bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

ABSTRACT

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.
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

AbstractIn 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

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

ObjectivesThe study estimated the shortages of oncology medicines in Pakistan, their causes, impacts, mitigation strategies, and possible interventions.DesignCross-sectional survey.SettingOncology 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.ParticipantsOncology 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 measuresTo estimate the prevalence of oncology medicine shortages in Pakistan and establish recommendations to overcome them.ResultsOf 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.ConclusionPakistan’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

ObjectiveInvestigate 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.DesignLongitudinal 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.SettingFour adjacent municipalities in Central Norway.ParticipantsNon-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).MeasuresDependent 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.ResultsThe 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).ConclusionsThere 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

IntroductionThis 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 analysisThe 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 disseminationThis 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 numberThis 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

IntroductionCoronary 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 analysisThis 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 disseminationThis study is a systematic review of published literature data and no special ethical approval was required.PROSPERO registration numberCRD42022346189.
Early Diagnostic Value of KIM-1, NGAL, and NLR in Acute Kidney Injury Caused by Diquat Poisoning
Authors: Liu Tiezhen , Liu Qian , Qi Hongna , Xu Wenpin , Gao Xun , Wang Weizhan , Zhu Baoyue 
Published: September 2023

Background. The kidney is the main excretory organ after diquat absorption. Acute kidney injury (AKI) is a common complication in diquat poisoning patients. Objectives. To identify the value of combined detection of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and neutrophil-lymphocyte ratio (NLR) in the early diagnosis of diquat-induced AKI. Materials and Methods. The retrospective cohort study included 42 diquat poisoning patients. Results. Forty-two patients with diquat poisoning were included, of which 20 had fulminant poisoning (47.6%). At admission (0 h), levels of KIM-1, NGAL, NLR, and acute physiology and chronic health evaluation (APACHE) II scores in the fulminant poisoning group were higher than that of the moderate to severe poisoning group (

P

< 0.05), and they were all higher than in the control group (

P

< 0.05), while blood urea nitrogen (BUN) and uric acid (UA) levels did not significantly differ across the three groups (

P

> 0.05). At 12 h and 24 h, the levels of KIM-1, NGAL, NLR, UA, BUN, and APACHE II scores of patients in the fulminant poisoning group were higher than those in the moderate to severe poisoning group (

P

< 0.05), 12 h were higher than 0 h, and 24 h were higher than 12 h (

P

< 0.05). Among 42 patients with diquat poisoning, 28 had AKI (66.7%). At 0 h, the AKI group had higher levels of KIM-1, NGAL, NLR, and APACHE II scores than in the non-AKI (NAKI) group (

P

< 0.05), while there was no significant difference in BUN and UA levels between the two groups (

P

> 0.05). At 12 h and 24 h, the levels of KIM-1, NGAL, NLR, UA, BUN, and APACHE II scores in the AKI group were higher than those in the NAKI group (

P

< 0.05), 12 h were higher than 0 h, and 24 h were higher than 12 h (

P

< 0.05). KIM-1, NGAL, and NLR are independent risk markers for AKI in diquat poisoning patients. At admission (0 h), the combined application of KIM-1, NGAL, and NLR’s sensitivity, specificity, and area under the curve (AUC) for predicting AKI in diquat poisoning patients was 0.893, 0.859, and 0.903, respectively. Conclusions. KIM-1, NGAL, and NLR can be employed as early diagnostic indicators for the clinical prediction of AKI in diquat poisoning patients. Our findings may help clinicians reduce the occurrence of AKI.
RANK Expression as an Independent Predictor for Response to Neoadjuvant Chemotherapy in Luminal-Like Breast Cancer: A Translational Insight from the GeparX Trial
Authors: Link Theresa , Blohmer Jens-Uwe , Schmitt Wolfgang D. , Kuhlmann Jan Dominik , Just Marianne , Untch Michael , Stotzer Oliver , Fasching Peter A. , Thill Marc , Reinisch Mattea , Schneeweiss Andreas , Wimberger Pauline , Seiler Sabine , Huober Jens , Jackisch Christian , Rhiem Kerstin , Hanusch Claus , Sinn Bruno V. , Nekljudova Valentina , Loibl Sibylle , Denkert Carsten 
Published: September 2023

Abstract

Purpose:
The GeparX study investigated whether denosumab as add-on treatment to nab-paclitaxel–based neoadjuvant chemotherapy (NACT) with two different schedules (125 mg/m² weekly vs. day 1, 8 every 22 days) may increase pathologic complete response (pCR) rate. The addition of denosumab to NACT did not improve pCR rates as recently published. In this study, we investigated whether receptor activator of nuclear factor-kappa B (RANK) expression, as part of the denosumab target pathway: (i) may retrospectively identify a subgroup of patients with additional clinical benefit of denosumab or (ii) may predict response to nab-paclitaxel NACT.

Experimental Design:
RANK protein was IHC-stained on pre-therapeutic core biopsies from patients of the GeparX study (n = 667) with the antibody RANK/Envision System HRP (DAB) and was analyzed for the percentage of membranous RANK tumor cell staining (&gt;5% RANKhigh vs. ≤5% RANKlow).

Results:
We could not identify any patient subgroup with differential response under denosumab add-on treatment in patients with RANKhigh expression [139/667, 20.8%; OR, 0.86; 95% confidence interval (CI), 0.44–1.68; P = 0.667] or RANKlow expression (528/667 (79.2%) OR, 1.10; 95% CI, 0.78–1.56; P = 0.589; Pinteraction = 0.528). However, the pCR rate was higher in the RANKhigh subgroup compared with RANKlow (50% vs. 39%; OR, 1.52; 95% CI, 1.04–2.21; P = 0.037). RANK expression constituted an independent predictor of response to NACT frequently in patients with luminal-like subtype (HR+/HER2−; OR, 2.98; 95% CI, 1.30–6.79; P = 0.010). No predictive value of RANK expression among the different nab-paclitaxel regimens was observed.

Conclusion:
We report RANK expression to be an independent predictive biomarker for response to NACT in patients with luminal-like breast cancer.
Novel Clinical Trial Designs with Dose Optimization to Improve Long-term Outcomes
Authors: Thall Peter F. , Zang Yong , Chapple Andrew G. , Yuan Ying , Lin Ruitao , Marin David , Msaouel Pavlos 
Published: September 2023

AbstractConventional designs for choosing a dose for a new therapy may select doses that are unsafe or ineffective and fail to optimize progression-free survival time, overall survival time, or response/remission duration. We explain and illustrate limitations of conventional dose-finding designs and make four recommendations to address these problems. When feasible, a dose-finding design should account for long-term outcomes, include screening rules that drop unsafe or ineffective doses, enroll an adequate sample size, and randomize patients among doses. As illustrations, we review three designs that include one or more of these features. The first illustration is a trial that randomized patients among two cell therapy doses and standard of care in a setting where it was assumed on biological grounds that dose toxicity and dose–response curves did not necessarily increase with cell dose. The second design generalizes phase I–II by first identifying a set of candidate doses, rather than one dose, randomizing additional patients among the candidates, and selecting an optimal dose to maximize progression-free survival over a longer follow-up period. The third design combines a phase I–II trial and a group sequential randomized phase III trial by using survival time data available after the first stage of phase III to reoptimize the dose selected in phase I–II. By incorporating one or more of the recommended features, these designs improve the likelihood that a selected dose or schedule will be optimal, and thus will benefit future patients and obtain regulatory approval.