur A. , Jutla Antarpreet S. , Huq Anwar , Colwell Rita R.
Published: May 2023

The genus
Vibrio
includes pathogenic species that are naturally occurring in marine and estuarine environments globally. Routine monitoring for
Vibrio
species and environmental parameters influencing their incidence is critical to provide a warning system for the public when the risk of infection is high.
PBP2b Mutations Improve the Growth of Phage-Resistant
Lactococcus cremoris
Lacking Polysaccharide Pellicle
Authors: Guérin Hugo , Quénée Pascal , Palussière Simon , Courtin Pascal , André Gwenaëlle , Péchoux Christine , Costache Vlad , Mahony Jennifer , van Sinderen Douwe , Kulakauskas Saulius , Chapot-Chartier Marie-Pierre
Published: May 2023

Lactococcus lactis
and
Lactococcus cremoris
are widely used in the dairy industry as a starter culture. As such, they are consistently challenged by bacteriophage infections which may result in reduced or failed milk acidification with associated economic losses.
Direct-from-Blood Detection of Pathogens: a Review of Technology and Challenges
Authors: Samuel Linoj
Published: May 2023

Blood cultures have been the staple of clinical microbiology laboratories for well over half a century, but gaps remain in our ability to identify the causative agent in patients presenting with signs and symptoms of sepsis. Molecular technologies have revolutionized the clinical microbiology laboratory in many areas but have yet to present a viable alternative to blood cultures. There has been a recent surge of interest in utilizing novel approaches to address this challenge.
Highly sensitive detection of antimicrobial resistance genes in hospital wastewater using the multiplex hybrid capture target enrichment
Authors: Baba Hiroaki , Kuroda Makoto , Sekizuka Tsuyoshi , Kanamori Hajime
Published: May 2023

Wastewater can be useful in monitoring the spread of antimicrobial resistance (AMR) within a hospital. The abundance of antibiotic resistance genes (ARGs) in hospital effluent was assessed using metagenomic sequencing (mDNA-seq) and hybrid capture (xHYB). mDNA-seq analysis and subsequent xHYB targeted enrichment were conducted on two effluent samples per month from November 2018 to May 2021. Reads per kilobase per million (RPKM) values were calculated for all 1,272 ARGs in the constructed database. The monthly numbers of patients with presumed extended-spectrum β-lactamase (ESBL)-producing and metallo-β-lactamase (MBL)-producing bacteria, methicillin-resistant
Staphylococcus aureus
(MRSA), and vancomycin-resistant enterococci (VRE) were compared with the monthly RPKM values of
bla
CTX-M
,
bla
IMP
,
mecA
,
vanA
, and
vanB
by xHYB. The average RPKM value for all ARGs detected by xHYB was significantly higher than that of mDNA-seq (665, 225, and 328, respectively, and
P
< 0.05). The average number of patients with ESBL producers and RPKM values of
bla
CTX-M-1
genes in 2020 were significantly higher than that in 2019 (17 and 13 patients per month and 921 vs 232 per month, respectively, both
P
< 0.05). The average numbers of patients with MBL-producers, MRSA, and VRE were 1, 28, and 0 per month, respectively, while the average RPKM values of
bla
IMP
,
mecA
,
vanA
, and
vanB
were 6,163, 6, 0, and 126 per month, respectively. Monitoring ARGs in hospital effluent using xHYB was found to be more useful than conventional mDNA-seq in detecting ARGs including
bla
CTX-M
,
bla
IMP,
and
vanB
, which are important for infection control.

