bluuebunny/crossref_metadata_2025_split huggingface dataset:
Care pathways of sepsis survivors: sequelae, mortality and use of healthcare services in France, 2015–2018
Authors: Pandolfi Fanny , Brun-Buisson Christian , Guillemot Didier , Watier Laurence 
Published: November 2023

Abstract
Background
Individuals who survive sepsis are at high risk of chronic sequelae, resulting in significant health-economic costs. Several studies have focused on aspects of healthcare pathways of sepsis survivors but comprehensive, longitudinal overview of their pathways of care are scarce. The aim of this retrospective, longitudinal cohort study is to identify sepsis survivor profiles based on their healthcare pathways and describe their healthcare consumption and costs over the 3 years following their index hospitalization.

Methods
The data were extracted from the French National Hospital Discharge Database. The study population included all patients above 15 years old, with bacterial sepsis, who survived an incident hospitalization in an acute care facility in 2015. To identify survivor profiles, state sequence and clustering analyses were conducted over the year following the index hospitalization. For each profile, patient characteristics and their index hospital stay and sequelae were described, as well as use of care and its associated monetary costs, both pre- and post-sepsis.

Results
New medical (79.2%), psychological (26.9%) and cognitive (18.5%) impairments were identified post-sepsis, and 65.3% of survivors were rehospitalized in acute care. Cumulative mortality reached 36.6% by 3 years post-sepsis. The total medical cost increased by 856 million € in the year post-sepsis. Five patient clusters were identified: home (65.6% of patients), early death (12.9%), late death (6.8%), short-term rehabilitation (11.3%) and long-term rehabilitation (3.3%). Survivors with early and late death clusters had high rates of cancer and primary bacteremia and experienced more hospital-at-home care post-sepsis. Survivors in short- or long-term rehabilitation clusters were older, with higher percentage of septic shock than those coming back home, and had high rates of multiple site infections and higher rates of new psychological and cognitive impairment.

Conclusions
Over three years post-sepsis, different profiles of sepsis survivors were identified with different mortality rates, sequels and healthcare services usage and cost. This study confirmed the importance of sepsis burden and suggests that strategies of post-discharge care, in accordance with patient profile, should be further tested in order to reduce sepsis burden.
AMEERA-4: a randomized, preoperative window-of-opportunity study of amcenestrant versus letrozole in early breast cancer
Authors: Campone Mario , Bidard François-Clément , Neven Patrick , Wang Lei , Ling Bin , Dong Yvonne , Paux Gautier , Herold Christina , De Giorgi Ugo 
Published: November 2023

Abstract
Background
Window-of-opportunity (WOO) studies provide insights into the clinical activity of new drugs in breast cancer.

Methods
AMEERA-4 (NCT04191382) was a WOO study undertaken to compare the pharmacodynamic effects of amcenestrant, a selective estrogen receptor degrader, with those of letrozole in postmenopausal women with newly diagnosed, operable estrogen receptor–positive, human epidermal growth factor receptor 2−negative (ER+/HER2−) breast cancer. Women were randomized (1:1:1) to receive amcenestrant 400 mg, amcenestrant 200 mg, or letrozole 2.5 mg once daily for 14 days before breast surgery. The primary endpoint was change in Ki67 between baseline and Day 15 (i.e., day of surgery).

Results
Enrollment was stopped early because of slow recruitment, in the context of the COVID-19 pandemic. The modified intent-to-treat population consisted of 95 study participants with baseline and post-treatment Ki67 values, whereas the safety population included 104 participants who had received at least one dose of study medication. Relative change from baseline in Ki67 was − 75.9% (95% confidence interval [CI] − 81.9 to − 67.9) for amcenestrant 400 mg, − 68.2% (− 75.7 to − 58.4) for amcenestrant 200 mg, and − 77.7% (− 83.4 to − 70.0) for letrozole (geometric least-squares mean [LSM] estimates). Absolute change in ER H-score from baseline (LSM estimate) was − 176.7 in the amcenestrant 400 mg arm, − 202.9 in the amcenestrant 200 mg arm, and − 32.5 in the letrozole arm. There were no Grade ≥ 3 treatment-related adverse events.

