bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue evolution and properties of plasma solid-state surface metallurgical TiCoCrNiWMo high-entropy alloy coatings
Authors: Li Xin , Zhou Zixiang , Wang Chenglei , Qin Haiqing , Yang Jijie , Liu Weijie , Liang Mulin , Liu Chong , Tan Hong , Zhang Zhenjun
Published: September 2023

Using plasma solid-state surface metallurgy is a new method for preparing high-entropy alloy (HEA) coatings. In this paper, based on the experience in plasma solid-state surface metallurgy and the HEA, the TiCoCrNiWMo HEA coatings with metallurgical bonding and gradient structure were prepared by five-element co-infiltration of Co–Cr–Ni–W–Mo on the surface of a TC4 substrate for the first time. The tissue morphology evolution and properties of HEA coatings at different holding temperatures were investigated. The results show that the HEA coating at the holding temperature of 1000 °C consists of a deposited layer + diffusion layer. When the temperature exceeds the (α + β)/β transition temperature of TC4, only the deposited layer is formed on the surface of the substrate. Holding temperature does not affect the phase composition of the HEA coating. The best bonding performance of the HEA coating with the substrate was achieved at a holding temperature of 1000 °C, with a bonding force of about 63.81 N. All the HEA coatings showed different degrees of improvement in hardness, wear resistance, and corrosion resistance compared to the substrate. The HEA coatings prepared at 1000 °C had the best performance, with hardness and wear resistance 1.5 and 8.9 times higher than those of the substrate, respectively, and excellent corrosion resistance in acidic, alkaline, and salt solutions. The results show that the new TiCoCrNiWMo HEA coatings prepared by plasma solid-state surface metallurgy have good wear resistance and corrosion resistance and have good application prospects in the fields of automobile manufacturing and shipbuilding.
Numerical and experimental investigation of a variable-curvature shell class I flextensional transducer
Authors: Li Depeng , Lan Yu , Zhou Tianfang
Published: September 2023

Class I flextensional transducers cannot form broadband characteristics because of the deep valley between their first- and second-order response curves. This valley arises from the sound pressure cancellation produced by the vibration in different areas of the shell. This paper examines the cause of the deep valley by analyzing the three-dimensional equivalent radiated sound field of the transducer. By solving the three-dimensional vibration equation of the shell of revolution and reducing its dimensionality, it can be concluded that its vibration state is related to the positive and negative curvatures in both main directions. Therefore, a variable-curvature shell class I flextensional transducer is proposed, and the second-order vibration of the transducer is changed by the variable-curvature structure composed of positive and negative Gaussian curvature surfaces. The proposed transducer avoids sound pressure cancellation and achieves broadband characteristics. After optimization, a transducer prototype is fabricated, and a pool test is conducted. The test results show that the transducer couples the first three vibration modes, attaining broadband characteristics with an in-band fluctuation of less than 8 dB and a bandwidth of more than 5.4 kHz in the axial and circumferential directions.
The Influence of Menstrual-Cycle Phase on Measures of Recovery Status in Endurance Athletes: The Female Endurance Athlete Project
Authors: De Martin Topranin Virginia , Engseth Tina Pettersen , Hrozanova Maria , Taylor Madison , Sandbakk Øyvind , Noordhof Dionne A.
Published: September 2023

Purpose: To investigate the influence of menstrual-cycle (MC) phase on measures of recovery status, that is, resting heart rate, perceived sleep quality, and physical and mental readiness to train, among female endurance athletes. Methods: Daily data were recorded during 1 to 4 MCs (ie, duration ≥21 and ≤35 d, ovulatory, luteal phase ≥10 d) of 41 trained-to-elite-level female endurance athletes (mean [SD]: age 27 [8] y, weekly training: 9 [3] h). Resting heart rate was assessed daily using a standardized protocol, while perceived sleep quality and physical and mental readiness to train were assessed using a visual analog scale (1–10). Four MC phases (early follicular phase [EFP], late follicular phase, ovulatory phase, and midluteal phase [MLP]) were determined using the calendar-based counting method and urinary ovulation-prediction test. Data were analyzed using linear mixed-effects models. Results: Resting heart rate was significantly higher in MLP (1.7 beats·min−1, P = .006) compared with EFP without significant differences between the other MC phases. Perceived sleep quality was impaired in MLP compared with late follicular phase (−0.3, P = .035). Physical readiness to train was lower both in ovulatory phase (−0.6, P = .015) and MLP (−0.5, P = .026) compared with EFP. Mental readiness to train did not show any significant differences between MC phases (P > .05). Conclusions: Although significant, the findings had negligible to small effect sizes, indicating that MC phase is likely not the main determinant of changes in measures of recovery status but, rather, one of the many possible stressors.
Opposing roles of RUBCN isoforms in autophagy and memory B cell generation
Authors: Tsai Chao-Yuan , Sakakibara Shuhei , Kuan Yu-Diao , Omori Hiroko , El Hussien Maruwa Ali , Okuzaki Daisuke , Lu Shiou-Ling , Noda Takeshi , Tabata Keisuke , Nakamura Shuhei , Yoshimori Tamotsu , Kikutani Hitoshi
Published: September 2023