IMPORTANCE

Environmental ARGs play a crucial role in the emergence and spread of AMR that constitutes a significant global health threat. One major source of ARGs is effluent from healthcare facilities, where patients are frequently administered antimicrobials. Culture-independent methods, including metagenomics, can detect environmental ARGs carried by non-culturable bacteria and extracellular ARGs. mDNA-seq is one of the most comprehensive methods for environmental ARG surveillance; however, its sensitivity is insufficient for wastewater surveillance. This study demonstrates that xHYB appropriately monitors ARGs in hospital effluent for sensitive identification of nosocomial AMR dissemination. Correlations were observed between the numbers of inpatients with antibiotic-resistant bacteria and the ARG RPKM values in hospital effluent over time. ARG surveillance in hospital effluent using the highly sensitive and specific xHYB method could improve our understanding of the emergence and spread of AMR within a hospital.
Biocontrol of Fusarium Species Utilizing Indigenous Rooibos and Honeybush Extracts
Authors: Omoruyi Beauty E. , Volschenk Heinrich , Gelderblom Wentzel C. A. , Lilly Mariska
Published: May 2023

In maize subsistence farming areas in South Africa, daily consumption of maize contaminated by high level of mycotoxins contributes to long-term health effects such as immune deficiency and cancer. Biocontrol methods that are safe and cost-effective are critical to addressing this public health problem.
Root Niches of Blueberry Imprint Increasing Bacterial-Fungal Interkingdom Interactions along the Soil-Rhizosphere-Root Continuum
Authors: Che Jilu , Wu Yaqiong , Yang Hao , Wang Shaoyi , Wu Wenlong , Lyu Lianfei , Wang Xiaomin , Li Weilin
Published: May 2023

The blueberry root-associated microbiome plays an essential role in its adaptation to acidic soils and in limiting the uptake of soil nutrients by its poor root system. Studies on the interactions of the root-associated microbiome in the various root niches may deepen our understanding of the beneficial effects in this particular habitat.
A C. albicans TRAPP Complex-Associated Gene Contributes to Cell Wall Integrity, Hyphal and Biofilm Formation, and Tissue Invasion
Authors: Ma Dakota , Yu Miranda , Eszterhas Susan , Rollenhagen Christiane , Lee Samuel A.
Published: May 2023

The fungal pathogen
Candida albicans
causes serious opportunistic infections in immunocompromised patients and has become a major cause of hospital-acquired bloodstream infections, catheter-associated infections, and invasive disease. However, due to a limited understanding of
Candida
molecular pathogenesis, clinical approaches for the prevention, diagnosis, and treatment of invasive candidiasis need significant improvement.
Herpes simplex virus infection among neonates suspected of invasive bacterial infection: a population-based cohort study
Authors: Dungu Kia Hee Schultz , Lund Stine , Malchau Carlsen Emma Louise , Hartling Ulla Birgitte , Matthesen Astrid Thaarup , Franck Kristina Træholt , Thomsen Marianne Kragh , Justesen Ulrik Stenz , Nielsen Hans Linde , Nielsen Alex Christian Yde , Henriksen Tine Brink , Nygaard Ulrikka
Published: May 2023

Objective

To estimate the incidence of neonatal herpes simplex virus (HSV) infection and the number of neonates with suspected invasive bacterial infection (IBI) needed to treat (NNT) with acyclovir to ensure prompt treatment of invasive HSV infections.

Design

A nationwide population-based cohort study.

Setting

All neonatal and paediatric emergency departments in Denmark from 1 January 2010 to 31 December 2019.

Patients

Neonates aged 0–28 days with HSV infection.

Main outcome measures

The main outcome measures were incidence and NNT. The NNT was calculated based on neonates with invasive HSV infection whose onset symptoms resembled IBI and the estimated number of Danish neonates who received antibiotics for suspected IBI.

Results

Fifty-four neonates with HSV infection were identified, that is, an incidence of 9 per 100 000 live births. Twenty presented with symptoms resembling IBI, all within the first 14 days of life. Of 18 (78%) neonates, 14 had elevated C reactive protein, 14 of 19 (74%) had elevated alanine aminotransferase and 11 of 17 (65%) had thrombocytopaenia. The estimated NNTs with empiric acyclovir at postnatal ages 0–3, 4–7 and 8–14 days were 1139 (95% CI 523 to 3103), 168 (95% CI 101 to 726) and 117 (95% CI 48 to 198), respectively.