Conclusions
Both amcenestrant and letrozole demonstrated antiproliferative activity in postmenopausal women with previously untreated, operable ER+/HER2− breast cancer and had good overall tolerability.

Trial Registration

ClinicalTrials.gov, NCT04191382 https://clinicaltrials.gov/ct2/show/NCT04191382. Registered 9 December 2019.
Blocking channels to metastasis: targeting sodium transport in breast cancer
Authors: Brackenbury William J. , Palmieri Carlo 
Published: November 2023

AbstractThe development of therapies that can suppress invasion and prevent metastasis, ‘anti-metastatic drugs’, is an important area of unmet therapeutic need. The new results of a recent open-label, multicentre randomised trial published in J Clin Oncol showed a significant disease-free survival (DFS) benefit for breast cancer patients receiving presurgical, peritumoral injection of lidocaine, an amide local anaesthetic, which blocks voltage-gated sodium channels (VGSCs). VGSCs are expressed on electrically excitable cells, including neurons and cardiomyocytes, where they sustain rapid membrane depolarisation during action potential firing. As a result of this key biophysical function, VGSCs are important drug targets for excitability-related disorders, including epilepsy, neuropathic pain, affective disorders and cardiac arrhythmia. A growing body of preclinical evidence highlights VGSCs as key protagonists in regulating altered sodium influx in breast cancer cells, thus driving invasion and metastasis. Furthermore, prescription of certain VGSC-inhibiting medications has been associated with reduced cancer incidence and improved survival in several observational studies. Thus, VGSC-inhibiting drugs already in clinical use may be ideal candidates for repurposing as possible anti-metastatic therapies. While these results are promising, further work is required to establish whether other VGSC inhibitors may afford superior metastasis suppression. Finally, increasing preclinical evidence suggests that several other ion channels are also key drivers of cancer hallmarks; thus, there are undoubtedly further opportunities to harness ion transport inhibition that should also be explored.
Comparison of different weight-based scalars of remimazolam tosylate for anesthesia induction in obese patients: study protocol for a prospective, controlled trial
Authors: Ni Wenwen , Yi Xiuwen , Feng Lili , Shen Yilei , Jiao Jiali , Cai Yirong , Fu Danyun , Han Yuan , Jia Ji’e , Li Wenxian 
Published: November 2023

Abstract
Background
The physiologic and anthropometric characteristics changes associated with obesity may result in the alternation of pharmacologic management. Remimazolam tosylate is a new type of ultra-short-acting benzodiazepine with stable context-sensitive half-time (CSHT) and no lipid accumulation after long-time infusion. Although remimazolam tosylate has potential advantages for the induction and maintenance of anesthesia in obese patients, the appropriate induction dosing scalars among obese patients are unknown. Therefore, we aim to compare the different weight-based scalars for dosing remimazolam tosylate of anesthesia induction among obese patients.

Methods/design
The study will be performed as a prospective, single-center, double-blind, controlled clinical trial. The study design is a comparison of remimazolam tosylate requirements based on total body weight (TBW) or lean body weight (LBW) to reach a Modified Observer’s Assessment of Alertness and Sedation (MOAA/S) score of 0 among obese subjects (BMI ≥ 35 kg/m2). Another twenty normal-weight subjects (18.5 kg/m2 ≤ BMI < 25 kg/m2) will be enrolled as a control group, whose induction dose is scaled based on TBW. The infusion rate of remimazolam tosylate during induction is 12 mg/kg/h in all groups.

Discussion
Results of the present study will provide evidence of dose scalar of remimazolam tosylate to guide the clinical practice of anesthesia induction in obese patients.