RUBCN (also known as Rubicon) was originally identified as a negative regulator of autophagy, a process by which cells degrade and recycle damaged components or organelles and that requires the activity of the class III PI3K VPS34 and the mTORC1 protein complex. Here, we characterized the role of a shorter isoform, RUBCN
100
, as an autophagy-promoting factor in B cells. RUBCN
100
was translated from alternative translation initiation sites and lacked the RUN domain of the longer, previously characterized RUBCN
130
isoform. Specific deficiency of RUBCN
130
in B cells enhanced autophagy, which promoted memory B cell generation. In contrast to RUBCN
130
, which is localized in late endosomes and lysosomes and suppresses the enzymatic activity of VPS34, an effect thought to mediated by its RUN domain, RUBCN
100
was preferentially located in early endosomes and enhanced VPS34 activity, presumably because of the absence of the RUN domain. Furthermore, RUBCN
100
, but not RUBCN
130
, enhanced autophagy and suppressed mTORC1 activation. Our findings reveal that the opposing roles of two RUBCN isoforms are critical for autophagy regulation and memory B cell differentiation.
The lncRNA MIR99AHG directs alternative splicing of
SMARCA1
by PTBP1 to enable invadopodia formation in colorectal cancer cells
Authors: Li Danxiu , Wang Xin , Miao Hui , Liu Hao , Pang Maogui , Guo Hao , Ge Minghui , Glass Sarah E. , Emmrich Stephan , Ji Songtao , Zhou Yun , Ye Xiaoni , Mao Huajie , Wang Jing , Liu Qi , Kim Taewan , Klusmann Jan-Henning , Li Cunxi , Liu Zhenxiong , Jin Haifeng , Nie Yongzhan , Wu Kaichun , Fan Daiming , Song Xu , Wang Xin , Li Ling , Lu Yuanyuan , Zhao Xiaodi
Published: September 2023

Alternative splicing regulates gene expression and functional diversity and is often dysregulated in human cancers. Here, we discovered that the long noncoding RNA (lncRNA) MIR99AHG regulated alternative splicing to alter the activity of a chromatin remodeler and promote metastatic behaviors in colorectal cancer (CRC). MIR99AHG was abundant in invasive CRC cells and metastatic tumors from patients and promoted motility and invasion in cultured CRC cells. MIR99AHG bound to and stabilized the RNA splicing factor PTBP1, and this complex increased cassette exon inclusion in the mRNA encoding the chromatin remodeling gene
SMARCA1
. Specifically, MIR99AHG altered the nature of PTBP1 binding to the splice sites on intron 12 of
SMARCA1
pre-mRNA, thereby triggering a splicing switch from skipping to including exon 13 to produce the long isoform, SMARCA1-L. SMARCA1, but not SMARCA1-L, suppressed invadopodia formation, cell migration, and invasion. Analysis of CRC samples revealed that the abundance of
MIR99AHG
transcript positively correlated with that of
SMARCA1-L
mRNA and PTBP1 protein and with poor prognosis in patients with CRC. Furthermore, TGF-β1 secretion from cancer-associated fibroblasts increased
MIR99AHG
expression in CRC cells. Our findings identify an lncRNA that is induced by cues from the tumor microenvironment and that interacts with PTBP1 to regulate alternative splicing, potentially providing a therapeutic target and predictive biomarker for metastatic CRC.
Simultaneous carbon catabolite repression governs sugar and aromatic co-utilization in
Pseudomonas putida
M2
Authors: Shrestha Shilva , Awasthi Deepika , Chen Yan , Gin Jennifer , Petzold Christopher J. , Adams Paul D. , Simmons Blake A. , Singer Steven W.
Published: September 2023

Pseudomonas putida
have emerged as promising biocatalysts for the conversion of sugars and aromatic compounds obtained from lignocellulosic biomass. Understanding the role of carbon catabolite repression (CCR) in these strains is critical to optimize biomass conversion to fuels and chemicals. The CCR functioning in
P. putida
M2, a strain capable of consuming both hexose and pentose sugars as well as aromatic compounds, was investigated by cultivation experiments, proteomics, and CRISPRi-based gene repression. Strain M2 co-utilized sugars and aromatic compounds simultaneously; however, during cultivation with glucose and aromatic compounds (
p-
coumarate and ferulate) mixture, intermediates (4-hydroxybenzoate and vanillate) accumulated, and substrate consumption was incomplete. In contrast, xylose-aromatic consumption resulted in transient intermediate accumulation and complete aromatic consumption, while xylose was incompletely consumed. Proteomics analysis revealed that glucose exerted stronger repression than xylose on the aromatic catabolic proteins. Key glucose (Eda) and xylose (XylX) catabolic proteins were also identified at lower abundance during cultivation with aromatic compounds implying simultaneous catabolite repression by sugars and aromatic compounds. Reduction of
crc
expression via CRISPRi led to faster growth and glucose and
p
-coumarate uptake in the CRISPRi strains compared to the control, while no difference was observed on xylose+
p
-coumarate. The increased abundances of Eda and amino acid biosynthesis proteins in the CRISPRi strain further supported these observations. Lastly, small RNAs (sRNAs) sequencing results showed that CrcY and CrcZ homologues levels in M2, previously identified in
P. putida
strains, were lower under strong CCR (glucose+
p
-coumarate) condition compared to when repression was absent (
p
-coumarate or glucose only).