Conclusions

The incidence of neonatal HSV infection was higher than in previous decades; however, the estimated NNT with empiric acyclovir was high. Therefore, we propose not to treat all neonates suspected of IBI with empiric acyclovir, as current European guidelines suggest. However, HSV should be considered in neonates with signs of infection, especially after the third postnatal day and in neonates with high alanine aminotransferases and thrombocytopaenia.
Pre-emptive coinfiltration of dexamethasone palmitate emulsion with ropivacaine for postoperative pain in patients undergoing major spine surgery: a study protocol for a prospective, randomised controlled, multicentre trial
Authors: Yu Bin , Wang Baoguo , Shrestha Niti , Luo Fang
Published: May 2023

Introduction

Patients undergoing major spine surgery usually experience moderate-to-severe postoperative pain. It has been shown that dexamethasone as an adjunct to local anaesthesia (LA) infiltration presented a superior analgesic benefit compared with LA alone in various types of surgeries. However, a recent meta-analysis reported that the overall benefits of dexamethasone infiltration were marginal. Dexamethasone palmitate (DXP) emulsion is a targeted liposteroid. Compared with dexamethasone, DXP has a stronger anti-inflammatory effect, longer duration of action and fewer adverse effects. We hypothesised that the additive analgesic effects of DXP on local incisional infiltration in major spine surgery may have better postoperative analgesic effect, compared with local anaesthetic alone. However, no study has evaluated this so far. The purpose of this trial is to determine whether pre-emptive coinfiltration of DXP emulsion and ropivacaine at surgical site incision will further reduce postoperative opioid requirements and pain scores after spine surgery than that with ropivacaine alone.

Methods and analysis

This is a prospective, randomised, open-label, blinded endpoint, multicentre study. 124 patients scheduled for elective laminoplasty or laminectomy with no more than three levels will be randomly allocated in a 1:1 ratio into two groups: the intervention group will receive local incision site infiltration with ropivacaine plus DXP; the control group will receive infiltration with ropivacaine alone. All participants will complete a 3 months follow-up. The primary outcome will be the cumulative sufentanil consumption within 24 hours after surgery. The secondary outcomes will include further analgesia outcome assessments, steroid-related side effects and other complications, within the 3 months follow-up period.

Ethics and dissemination

This study protocol has been approved by the Institutional Review Board of Beijing Tiantan Hospital (KY-2019-112-02-3). All participants will provide a written informed consent. The results will be submitted for publication in a peer-reviewed journals.

Trial registration number

NCT05693467.
Enhancing social value considerations in prioritising publicly funded biomedical research: the vital role of peer review
Authors: Saylor Katherine W , Joffe Steven
Published: May 2023

The main goal of publicly funded biomedical research is to generate social value through the creation and application of knowledge that can improve the well-being of current and future people. Prioritising research with the greatest potential social value is crucial for good stewardship of limited public resources and ensuring ethical involvement of research participants. At the National Institutes of Health (NIH), peer reviewers hold the expertise and responsibility for social value assessment and resulting prioritisation at the project level. However, previous research has shown that peer reviewers place more emphasis on a study’s methods (‘Approach’) than on its potential social value (best approximated by the criterion of ‘Significance’). Lower weighting of Significance may be due to reviewers’ views on the relative importance of social value, their belief that social value is evaluated at other stages of the research priority-setting process or the lack of guidance on how to approach the challenging task of assessing expected social value. The NIH is currently revising its review criteria and how these criteria contribute to overall scores. To elevate the role of social value in priority setting, the agency should support empirical research on how peer reviewers approach the assessment of social value, provide more specific guidance for reviewing social value and experiment with alternative reviewer assignment strategies. These recommendations would help ensure that funding priorities align with the NIH’s mission and the obligation of taxpayer-funded research to contribute to the public good.
Oral ketamine for neuropathic cancer pain
Authors: Calsina-Berna Agnès , Alvaro Pardo Margarita , Cucurull Salamero Marc , Bleda-Perez Montserrat , Julià-Torras Joaquim
Published: May 2023