Trial registration
Chinese Clinical Trial Registry ChiCTR220005664. Registered on 9 February 2022, https://www.chictr.org.cn/showproj.aspx?proj=151150.
Rapid profiling of Plasmodium parasites from genome sequences to assist malaria control
Authors: Phelan Jody E. , Turkiewicz Anna , Manko Emilia , Thorpe Joseph , Vanheer Leen N. , van de Vegte-Bolmer Marga , Ngoc Nguyen Thi Hong , Binh Nguyen Thi Huong , Thieu Nguyen Quang , Gitaka Jesse , Nolder Debbie , Beshir Khalid B. , Dombrowski Jamille G. , Di Santi Silvia Maria , Bousema Teun , Sutherland Colin J. , Campino Susana , Clark Taane G. 
Published: November 2023

Abstract
Background
Malaria continues to be a major threat to global public health. Whole genome sequencing (WGS) of the underlying Plasmodium parasites has provided insights into the genomic epidemiology of malaria. Genome sequencing is rapidly gaining traction as a diagnostic and surveillance tool for clinical settings, where the profiling of co-infections, identification of imported malaria parasites, and detection of drug resistance are crucial for infection control and disease elimination. To support this informatically, we have developed the Malaria-Profiler tool, which rapidly (within minutes) predicts Plasmodium species, geographical source, and resistance to antimalarial drugs directly from WGS data.

Results
The online and command line versions of Malaria-Profiler detect ~ 250 markers from genome sequences covering Plasmodium speciation, likely geographical source, and resistance to chloroquine, sulfadoxine-pyrimethamine (SP), and other anti-malarial drugs for P. falciparum, but also providing mutations for orthologous resistance genes in other species. The predictive performance of the mutation library was assessed using 9321 clinical isolates with WGS and geographical data, with most being single-species infections (P. falciparum 7152/7462, P. vivax 1502/1661, P. knowlesi 143/151, P. malariae 18/18, P. ovale ssp. 5/5), but co-infections were identified (456/9321; 4.8%). The accuracy of the predicted geographical profiles was high to both continental (96.1%) and regional levels (94.6%). For P. falciparum, markers were identified for resistance to chloroquine (49.2%; regional range: 24.5% to 100%), sulfadoxine (83.3%; 35.4– 90.5%), pyrimethamine (85.4%; 80.0–100%) and combined SP (77.4%). Markers associated with the partial resistance of artemisinin were found in WGS from isolates sourced from Southeast Asia (30.6%).

Conclusions
Malaria-Profiler is a user-friendly tool that can rapidly and accurately predict the geographical regional source and anti-malarial drug resistance profiles across large numbers of samples with WGS data. The software is flexible with modifiable bioinformatic pipelines. For example, it is possible to select the sequencing platform, display specific variants, and customise the format of outputs. With the increasing application of next-generation sequencing platforms on Plasmodium DNA, Malaria-Profiler has the potential to be integrated into point-of-care and surveillance settings, thereby assisting malaria control. Malaria-Profiler is available online (bioinformatics.lshtm.ac.uk/malaria-profiler) and as standalone software (https://github.com/jodyphelan/malaria-profiler).
Open innovation: the missing nexus between entrepreneurial orientation, total quality management, and performance of SMEs
Authors: Asad Muzaffar , Asif Muhammad Uzair , Sulaiman Mohammed Ali Bait Ali , Satar Mir Shahid , Alarifi Ghadah 
Published: November 2023

AbstractDrawing upon the theoretical foundations of the resource-based view, the current research aims to examine the mediating role of open innovation between entrepreneurial orientation, total quality management, and SMEs performance. Open innovation is not new, but SMEs operating in the developing economies are unaware of it importance and need. A structural equation model was used in the study to evaluate the relationships between the data collected from 270 SMEs with the help of adopted questionnaires. The results confirmed the impact of entrepreneurial along with total quality management on open innovation as well as the performance of SMEs. Second, the indirect impact of entrepreneurial orientation along with total quality management via open innovation has also been established which is proven as significant. Owners and managers of SMEs should consider customer-driven practices in an entrepreneurial manner to achieve elevated levels of performance based on the study’s findings.
Preoperative moderate to severe anemia is associated with increased postoperative major adverse cardiac and cerebral events and pulmonary complications: a propensity score-matched analysis in hip fracture surgery patients over 80 years old
Authors: Min Li , Linyi Yang , Chen Li , Jiang Shen , Chen Chen 
Published: November 2023

Abstract
Background
Anemia is a common health problem in the elderly. Preoperative anemia is a risk factor for postoperative outcomes in the elderly for hip fracture. The objective of the study was to explore the relationship between preoperative moderate to severe anemia and postoperative morbidity and mortality in hip fracture patients over 80 years old.