IMPORTANCE

A newly isolated
Pseudomonas putida
strain,
P. putida
M2, can utilize both hexose and pentose sugars as well as aromatic compounds making it a promising host for the valorization of lignocellulosic biomass. Pseudomonads have developed a regulatory strategy, carbon catabolite repression, to control the assimilation of carbon sources in the environment. Carbon catabolite repression may impede the simultaneous and complete metabolism of sugars and aromatic compounds present in lignocellulosic biomass and hinder the development of an efficient industrial biocatalyst. This study provides insight into the cellular physiology and proteome during mixed-substrate utilization in
P. putida
M2. The phenotypic and proteomics results demonstrated simultaneous catabolite repression in the sugar-aromatic mixtures, while the CRISPRi and sRNA sequencing demonstrated the potential role of the
crc
gene and small RNAs in carbon catabolite repression.
Inactivation of the Sts enzymes promotes resistance to lethal
Staphylococcus aureus
infection
Authors: Zaman Anika , Diago Navarro Elizabeth , Fries Bettina C. , Kim Hwan Keun , Carpino Nick
Published: September 2023

Staphylococcus aureus
is a highly infective Gram-positive bacterial pathogen that causes a wide range of diseases in both healthy and immunocompromised individuals. It can evade host immune defenses by expressing numerous virulence factors and toxins. Coupled with the inability of the human host to develop protective immunity against
S. aureus
, the emergence of antibiotic-resistant strains complicates treatment options. The non-canonical Sts phosphatases negatively regulate signaling pathways in varied immune cell types. To determine the role of the Sts proteins in regulating host responses to a Gram-positive microorganism, we investigated the response of mice lacking Sts expression to
S. aureus
infection. Herein, we demonstrate that
Sts
−/−
animals are significantly resistant to lethal intravenous doses of
S. aureus
strain USA300. Resistance is characterized by significantly enhanced survival and accelerated bacterial clearance in multiple peripheral organs. Infected
Sts
−/−
animals do not display increased levels of cytokines TNFα, IFNγ, and IL-6 in the spleen, liver, and kidney during the early stages of the infection, suggesting that a heightened pro-inflammatory response does not underlie the resistance phenotype.
In vivo
ablation of mononuclear phagocytes compromises the
Sts
−/−
enhanced CFU clearance phenotype. Additionally,
Sts
−/−
bone marrow-derived macrophages demonstrate significantly enhanced restriction of intracellular
S. aureus
following
ex vivo
infection. These results reveal the Sts enzymes to be critical regulators of host immunity to a virulent Gram-positive pathogen and identify them as therapeutic targets for optimizing host anti-microbial responses.
Supplemental Material: Origins and evolution of two types of Late Triassic granitic magmas in the Caolong-Xiangkariwa area of central-eastern Songpan-Ganze terrane, northern Tibet: Implications for pegmatite lithium mineralization
Authors: Liu Jin-Heng , WANG QIANG , et al.
Published: September 2023

Supplemental figures, analytical methods, analytical data, and supplemental references.
National Genomic Information Database
Authors: Kolesnikov I. A. , Nikolenko M. V. , Ermakov A. V. , Korzhenkov A. A. , Zaikin A. A. , Velikhov V. E. , Bobkov S. A. , Sharko F. S. , Namsaraev Z. B. , Patrushev M. V.
Published: September 2023

In accordance with the order of the President of the Russian Federation, the National Research Center “Kurchatov Institute” is creating the National Genomic Information Database (NGID). According to the amendments to Federal Law dated December 29, 2022, it is mandatory for organizations involved in genetic engineering and the production or supply of genetically engineered organisms or products obtained with their use to deposit information in the NGID. It is planned that the NGID will become a key element of the infrastructure for genetic research and development in Russia, providing the storage, integration, and analysis of genetic data. This article provides information on the computational and networking infrastructure, software, data storage, and analytical capabilities of the NGID.
Perspectives of extremely prematurely born adults on what to consider in prenatal decision-making: a qualitative focus group study
Authors: de Boer Angret , De Proost Lien , de Vries Marieke , Hogeveen Marije , Verweij E J T (Joanne) , Geurtzen Rosa
Published: September 2023

Objective

A shared decision-making (SDM) approach is recommended for prenatal decisions at the limit of viability, with a guiding role for parental values. People born extremely premature experience the consequences of the decision made, but information about their perspectives on prenatal decisions is lacking. Therefore, this study aims to describe their perspectives on what is important in decision-making at the limit of viability.

Design

Semi-structured focus group discussions were conducted, recorded and transcribed verbatim. The data were independently analysed by two researchers in Atlas.ti.

Results

Four focus groups were conducted in the Netherlands, with five to six participants each, born between 240/7and 300/7weeks gestation in the period between 1965 and 2002. Considering their personal life experiences and how their extremely premature birth affected their families, the participants reflected on decision-making at the limit of viability. Various considerations were discussed and summarised into the following themes: anticipated parental regret, the wish to look at the baby directly after birth, to give the infant a chance at survival, quality of life, long-term outcomes for the infant and the family, and religious or spiritual considerations.