Optimal pain management in patients with advanced cancer often requires multiple pharmacological interventions and multimodal approach. Ketamine is an anaesthetic agent with increasing evidence supporting its use for pain. Due to its N-methyl-D-aspartate antagonism and its activity at opioid receptors, it is an adjuvant to traditional analgesics. Ketamine has a safety profile with limited experience of oral prolonged use in patients with cancer. We report a case of a 40-year-old man with refractory neuropathic cancer-related pain. Opioid rotation to methadone was previously performed, coanalgesics were added, the patient was reluctant to invasive anaesthetic techniques and his pain was poorly controlled. Ketamine was added to attenuate pain keeping functionality. This is a report of a patient with refractory cancer pain treated with methadone and ketamine orally during months, without reported side effects. Ketamine’s use to treat pain is increasing along with its evidence of efficacy for long-term oral use.
Nunaaqqit Savaqatigivlugich—working with communities: evolving collaborations around an Alaska Arctic observatory and knowledge hub
Authors: Hauser Donna D.W. , Glenn Roberta Tuurraq , Lindley Elizabeth D. , Pikok Kimberly Kivvaq , Heeringa Krista , Jones Joshua , Adams Billy , Leavitt Joe Mello , Omnik Guy Norman , Schaeffer Robert , SimsKayotuk Carla , Sparrow Elena Bautista , Ravelo Alexandra M. , Lee Olivia , Eicken Hajo
Published: May 2023

Indigenous Peoples across the Arctic have adapted to environmental change since time immemorial, yet recent climate change has imposed unprecedented and abrupt changes that affect the land and sea upon which communities rely. Co-created community-based observing programs offer an opportunity to harness the holistic breadth of knowledge in communities with the goal of tracking Arctic change while simultaneously supporting community priorities and local-scale needs. The Alaska Arctic Observatory and Knowledge Hub (AAOKH) is a network of Iñupiaq observers from northern Alaska coastal communities working in partnership with academic researchers. Here, we describe five core functions that have emerged through AAOKH, which include tracking long-term environmental changes; communicating Indigenous-led observations of the environment and their meaning; place-based and culturally relevant education; enabling scientific and Indigenous Knowledge exchange; and supporting community-led responses to environmental change. We outline and discuss specific actions and opportunities that have been used to increase knowledge exchange of AAOKH observations, make space for the next generation of Indigenous scholars, and create locally relevant data products and syntheses that can inform resource management and community planning. We also discuss our ongoing efforts to increasingly shift toward a knowledge coproduction framework as we plan to sustain AAOKH into the future.
Visualized direct shear test of the interface between gravelly sand and concrete pipe
Authors: Li Tianliang , Zhao Wen , Liu Run , Han Jianyong , Jia Pengjiao , Cheng Cheng
Published: May 2023

The shear stress–shear displacement relationship and shear strength parameters of the interface between the pipe and the surrounding soil are important for designing the jacking force. One most commonly used method to measure the shear strength of the pipe–soil interface is the direct shear test. This paper presents the results of a series of direct shear tests conducted in the laboratory on the pipe–soil interfaces for different moisture contents. Simultaneously, digital image correlation is used to supplement the research of the horizontal displacement field of the interface. The results show that the increase of normal stress will makes the interface more prone to strain hardening during the shearing process, and the influence of the change of specimen moisture content on the interface strain characteristics gradually weakens. The shearing process of the specimen mainly involved shearing contraction, and slight shear dilation occurs only when the moisture content is small. We proposed a unified model for describing the shear volumetric change caused by the combined action of moisture content and normal stress. The shear displacement field presents a layered distribution, which is related to the shear displacement corresponding to the shear stress.
Petrogenesis and tectonic significance of the Early Cretaceous Xizhelimu diorite in Keyouzhongqi, Inner Mongolia, China
Authors: Tian Li , Sun Deyou , Gou Jun , He Zhonghua , Zhang Duo
Published: May 2023