Methods
We performed a retrospective cohort study exploring preoperative moderate to severe anemia and postoperative morbidity and mortality. Patients over 80 years old undergoing hip fracture surgery were included in the study. Data were collected for major adverse cardiac and cerebral events (MACCE), postoperative pulmonary complications (PPCs), in-hospital mortality, delirium, gastrointestinal complication, deep venous thrombus (DVT), acute renal failure, ICU admission, and perioperative transfusion > 2 units rate.

Results
A total of 912 eligible patients were included for unmatched cohort analysis, and 512 patients were included for matched cohort analysis after propensity score matching. Baseline characteristics between the normal to mild anemia and moderate to severe anemia groups were significantly different. More patients in the moderate to severe cohort had a higher ASA classification grade III and female ratio. Patients in the moderate and severe anemia cohorts had more MACCE (unadjusted: odds ratio [OR] 1.968, 96% CI 1.090–3.555, P 0.023; adjusted: OR 1.929, 95% CI 1.014–3.668, P 0.045) and PPCs (unadjusted: OR 2.616, 95% CI 1.442–4.748, P 0.001; adjusted: OR 2.352, 95% CI 1.225–4.516, P 0.010) than patients with normal or mild anemia. However, the transfusion > 2 units rate was not significantly different between the two cohorts (unadjusted: OR 0.967, 95% CI 0.737–1.270, P 0.811; adjusted: OR 0.941, 95% CI 0.693–1.278, P 0.697). The in-hospital mortality, delirium rate, gastrointestinal complication, ICU admission, and DVT were similar. However, the in-hospital mortality was much higher (3.6%, 21/591 vs 1.6%, 5/321) in the moderate to severe anemia cohort. Furthermore, after propensity score-matched analysis, MACCE and PPCs were also significantly increased in the moderate to severe anemia cohort (OR 2.196 & 3.171, 95% CI 1.0794.470 & 1.563–6.436, P 0.027 & 0.001), which were in accordance with the unadjusted and adjusted results in the unmatched cohorts.

Conclusions
Moderate to severe preoperative anemia (< 11 g/dl) is associated with increased postoperative major adverse cardiac and cerebral events and pulmonary complications. Additionally, in-hospital mortality was not significant but was higher in the preoperative moderate to severe anemia cohort. Preoperative assessment and correction of hemoglobin level to above 11 g/dl might reduce MACCE, PPCs, and in-hospital mortality in hip fracture patients over 80 years old.
A novel transgenic mouse line with hippocampus-dominant and inducible expression of truncated human tau
Authors: Gao Yang , Wang Yuying , Lei Huiyang , Xu Zhendong , Li Shihong , Yu Haitao , Xie Jiazhao , Zhang Zhentao , Liu Gongping , Zhang Yao , Zheng Jie , Wang Jian-Zhi 
Published: November 2023

Abstract
Background
Intraneuronal accumulation of hyperphosphorylated tau is a defining hallmark of Alzheimer’s disease (AD). However, mouse models imitating AD-exclusive neuronal tau pathologies are lacking.

Methods
We generated a new tet-on transgenic mouse model expressing truncated human tau N1-368 (termed hTau368), a tau fragment increased in the brains of AD patients and aged mouse brains. Doxycycline (dox) was administered in drinking water to induce hTau368 expression. Immunostaining and Western blotting were performed to measure the tau level. RNA sequencing was performed to evaluate gene expression, and several behavioral tests were conducted to evaluate mouse cognitive functions, emotion and locomotion.

Results
Dox treatment for 1–2 months at a young age induced overt and reversible human tau accumulation in the brains of hTau368 transgenic mice, predominantly in the hippocampus. Meanwhile, the transgenic mice exhibited AD-like high level of tau phosphorylation, glial activation, loss of mature neurons, impaired hippocampal neurogenesis, synaptic degeneration and cognitive deficits.