Conclusions

Insights into the perspectives of adults born extremely premature deepened our understanding of values considered in decision-making at the limit of viability. Results point out the need for a more individualised prediction of the prognosis and more extensive information on the lifelong impact of an extremely premature birth on both the infant and the family. This could help future parents and healthcare professionals in value-laden decision-making.
Axial length elongation profiles from 3 to 6 years in an Asian paediatric population: the Growing Up in Singapore Towards Healthy Outcomes birth cohort study (GUSTO)
Authors: Chen David Ziyou , Wong Charlene , Lam Janice Sing Harn , Sun Chen-Hsin , Lai Yien , Koh Victor Teck Chang , Chong Yap-Seng , Saw Seang-Mei , Tham Yih-Chung , Ngo Cheryl
Published: September 2023

Aims

To determine axial length (AL) elongation profiles in children aged 3–6 years in an Asian population.

Methods

Eligible subjects were recruited from the Growing Up in Singapore Towards Healthy Outcomes birth cohort. AL measurement was performed using IOLMaster (Carl Zeiss Meditec, Jena, Germany) at 3 and 6 years. Anthropometric measurements at birth, cycloplegic refraction at 3 and 6 years, questionnaires on the children’s behavioural habits at 2 years and parental spherical equivalent refraction were performed. Multivariable linear regression model with generalised estimating equation was performed to determine factors associated with AL elongation.

Results

273 eyes of 194 children were included. The mean AL increased from 21.72±0.59 mm at 3 years to 22.52±0.66 mm at 6 years (p<0.001). Myopic eyes at 6 years had greater AL elongation (1.02±0.34 mm) compared with emmetropic eyes (0.85±0.25 mm, p=0.008) and hyperopic eyes (0.74±0.16 mm, p<0.001). The 95th percentile limit of AL elongation was 1.59 mm in myopes, 1.34 mm in emmetropes and 1.00 mm in hyperopes. Greater birth weight (per 100 g, β=0.010, p=0.02) was significantly associated with greater AL elongation from 3 to 6 years, while parental and other behavioural factors assessed at 2 years were not (all p≥0.08).

Conclusion

In this preschool cohort, AL elongates at an average length of 0.80 mm from 3 to 6 years, with myopes demonstrating the greatest elongation. The differences in 95th percentile limits for AL elongation between myopes, emmetropes and hyperopes can be valuable information in identifying myopia development in preschool children.
Pharmacists’ approach to oncology medicine shortages: results of a cross-sectional survey in Pakistan
Authors: Shukar Sundus , Shahid Muhammad Hassaan , Zhang Jinwei , Din Shayan Muhammad , Khan Faiz Ullah , Fang Yu , Yang Caijun
Published: September 2023

Objectives

The study estimated the shortages of oncology medicines in Pakistan, their causes, impacts, mitigation strategies, and possible interventions.

Design

Cross-sectional survey.

Setting

Oncology pharmacists working at 43 oncology settings (out of 80) from five regions of Pakistan (four provinces (Punjab, Sindh, Khyber Pakhtunkhwa and Baluchistan) and one federal territory (Islamabad)) were approached.

Participants

Oncology pharmacists with more than 1 year of experience were selected using stratified random sampling, and data were collected using a questionnaire from September 2021 to January 2022.

Primary and secondary outcome measures

To estimate the prevalence of oncology medicine shortages in Pakistan and establish recommendations to overcome them.

Results

Of 167 responded pharmacists, 87% experienced shortages in their practice. Most respondents (50%) experienced both oncology and support agent shortages. It was a current problem in hospitals (58%) and increased with time, but the situation varied across regions (p=0.007). Mainly shortages occur half-yearly (p=0.001) and last for <3 months. Injectable (56.8%) and branded drugs (44.9%) were short. The most frequently mentioned drugs affected by shortages were etoposide, paclitaxel, dacarbazine, bleomycin and carboplatin. Usually, distributors (51.5%) notify the pharmacists about the shortages, and federal agencies (36%) are responsible for these shortages. Distributors (53.4%) were the main source of supply, and shortages were encountered by them as well. The impacts included delayed care (25%) and suboptimal outcomes (23%) on patients, extra time (32%) for staff, prioritisation issues (31%) for pharmacists, delayed clinical trials (60.5%) and increased drugs prices (52.1%). Some hospitals have reporting systems (39.5%) and recording (29.3%) drug shortages. The shortages were managed using available alternative options (21%) and redistributing (21%) the currently available stock.

Conclusion

Pakistan’s healthcare system is affected by oncology medicine shortages. The government should establish a cancer registry and drug shortage platform, revise drug prescribing/pricing policies and practice penalties for breaching regulations. Oncology medicines must be widely available to avoid the grey market.
Association between Johns Hopkins Adjusted Clinical Groups risk scores and self-reported outcome measures: an observational study among individuals with complex or long-term conditions in Norway
Authors: Hosar Rannei , Steinsbekk Aslak
Published: September 2023

Objective

Investigate the association between Johns Hopkins Adjusted Clinical Groups (ACG) risk scores and low scores in self-reported outcome measures (SROMs) among individuals with complex or long-term conditions.

Design

Longitudinal study using five ACG risk scores based on diagnoses from general practitioner (GP) visits in 1 year and responses to a survey including three SROMs 4 months later.

Setting

Four adjacent municipalities in Central Norway.