To determine the emplacement age, petrogenesis, and geodynamic setting of the Xizhelimu diorite in Keyouzhongqi, Inner Mongolia of northeastern China, a detailed study of the petrography, geochronology, and whole-rock geochemistry has been conducted. Geological and petrographic studies show that the Xizhelimu diorite is zoned: the central lithofacies zone is composed of medium-fine-grained monzodiorite and quartz diorite, and the marginal lithofacies zone is fine-grained diorite. The zircon U–Pb dating results show that the ages of the central and marginal facies are 133.5 ± 1.9 and 133.4 ± 1.4 Ma, respectively. The whole-rock rare earth and trace element characteristics of the Xizhelimu diorite show an O-type adakite affinity. Combining the analysis of zircon Hf isotope composition ( εHf(t) values of +7.7 to +10.0), the geochemical features of whole rock, and the results of partial melting modeling, we suggest that the parental magma of the Xizhelimu diorite was derived from the partial melting of altered oceanic crust mixing with subducting sediments at shallow depths. In the early stage of early Cretaceous, the Xizhelimu diorite originated in an extensional setting, mainly related to the closure of the western part of the Mongol–Okhotsk Ocean. The upwelling asthenospheric flow in this extensional setting induced partial melting of the paleo-oceanic crust to form the parental magma of the Xizhelimu diorite.
Therapeutic effect of ouabagenin, a novel liver X receptor agonist, on atherosclerosis in nonalcoholic steatohepatitis in SHRSP5/Dmcr rat model
Authors: Yamamoto Shusei , Sato Ikumi , Fujii Moe , Kakimoto Mai , Honma Koki , Kirihara Sora , Nakayama Hinako , Fukuoka Taketo , Tamura Satoru , Ueda Minoru , Hirohata Satoshi , Watanabe Shogo
Published: May 2023

The liver X receptor (LXR) can enhance cholesterol transporters, which could remove excess cholesterol from foam cells in atheromas. LXR has two subtypes: LXRα, which aggravates hepatic lipid accumulation, and LXRβ, which does not. In 2018, ouabagenin (OBG) was reported as a potential LXRβ-specific agonist. We aimed to examine whether OBG specifically affects LXRβ in nonalcoholic steatohepatitis (NASH); it did not aggravate hepatic steatosis and can suppress the development of atherosclerosis. SHRSP5/Dmcr rats fed a high-fat and high-cholesterol diet were divided into four groups as follows: (I) L-NAME group, (II) L-NAME/OBG group, (III) OBG (−) group, and (IV) OBG (+) group. All groups’ rats were intraperitoneally administered L-NAME. The L-NAME/OBG group’s rats were intraperitoneally administered OBG and L-NAME simultaneously. After L-NAME administration, the OBG (+) group’s rats were administered OBG, while the OBG (−) group’s rats were not. Although all rats developed NASH, OBG did not exacerbate steatosis (L-NAME/OBG and OBG (+) groups). In addition, endothelial cells were protected in the L-NAME/OBG group and foam cells in the atheroma were reduced in the OBG (+) group. OBG is an LXRβ-specific agonist and has a potential therapeutic effect on atherosclerosis without developing lipid accumulation in the liver.
A vacuum solution of modified Einstein equations based on fractional calculus
Authors: Di Teodoro A. , Contreras E.
Published: May 2023

In this work, we construct a modified version of the Einstein field equations for a vacuum and spherically symmetric spacetime in terms of the Riemann–Liouville fractional derivative. The main difference between our approach and other works is that we ensure that both the classical differential equations and the classical solutions are exactly recovered in the limit when the fractional parameter is turned off. We assume that the fractional equations are valid inside and near the horizon radius and match the classical solution at the horizon. Our approach resembles the Herrera–Witten strategy (Adv High Energy Phys 2018:3839103, 2018, https://doi.org/10.1155/2018/3839103, arXiv:1806.07143 [gr-qc]), where the authors constructed an alternative black hole solution by assuming that inside the horizon the spacetime is hyperbolically symmetric and matches the classical spherically symmetric exterior solution at one point at the horizon. We obtain that, depending on the value of the fractional parameter, the solutions can be interpreted as a regular black hole or a gravastar. As a final step, we compute the fractional curvature scalars and show that the solution is regular everywhere inside the horizon.
Integrable hydrodynamics of Toda chain: case of small systems
Authors: Kundu Aritra
Published: May 2023