Conclusions
This study developed a well-characterized and easy-to-use tool for the investigations and drug development for AD and other tauopathies.
A scoping review of emotion regulation and inhibition in emotional eating and binge-eating disorder: what about a continuum?
Authors: Arexis Mahé , Feron Gilles , Brindisi Marie-Claude , Billot Pierre-Édouard , Chambaron Stéphanie 
Published: November 2023

AbstractBackgroundEmotional eating is defined as a nonpathological eating behavior, whereas binge-eating disorder (BED) is defined as a pathological eating behavior. While different, both share some striking similarities, such as deficits in emotion regulation and inhibition. Previous research has suggested the existence of an “eating continuum” that might reflect the increased severity of overeating behaviors, that is, from nonpathological overeating to BED. The main aims of this scoping review were to explore in the literature the idea of a continuum between emotional eating and BED and to observe whether deficits in emotion regulation and inhibition follow this continuum in terms of severity. The other aims were to hopefully clarify the ill-defined concept of overeating, to question the potential role of positive emotions and to identify potential knowledge gaps.MethodA systematic scoping review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. Two databases (PubMed/Medline and PsycINFO) were examined in complete accordance with the beforehand sharply defined eligibility and exclusion criteria. The main criteria included adults (≥ 18) with emotional eating, BED or overeating and emotion regulation and inhibition as exposure criteria.ResultsThirty-two studies were included in this scoping review. If the results showed a link between emotional eating and BED, with the presence of inhibition and emotion regulation deficits in both eating behaviors, no mention of a continuum between emotional eating and BED was found.ConclusionIn the absence of research directly comparing emotional eating and BED in the same studies and testing the potential increase in severity of emotion regulation and inhibition deficits along this continuum, there is currently no certainty that a continuum exists between emotional eating and BED. In the end, the idea of a continuum in terms of increased severity of overeating and in terms of emotion regulation and inhibition deficits between emotional eating and BED appears to be a gap in knowledge in the literature. This scoping review highlights the need for further research to identify knowledge gaps.
Anticipatory and consummatory pleasure in avoidant/restrictive food intake disorder
Authors: Dolan Sarah C. , Kambanis P. Evelyna , Stern Casey M. , Becker Kendra R. , Breithaupt Lauren , Gydus Julia , Smith Sarah , Misra Madhusmita , Micali Nadia , Lawson Elizabeth A. , Eddy Kamryn T. , Thomas Jennifer J. 
Published: November 2023

Abstract
Background
Recent research suggests that individuals with eating disorders (EDs) report elevated anhedonia, or loss of pleasure. Although individuals with avoidant/restrictive food intake disorder (ARFID) often express that they do not look forward to eating, it is unclear whether they experience lower pleasure than those without EDs. Thus, identifying whether individuals with ARFID experience anhedonia may yield important insights that inform clinical conceptualization and treatment.

Methods
A sample of 71 participants ages 10–23 with full and subthreshold ARFID and 33 healthy controls (HCs) completed the Pica, ARFID, and Rumination Disorder Interview, a diagnostic interview to assess ARFID profile severity (lack of interest in food, sensory sensitivity, fear of aversive consequences) and the Temporal Experience of Pleasure Scale (TEPS), a self-report measure of consummatory and anticipatory pleasure. Statistical analyses were performed using the full TEPS and also the TEPS with food-related items removed.

Results
The ARFID group reported significantly lower anticipatory and consummatory pleasure compared to HCs, but these differences were no longer significant after controlling for depression, nor after removing food items from the TEPS. Within the ARFID sample, greater ARFID severity was associated with lower anticipatory pleasure across analyses, and greater endorsement of the lack of interest in food profile was related to lower anticipatory pleasure. ARFID severity was also associated with lower consummatory pleasure using the full TEPS, but this relationship was no longer significant with food items removed.

Conclusions
These results provide initial evidence for lower pleasure before potentially pleasurable events in individuals with more severe ARFID, particularly those with the lack of interest phenotype. Our findings also suggest that depression is likely to contribute low pleasure in this population. Future research should seek to further characterize how dimensions of pleasure relate to the maintenance and treatment of ARFID symptoms.