Participants

Non-institutionalised individuals ≥18 years with ≥1 diagnosis code indicating a complex or long-term condition, ≥1 visit to a GP, and who participated in the survey (n=2944).

Measures

Dependent variables were low scores in the three SROMs (threshold for being defined as a low score in parentheses): Patient Activation Measure (level 1–2), EQ-5D (<0.4) or self-rated health (‘Poor’). Independent variables were five ACG variables.

Results

The individuals with the lowest scores in the three SROMs were mostly three separate groups. The lowest Patient Activation Measure scores were associated with high scores in the ACG variables unscaled total cost predicted risk (adjusted odds ratio (adjOR) 1.80) and positive frailty flag (adjOR 1.76). The lowest EQ-5D scores were associated with high scores in the ACG variables unscaled concurrent risk (adjOR 1.60) and probability persistent high user scores (adjOR 2.83). The lowest self-rated health scores were associated with high scores in the ACG variable unscaled concurrent risk scores (adjOR 1.77), unscaled total cost predicted risk scores (adjOR 2.14) and receiving a positive frailty flag (adjOR 1.82).

Conclusions

There were associations between ACG risk scores and subsequent low SROM scores. This suggests a potential to use diagnosis-based risk stratification systems as a proxy for SROMs to identify individuals with complex or long-term conditions for person-centred healthcare intervention.
Protocol for a double-blinded randomised controlled trial investigating the use of adjunct bicarbonate in carpal tunnel release: a single-centre study
Authors: Hytönen Mikael , Nietosvaara Yrjänä , Reito Aleksi , Sirola Joonas , Heikkinen Noora , Savolainen Aukusti , Räisänen Mikko P
Published: September 2023

Introduction

This study aims to compare the effectiveness of buffered and non-buffered long-acting local anaesthetics in pain relief during and after carpal tunnel release (CTR) surgery. Carpal tunnel syndrome (CTS) is the most common peripheral nerve entrapment syndrome. Surgical treatment of CTS, CTR, is the most common hand surgical operation. CTR is usually performed under local anaesthesia, the application of which is often the most painful event during the procedure. One important aspect of patient satisfaction is adequate pain management during and after CTR. Long-acting local anaesthetics provide good postoperative pain control. Adjunct bicarbonate has been shown to reduce pain during injection of local anaesthetic and to prolong its analgesic effect. To date, no published randomised controlled trial has compared buffered to non-buffered long-acting local anaesthetic during CTR.

Methods and analysis

The study will randomly assign 116 patients with CTS to receive buffered or non-buffered mixtures of lidocaine and bupivacaine with epinephrine before CTR. The primary outcome is overall pain experienced during the injection of local anaesthetic, assessed with the Visual Analogue Scale. The secondary outcomes are pain intensity from the injection and during CTR, use of painkillers and pain intensity every 4 hours until third postoperative night, symptom severity and functional status preoperatively and at 3 months after surgery, and patient-rated outcome measures at 3 months after surgery.

Ethics and dissemination

This protocol was approved by the Research Ethics Committee of the Northern Savo Hospital District (2311/2021). The study will be performed according to the principles of good clinical practice and the Declaration of Helsinki. The results are expected to be presented in an international hand surgical conference and the manuscript to be sent to a hand surgery-orientated peer-reviewed journal during 2024.

Trial registration number

This study is registered to clinicaltrials.gov, study IDNCT05328180.
Effects of PCSK9 inhibitors on coronary microcirculation, inflammation and cardiac function in patients with CHD after PCI: a protocol for systematic review and meta-analysis
Authors: Ye Xuejiao , Wang Shihan , Liu Xiao’an , Wu Qian , Lv Yanfei , Lv Qianyu , Li Junjia , Li Lanlan , Yang Yingtian
Published: September 2023

Introduction

Coronary heart disease (CHD) is one of the common cardiovascular diseases that seriously jeopardise human health, and endothelial inflammation and dyslipidaemia are the initiating links leading to its occurrence. Percutaneous coronary intervention (PCI) is one of the most effective surgical treatments for CHD with narrowed or blocked blood vessels, which can quickly unblock the blocked vessels and restore coronary blood supply. However, most patients may experience coronary microcirculation disorders (CMDs) and decreased cardiac function after PCI treatment, which directly affects the efficacy of PCI and the prognosis of patients. Preprotein converting enzyme subtilisin/Kexin 9 (PCSK9) inhibitors are novel pleiotropy lipid-lowering drug with dual anti-inflammation and lipid-lowering effects, and represent a new clinical pathway for rapid correction of dyslipidaemia. Therefore, we designed this protocol to systematically evaluate the effects of PCSK9 inhibitors on coronary microcirculation and cardiac function in patients with CHD after PCI, and to provide high-quality evidence-based evidence for the clinical application of PCSK9 inhibitors.

Methods and analysis

This protocol is reported strictly in accordance with the 2020 Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols Guidelines. We will search PubMed, EMBASE, Web of Science and three Chinese databases (CNKI, Wanfang and VIP database) according to preset search strategies, without language and publication data restrictions. We will work with manual retrieval to screen references that have been included in the literature. Google Scholar will be used to search for grey literature. The final included literature must meet the established inclusion criteria. Titles, abstracts and full text will be extracted independently by two reviewers, and disagreements will be resolved through discussion or the involvement of a third reviewer. Extracted data will be analysed using Review Manager V.5.3. The Cochrane Risk of Bias Tool will be used to evaluate the risk of bias. Publication bias will be assessed by funnel plots. Heterogeneity will be assessed by I2test and subgroup analyses will be used to further investigate potential sources of heterogeneity. The quality of the literature will be assessed by GRADE score. This protocol will start in January 2026 and end in December 2030.