Passing from a microscopic discrete lattice system with many degrees of freedom to a mesoscopic continuum system described by a few coarse-grained equations is challenging. The common folklore is to take the thermodynamic limit so that the physics of the discrete lattice describes the continuum results. The analytical procedure to do so relies on defining a small length scale (typically the lattice spacing) to coarse grain the microscopic evolution equations. Moving from the microscopic scale to the mesoscopic scale then requires careful approximations. In this work, we numerically test the coarsening in a Toda chain, which is an interacting integrable system, i.e., a system with a macroscopic number of conserved charges. Specifically, we study the spreading of fluctuations by computing the spatio-temporal thermal correlations with three different methods: (a) using microscopic molecular dynamics simulation with a large number of particles; (b) solving the generalized hydrodynamics equation; (c) solving the linear Euler scale equations for each conserved quantities. Surprisingly, the results for the small systems (c) match the thermodynamic results in (a) and (b) for macroscopic systems. This reiterates the importance and validity of integrable hydrodynamics in describing experiments in the laboratory, where we typically have microscopic systems.
Trust Is Not Enough: Accuracy, Error, Randomness, and Accountability in an Algorithmic Society
Authors: Moss Emanuel
Published: May 2023

Searching for improved algorithmic accountability.
Taking Flight with Copilot
Authors: Bird Christian , Ford Denae , Zimmermann Thomas , Forsgren Nicole , Kalliamvakou Eirini , Lowdermilk Travis , Gazit Idan
Published: May 2023

Early insights and opportunities of AI-powered pair-programming tools.
Better Algorithms through Faster Math
Authors: Greengard Samuel
Published: May 2023

The search for new algorithms that could reduce the time needed for multiplication is now at the center of data science.
FoundationDB: A Distributed Key-Value Store
Authors: Zhou Jingyu , Xu Meng , Shraer Alexander , Namasivayam Bala , Miller Alex , Tschannen Evan , Atherton Steve , Beamon Andrew J. , Sears Rusty , Leach John , Rosenthal Dave , Dong Xin , Wilson Will , Collins Ben , Scherer David , Grieser Alec , Liu Yang , Moore Alvin , Muppana Bhaskar , Su Xiaoge , Yadav Vishesh
Published: May 2023

FoundationDB is an open-source transactional key-value store created more than 10 years ago. It is one of the first systems to combine the flexibility and scalability of NoSQL architectures with the power of ACID transactions. FoundationDB adopts an unbundled architecture that decouples an in-memory transaction management system, a distributed storage system, and a built-in distributed configuration system. Each sub-system can be independently provisioned and configured to achieve scalability, high availability, and fault tolerance. FoundationDB includes a deterministic simulation framework, used to test every new feature under a myriad of possible faults. This rigorous testing makes FoundationDB extremely stable and allows developers to introduce and release new features in a rapid cadence. FoundationDB offers a minimal and carefully chosen feature set, which has enabled a range of disparate systems to be built as layers on top. FoundationDB is the underpinning of cloud infrastructure at Apple, Snowflake, and other companies, due to its consistency, robustness, and availability for storing user data, system metadata and configuration, and other critical information.
Can Generative AI Bots Be Trusted?
Authors: Denning Peter J.
Published: May 2023

It will be a long road to learning how to use generative AI wisely.
Conjoined Twins: Artificial Intelligence and the Invention of Computer Science
Authors: Haigh Thomas
Published: May 2023

How artificial intelligence and computer science grew up together.
In Memoriam: William A. Wulf
Authors: Garfinkel Simson L. , Spafford Eugene H.
Published: May 2023

Computing pioneer and ACM Fellow William A. Wulf died on March 10, 2023, in Charlottesville, VA, USA. He was 83.
You Don't know Jack about Application Performance
Authors: Collier-Brown David
Published: May 2023