Ethics and dissemination

This study is a systematic review of published literature data and no special ethical approval was required.

PROSPERO registration number

CRD42022346189.
Ditching decision-making capacity
Authors: Fogal Daniel , Schwan Ben
Published: September 2023

Decision-making capacity (DMC) plays an important role in clinical practice—determining, on the basis of a patient’s decisional abilities, whether they are entitled to make their own medical decisions or whether a surrogate must be secured to participate in decisions on their behalf. As a result, it is critical that we get things right—that our conceptual framework be well-suited to the task of helping practitioners systematically sort through the relevant ethical considerations in a way that reliably and transparently delivers correct verdicts about who should and should not have the authority to make their own medical decisions. Unfortunately, however, the standard approach to DMC does not get things right. It is of virtually no help in identifying and clarifying the relevant ethical considerations. And, embedded in the prevailing anti-paternalist paradigm, DMC assessments obfuscate and distort the underlying ethical justification for granting or withholding decisional authority. Here, we describe the core commitments of the standard approach to DMC and then highlight three problems with it. We then argue that these problems are significant enough that they call for more than merely tinkering and fine-tuning; variations of the standard approach cannot adequately address them. Instead, we should ditch DMC.
Situations of moral injury and ambiguity will always go on in healthcare: it is how we deal with them that is important
Authors: Nurse Kim , Baird Hannah
Published: September 2023

The article explores the concepts of moral distress and moral injury experienced by healthcare professionals, from the perspective of two junior doctors, in the National Health Service. It highlights the daily challenges faced by doctors due to insufficient resources, staff shortages and time constraints, leading to an inability to provide the expected level of care, which if not addressed can result in long-term psychological harm and impaired functioning.
Resilience for freight transportation systems to disruptive events: a review of concepts and metrics
Authors: Patnala Phani Kumar , Regehr Jonathan D. , Mehran Babak , Regoui Chaouki
Published: September 2023

Resilience is a multidisciplinary concept that deals with rapid response and recovery of a system experiencing a disruption. Despite extensive research on this topic, there is a need to clarify resilience concepts in the context of road freight transportation systems (FTSs) from a three-dimensional perspective (i.e., physical infrastructure, users, and managing organizations) and to identify persistent knowledge gaps concerning the characterization and measurement of FTS resilience vis-à-vis disruptive events. This paper addresses these shortcomings through a systematic review of 149 research studies. The synthesis of findings clarifies inconsistencies associated with the characteristics of FTS resilience and in so doing, establishes a unified framework for measuring FTS resilience through the life cycle of disruptive events. Critical data gaps, methodological shortcomings, and a lack of empirical evidence concerning FTS resilience to disruptive events remain. More robust analytical approaches are required to incorporate interdependencies among FTS dimensions into resilience assessments.
Gravity imaging of sub-Zechstein geological structures in the UK sector of the North Sea using the gravity layer stripping method
Authors: Fairhead J. D. , Marsden D. , Azli N. M. , Özsöz İ. , Maxwell D. , Rose O. , Green C. M.
Published: September 2023

Extensive geophysical databases, covering the UK sector of the North Sea, have been used to gravity layer strip the sedimentary layers down to the base Zechstein so that the gravity response of the Carboniferous and deeper strata can be identified and structurally interpreted. To achieve this, the average bulk density grids for each layer were derived using Gardner's functions derived from well velocity and density logs. The resulting residual gravity response of each layer and the Moho response were then removed from the Free air gravity anomaly to generate the isostatic gravity response of the crust below the base Zechstein. This gravity response was used to re-evaluate the British Geological Survey interpretation over the Mid North Sea High (MNSH) and was able to identify the same crustal structures. Using the tilt derivative method, a positive gravity anomaly was found to parallel the central fracture zone that forms a northern extension of the Dowsing fault zone. This anomaly can be traced north across the MNSH with offsets coinciding with the WSW–ENE basement lineaments. To the south, the southern North Sea basin is well defined by the stratigraphic layer depth and thickness maps as well as the residual gravity maps which identify the structures associated with the low-density Carboniferous Coal Measures.
Anomalous facies of the Kinnesswood Formation in the Cumbraes Basin: a late Famennian playa complex in SW Scotland
Authors: Caldwell W. G. E. , Young G. M.
Published: September 2023

Among the important geological attributes of the small Cumbraes Basin in the southwestern off-shore Midland Valley of Scotland, the 4 km-long, fragmented but well-exposed section through the Devonian–Carboniferous boundary sequence in southern Great Cumbrae island ranks highly. In a continuous short stretch of the south and west coasts, large portions of this sequence are superbly preserved in tide-washed strandline surfaces and in old post-glacial sea cliff. This enhanced exposure leaves no doubt that the outcrops belong to two, immediately successive, members of the Kinnesswood Formation – the lower the Doughend Sandstone, the upper the Foul Port Mudstone – and that they provide some of the best available exposures on which to base description and interpretation. The facies of the fluviatile Doughend Sandstone shares many characteristics with the underlying Kelly Burn Sandstone of the Upper Old Red Sandstone, whereas that of the Foul Port Mudstone is distinct and unusual, attributed to local tectonics, influenced by movements on older and more major fractures such as the Highland Boundary Fault, with sediment accumulation taking place in a playa-lake complex of considerable extent.
Surrogate Lagrangian Relaxation: A Path to Retrain-Free Deep Neural Network Pruning
Authors: Zhou Shanglin , Bragin Mikhail A. , Gurevin Deniz , Pepin Lynn , Miao Fei , Ding Caiwen
Published: September 2023

Network pruning is a widely used technique to reduce computation cost and model size for deep neural networks. However, the typical three-stage pipeline (i.e., training, pruning, and retraining (fine-tuning)) significantly increases the overall training time. In this article, we develop a systematic weight-pruning optimization approach based on surrogate Lagrangian relaxation (SLR), which is tailored to overcome difficulties caused by the discrete nature of the weight-pruning problem. We further prove that our method ensures fast convergence of the model compression problem, and the convergence of the SLR is accelerated by using quadratic penalties. Model parameters obtained by SLR during the training phase are much closer to their optimal values as compared to those obtained by other state-of-the-art methods. We evaluate our method on image classification tasks using CIFAR-10 and ImageNet with state-of-the-art multi-layer perceptron based networks such as MLP-Mixer; attention-based networks such as Swin Transformer; and convolutional neural network based models such as VGG-16, ResNet-18, ResNet-50, ResNet-110, and MobileNetV2. We also evaluate object detection and segmentation tasks on COCO, the KITTI benchmark, and the TuSimple lane detection dataset using a variety of models. Experimental results demonstrate that our SLR-based weight-pruning optimization approach achieves a higher compression rate than state-of-the-art methods under the same accuracy requirement and also can achieve higher accuracy under the same compression rate requirement. Under classification tasks, our SLR approach converges to the desired accuracy × faster on both of the datasets. Under object detection and segmentation tasks, SLR also converges 2× faster to the desired accuracy. Further, our SLR achieves high model accuracy even at the hardpruning stage without retraining, which reduces the traditional three-stage pruning into a two-stage process. Given a limited budget of retraining epochs, our approach quickly recovers the model’s accuracy.
Understanding the Helpfulness of Stale Bot for Pull-Based Development: An Empirical Study of 20 Large Open-Source Projects
Authors: Khatoonabadi Sayedhassan , Costa Diego Elias , Mujahid Suhaib , Shihab Emad
Published: September 2023

Pull Requests (PRs) that are neither progressed nor resolved clutter the list of PRs, making it difficult for the maintainers to manage and prioritize unresolved PRs. To automatically track, follow up, and close such inactive PRs, Stale bot was introduced by GitHub. Despite its increasing adoption, there are ongoing debates on whether using Stale bot alleviates or exacerbates the problem of inactive PRs. To better understand if and how Stale bot helps projects in their pull-based development workflow, we perform an empirical study of 20 large and popular open source projects. We find that Stale bot can help deal with a backlog of unresolved PRs, as the projects closed more PRs within the first few months of adoption. Moreover, Stale bot can help improve the efficiency of the PR review process as the projects reviewed PRs that ended up merged and resolved PRs that ended up closed faster after the adoption. However, Stale bot can also negatively affect the contributors, as the projects experienced a considerable decrease in their number of active contributors after the adoption. Therefore, relying solely on Stale bot to deal with inactive PRs may lead to decreased community engagement and an increased probability of contributor abandonment.
Wave-CapNet: A Wavelet Neuron-based Wi-Fi Sensing Model for Human Identification
Authors: Zhou Zhiyi , Wang Lei , Lu Xinxin , Tian Yu , Fang Jian , Lu Bingxian
Published: September 2023

Gait is regarded as a unique feature for identifying people, and gait recognition is the basis of various customized services of the IoT. Unlike traditional techniques for identifying people, the Wi-Fi-based technique is unconstrained by illumination conditions and such that it eliminates the need for dense, specialized sensors and wearable devices. Although deep learning-based sensing models are conducive to the development of Wi-Fi-based identification, the latter technique relies on a large amount of data and requires a long training time, where this limits the scope of its use for identifying people. In this study, we propose a Wi-Fi sensing model called Wave-CapNet for human identification. We use data processing to eliminate errors in the raw data so that the model can extract the characteristics in channel state information (CSI). We also design a dedicated adaptive wavelet neural network to extract representative features from Wi-Fi signals with only a few epochs of training and a small number of parameters. Experiments show that it can identify human gait with an average accuracy of 99%. Moreover, it can achieve an average accuracy of 95% by using only 10% of the data and fewer than five epochs and outperforms state-of-the-art (SOTA) methods.
Unlocking the Complex Cell Biology of Coral–Dinoflagellate Symbiosis: A Model Systems Approach
Authors: Jacobovitz Marie R. , Hambleton Elizabeth A. , Guse Annika
Published: September 2023