You don't need to do a full-scale benchmark any time you have a performance or capacity planning problem. A simple measurement will provide the bottleneck point of your system: This example program will get significantly slower after eight requests per second per CPU. That's often enough to tell you the most important thing: if you're going to fail.
SearchAuth: Neural Architecture Search-based Continuous Authentication Using Auto Augmentation Search
Authors: Li Yantao , Luo Jiaxing , Deng Shaojiang , Zhou Gang
Published: May 2023

Mobile devices have been playing significant roles in our daily lives, which has made device security and privacy protection extremely important. These mobile devices storing user sensitive and private information, therefore, need rigorous user authentication mechanisms. In this article, we present SearchAuth, a novel continuous authentication system on smartphones exploiting a neural architecture search (NAS) to find an optimal network architecture and an auto augmentation search (AAS) to more effectively train the optimal network along with the best data augmentation policies, by leveraging the accelerometer, gyroscope, and magnetometer on smartphones to capture users’ behavioral patterns. Specifically, SearchAuth consists of three stages, i.e., the offline stage, registration stage, and authentication stage. In the offline stage, we utilize the NAS on sensor data of the accelerometer, gyroscope, and magnetometer to find an optimal network architecture based on the designed search space. With the optimal network architecture, namely, NAS-based model, the AAS automatically optimizes the augmentation of the input data for more effectively training the model that is for feature extraction. In the registration stage, we use the trained NAS-based model to learn and extract deep features from the legitimate user’s data, and train the LOF classifier with 55 features selected by the PCA. In the authentication stage, with the well-trained NAS-based model and LOF classifier, SearchAuth identifies the current user as a legitimate user or an impostor when the user starts operating a smartphone. Based on our dataset, we evaluate the performance of the proposed SearchAuth, and the experimental results demonstrate that SearchAuth surpasses the representative authentication schemes by achieving the best accuracy of 93.95%, F1-score of 94.30%, and EER of 5.30% on the LOF classifier with dataset size of 100.
“Turning up the heat”: role of neurotrophic batokines in the postnatal maturation and remodeling of brown adipose tissue in deer mice
Authors: Robertson C. E. , Weaver F. E. , Nurse C. A.
Published: May 2023

In altricial Peromyscus mice, the developmental shift to endothermy accompanies the establishment of the brown adipose tissue sympathetic neural network. Cultured slices of neonatal BAT secreted high quantities of two predicted neurotrophic batokines: S100b and neuregulin-4, but surprisingly low levels of the classic neurotrophic factor, NGF. Despite low NGF, neonatal BAT-conditioned media was highly neurotrophic. Cold-exposed adults use all three factors to dramatically remodel BAT, suggesting that BAT-neuron communication is life-stage dependent.
[Retracted] POU Class 2 Associating Factor 1 Exerts a Protective Effect on the Respiratory Syncytial Virus‐Induced Acute Bronchiolitis by the NF‐κB Pathway
Authors: Zhang Liwen , Huang Zhiying , Wang Fei , Xue Mei , Zhang Xiaoyu , Wan Yu , Ma Liang
Published: May 2023

Background. Respiratory syncytial virus (RSV) is the main pathogen causing acute bronchiolitis, which is common in infants and young children. A previous study revealed the possible involvement of POU class 2 associating factor 1 (POU2AF1) in RSV‐triggered acute bronchiolitis. We attempted to clarify the specific action mechanism of POU2AF1 underlying RSV‐triggered inflammation. Methods. RT‐qPCR measured POU2AF1 levels in RSV‐infected children, mice, and airway epithelial cell lines (HBECs). HE staining showed histopathological features in the lung tissue of RSV‐infected mice. ELISA examined the contents of proinflammatory cytokines in RSV‐infected mice. Western blotting evaluated the protein abundance of proinflammatory cytokines in RSV‐infected HBECs and assessed NF‐κB pathway‐associated protein expression in RSV‐infected mice and RSV‐treated HBECs. Results. POU2AF1 presented depletion in RSV‐infected children, mice, and HBECs. RSV‐infected triggered lung injury and inflammatory cell infiltration in the mouse lung tissue, while POU2AF1 overexpression rescued these changes. RSV‐infected induced inflammatory impairment in HBECs, whereas POU2AF1 reversed this effect. POU2AF1 suppressed the upregulated NF‐κB pathway‐associated protein expression in mice and HBECs under RSV infection. Conclusion. POU2AF1 exerts a protective impact on RSV‐induced acute bronchiolitis in vitro and in vivo through the NF‐κB pathway. Our research may provide a novel direction for better therapy of RSV‐triggered acute bronchiolitis.
Mixed Lump-Stripe Soliton Solutions to a New Extended Jimbo-Miwa Equation
Authors: He Yinghui
Published: May 2023