Symbiotic interactions occur in all domains of life, providing organisms with resources to adapt to new habitats. A prime example is the endosymbiosis between corals and photosynthetic dinoflagellates. Eukaryotic dinoflagellate symbionts reside inside coral cells and transfer essential nutrients to their hosts, driving the productivity of the most biodiverse marine ecosystem. Recent advances in molecular and genomic characterization have revealed symbiosis-specific genes and mechanisms shared among symbiotic cnidarians. In this review, we focus on the cellular and molecular processes that underpin the interaction between symbiont and host. We discuss symbiont acquisition via phagocytosis, modulation of host innate immunity, symbiont integration into host cell metabolism, and nutrient exchange as a fundamental aspect of stable symbiotic associations. We emphasize the importance of using model systems to dissect the cellular complexity of endosymbiosis, which ultimately serves as the basis for understanding its ecology and capacity to adapt in the face of climate change.
High-Sensitivity Cardiac Troponin Assays: Ready for Prime Time!
Authors: Krychtiuk Konstantin A. , Newby L. Kristin
Published: September 2023

Rapid and accurate triage of patients presenting with chest pain to an emergency department (ED) is critical to prevent ED overcrowding and unnecessary resource use in individuals at low risk of acute myocardial infarction (AMI) and to efficiently and effectively guide patients at high risk to definite therapy. The use of biomarkers for rule-out or rule-in of suspected AMI has evolved substantially over the last several decades. Previously well-established biomarkers have been replaced by cardiac troponin (cTn). High-sensitivity cTn (hs-cTn) assays represent the newest generation of cTn assays and offer tremendous advantages, including improved sensitivity and precision. Still, implementation of these assays in the United States lags behind several other areas of the world. Within this educational review, we discuss the evolution of biomarker testing for detection of myocardial injury, address the specifics of hs-cTn assays and their recommended use within triage algorithms, and highlight potential challenges in their use. Ultimately, we focus on implementation strategies for hs-cTn assays, as they are now clearly ready for prime time.
Circadian Regulation of Drug Responses: Toward Sex-Specific and Personalized Chronotherapy
Authors: Lévi Francis A. , Okyar Alper , Hadadi Eva , Innominato Pasquale F. , Ballesta Annabelle
Published: September 2023

Today's challenge for precision medicine involves the integration of the impact of molecular clocks on drug pharmacokinetics, toxicity, and efficacy toward personalized chronotherapy. Meaningful improvements of tolerability and/or efficacy of medications through proper administration timing have been confirmed over the past decade for immunotherapy and chemotherapy against cancer, as well as for commonly used pharmacological agents in cardiovascular, metabolic, inflammatory, and neurological conditions. Experimental and human studies have recently revealed sexually dimorphic circadian drug responses. Dedicated randomized clinical trials should now aim to issue personalized circadian timing recommendations for daily medical practice, integrating innovative technologies for remote longitudinal monitoring of circadian metrics, statistical prediction of molecular clock function from single-timepoint biopsies, and multiscale biorhythmic mathematical modelling. Importantly, chronofit patients with a robust circadian function, who would benefit most from personalized chronotherapy, need to be identified. Conversely, nonchronofit patients could benefit from the emerging pharmacological class of chronobiotics targeting the circadian clock.
The Moral Psychology of Artificial Intelligence
Authors: Bonnefon Jean-François , Rahwan Iyad , Shariff Azim
Published: September 2023

Moral psychology was shaped around three categories of agents and patients: humans, other animals, and supernatural beings. Rapid progress in artificial intelligence has introduced a fourth category for our moral psychology to deal with: intelligent machines. Machines can perform as moral agents, making decisions that affect the outcomes of human patients or solving moral dilemmas without human supervision. Machines can be perceived as moral patients, whose outcomes can be affected by human decisions, with important consequences for human–machine cooperation. Machines can be moral proxies that human agents and patients send as their delegates to moral interactions or use as a disguise in these interactions. Here we review the experimental literature on machines as moral agents, moral patients, and moral proxies, with a focus on recent findings and the open questions that they suggest.
Satellite‐Synoptic Monitoring of Dominant Dust Entering Western Iran
Authors: Shahabi Himan , Safarrad Taher , Hashim Mazlan , Al-Ansari Nadhir
Published: September 2023

Dust storm in Iran’s western regions has been one of its major environmental problems in recent years, which has not only turned into a yearly phenomenon but is also expanding. This study investigated two events of dominant dust in southwestern Iran using moderate resolution imaging spectroradiometer imagery, Reanalysis Datasets (meteorological fields and atmospheric compositions), in both hot (July 2, 2008) and cold (February 18, 2017) seasons. After radiometric correction and calculation of brightness temperature as well as the reflective and thermal behavior of dust, the research results showed that the detection of dominant dust entering was 0.645 μm (visible red) and 0.858 μm (near‐infrared) in the reflective ranges and 3.959, 8.55, 11.03, and 12.02 µm in the thermal ranges. Synoptically, the lower values for mean sea level pressure from the east Mediterranean along Syria and Iraq to the southwest and Central Asia facilitate a convergence condition in the lower troposphere that induces strong northwesterlies, Shamal winds, over the Middle East toward the Persian Gulf, forming a more expansive aerosol hotspot over southwest Iran. However, on a cold day, high dust events in Arabia and south Iran are related to the ongoing high pressure, which is accompanied by a subtropical jet, following anticyclonic circulation toward southwestern Iran.