In this paper, the localized properties of lump and interaction solutions to a new extended Jimbo-Miwa (EJM) equation are studied. Based on the Hirota bilinear method and the test function method, the exact solutions of the EJM equation are discussed; the lump soliton solution, lump-kink soliton solution, and periodic lump solution are obtained. Furthermore, the dynamic properties of the obtained solutions are also discussed by graphical simulation. As far as we know, the obtained results have not been reported.
Flexibility Pricing of Grid-Connected Energy Hubs in the Presence of Uncertain Energy Resources
Authors: Hamrahi Mousa , Mallaki Mehrdad , Pirkolachahi Naghi Moaddabi , Shirazi Najme Cheraghi
Published: May 2023

The paper expresses the problem of flexibility pricing in energy hubs (EHs) that are in connection with electricity, heat, and gas networks considering of uncertain energy generation sources. Scheme includes a bilevel formulation. Its upper-level states for modeling of the flexibility services are provided by various resources within the EH. The problem considers maximization of the expected profit of these resources in the flexibility market. The problem constraints include the flexibility model of flexible resources such as storage devices, responsive loads, and controllable distributed generations (DGs). The flexibility model of resources relies on their active and heat power. The lower-level problem calculates energy and flexibility prices and formulates the flexible operation of energy resources considering EHs. Here, constraints include optimal power flow equations in the energy networks; operation model of EHs with power sources, storage devices, and different responsive loads; and flexibility limits of EHs. Also, a linear approximation model is adopted in the suggested design using conventional linearization techniques. Next, the Karush–Kuhn–Tucker (KKT) method is used to derive a single-level model for the problem. The scheme adopts scenario-based stochastic programming (SBSP) so that uncertainties of renewable power, energy price, load, and energy consumption of mobile storage devices are properly modeled. Finally, the results validate the suggested design’s potential in modifying and enhancing the operation, flexibility, and economic situation of energy networks and EHs.
STGNN-FAM: A Traffic Flow Prediction Model for Spatiotemporal Graph Networks Based on Fusion of Attention Mechanisms
Authors: Qi Xueying , Hu Weijian , Li Baoshan , Han Ke
Published: May 2023

Network traffic state prediction has been constantly challenged by complex spatiotemporal features of traffic information as well as imperfection in streaming data. This paper proposes a traffic flow prediction model for spatiotemporal graph networks based on fusion of attention mechanisms (STGNN-FAM) to simultaneously tackle these challenges. This model contains a spatial feature extraction layer, a bidirectional temporal feature extraction layer, and an attention fusion layer, which not only fully considers the temporal and spatial features of the traffic flow problem but also uses the attention mechanism to enhance the critical temporal and spatial features to achieve more accurate and robust predictions. Experimental results on a network traffic speed dataset PeMSD7 show that the proposed STGNN-FAM outperforms several important benchmarks in prediction accuracy and the ability to withstand interference in the data stream, especially for mid- and long-term prediction of 30 minutes and 45 minutes.
Supplementary Table S3 from Circulating Sex Hormone Levels and Risk of Gastrointestinal Cancer: Systematic Review and Meta-Analysis of Prospective Studies
Authors: Liu Zhiqiang , Zhang Yingfan , Lagergren Jesper , Li Shanshan , Li Jingru , Zhou Zhixian , Hu Zhijian , Xie Shao-Hua
Published: May 2023

Supplementary Table S3 shows Newcastle-Ottawa Scale of included studies.