bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotypic and genotypic discrepancies for carbapenemase-producing Citrobacter freundii in multiple isolates from a single patient
Authors: Brecher Stephen M. , Tickler Isabella A. , Tenover Fred C. 
Published: April 2023

Abstract
Background
Carbapenemase-producing gram-negative organisms continue to be a significant healthcare concern and a therapeutic challenge. Members of the genus Citrobacter have emerged as increasingly multidrug resistant and versatile healthcare-associated pathogens. In this study we investigated five KPC-producing Citrobacter freundii isolates, from the same patient, that presented unusual phenotypic characteristics including false susceptibility to carbapenems detection by culture-based methods.

Methods
The isolates were tested for antimicrobial susceptibility using broth microdilution and disk diffusion. Production of serine carbapenemase was confirmed with the mCIM (modified carbapenem inactivation method) test. Genotypes were determined by PCR and whole genome sequencing analysis.

Results
The five isolates were susceptible to meropenem by broth microdilution and presented varying colonial morphologies and levels of susceptibility to carbapenems by multiple phenotypic methods, despite being positive for carbapenemase production by mCIM and positive for blaKPC by PCR. Whole genome sequence analysis showed that three of the five highly related isolates harbor an additional gene cassette, including blaCARB-2, ant(2''), aadA2, dfrA19, catB3, cmlA1, mph(E), msr(E), and qnrA1. The presence of these genes explains the difference in phenotypes observed.

Conclusion
Failure to detect and completely eradicate the carbapenemase-producing C. freundii in the urine with ertapenem therapy, likely due to the presence of a heterogeneous population, resulted in the phenotypic and genotypic adaptations of the organism as it disseminated to the bloodstream and kidneys. The fact that carbapenemase-producing C. freundii can elude detection by phenotypic methods and can so easily acquire and transfer resistance gene cassettes is of concern.
Immunotherapy of thymic epithelial tumors: molecular understandings and clinical perspectives
Authors: Ao Yong-Qiang , Gao Jian , Wang Shuai , Jiang Jia-Hao , Deng Jie , Wang Hai-Kun , Xu Bei , Ding Jian-Yong 
Published: April 2023

AbstractImmunotherapy has emerged to play a rapidly expanding role in the treatment of cancers. Currently, many clinical trials of therapeutic agents are on ongoing with majority of immune checkpoint inhibitors (ICIs) especially programmed death receptor 1 (PD-1) and its ligand 1 (PD-L1) inhibitors. PD-1 and PD-L1, two main immune checkpoints, are expressed at high levels in thymic epithelial tumors (TETs) and could be predictors of the progression and immunotherapeutic efficacy of TETs. However, despite inspiring efficacy reported in clinical trials and clinical practice, significantly higher incidence of immune-related adverse events (irAEs) than other tumors bring challenges to the administration of ICIs in TETs. To develop safe and effective immunotherapeutic patterns in TETs, understanding the clinical properties of patients, the cellular and molecular mechanisms of immunotherapy and irAEs occurrence are crucial. In this review, the progress of both basic and clinical research on immune checkpoints in TETs, the evidence of therapeutic efficacy and irAEs based on PD-1 /PD-L1 inhibitors in TETs treatment are discussed. Additionally, we highlighted the possible mechanisms underlying irAEs, prevention and management strategies, the insufficiency of current research and some worthy research insights. High PD-1/PD-L1 expression in TETs provides a rationale for ICI use. Completed clinical trials have shown an encouraging efficacy of ICIs, despite the high rate of irAEs. A deeper mechanism understanding at molecular level how ICIs function in TETs and why irAEs occur will help maximize the immunotherapeutic efficacy while minimizing irAEs risks in TET treatment to improve patient prognosis.
Surgical outcomes of left hemicolon sparing resection versus extensive resection in treating synchronous colorectal cancer involving the right-sided colon and sigmoid colon or rectum
Authors: Quan Jichuan , Liu Junguang , Zhou Sicheng , Mei Shiwen , Qiu Wenlong , Wan Yuanlian , Wang Xishan , Tang Jianqiang 
Published: April 2023

Abstract
Background
There are different surgical strategies that can treat synchronous colorectal cancer (SCRC) involving separate segments, namely extensive resection (EXT) and left hemicolon-sparing resection (LHS). We aim to comparatively analyze short-term surgical results, bowel function, and long-term oncological outcomes between SCRC patients treated with the two different surgical strategies.

Methods
One hundred thirty-eight patients with SCRC lesions located in the right hemicolon and rectum or sigmoid colon were collected at the Cancer Hospital, Chinese Academy of Medical Sciences, and the Peking University First Hospital from January 2010 to August 2021 and divided into EXT group (n = 35) and LHS group (n = 103), depending on their surgical strategies. These two groups of patients were compared for postoperative complications, bowel function, the incidence of metachronous cancers, and prognosis.

Results
The operative time for the LHS group was markedly shorter compared with the EXT group (268.6 vs. 316.9 min, P = 0.015). The post-surgery incidences of total Clavien-Dindo grade ≥ II complications and anastomotic leakage (AL) were 8.7 vs. 11.4% (P = 0.892) and 4.9 vs. 5.7% (P = 1.000) for the LHS and EXT groups, respectively. The mean number of daily bowel movements was significantly lower for the LHS group than for the EXT group (1.3 vs. 3.8, P < 0.001). The proportions of no low anterior resection syndrome (LARS), minor LARS, and major LARS for the LHS and EXT groups were 86.5 vs. 80.0%, 9.6 vs. 0%, and 3.8 vs. 20.0%, respectively (P = 0.037). No metachronous cancer was found in the residual left colon during the 51-month (median duration) follow-up period. The overall and disease-free survival rates at 5 years were 78.8% and 77.5% for the LHS group and 81.7% and 78.6% for the EXT group (P = 0.565, P = 0.712), respectively. Multivariate analysis further confirmed N stage, but not surgical strategy, as the risk factor that independently affected the patients’ survival.

Conclusions
LHS appears to be a more appropriate surgical strategy for SCRC involving separate segments because it exhibited shorter operative time, no increase in the risk of AL and metachronous cancer, and no adverse long-term survival outcomes. More importantly, it could better retain bowel function and tended to reduce the severity of LARS and therefore improve the post-surgery life quality of SCRC patients.
VSSP-activated macrophages mediate senescence and tumor inhibition in a preclinical model of advanced prostate cancer
Authors: Alvarez-Arzola Rydell , Bancaro Nicoló , Lai Ping , Attanasio Giuseppe , Pellegrini Laura , Troiani Martina , Colucci Manuel , Mosole Simone , Pasquini Emiliano , Alimonti Andrea , Mesa Circe 
Published: April 2023

AbstractAndrogen deprivation therapy (ADT) is a standard therapy for prostate cancer (PCa). Though disseminated disease is initially sensitive to ADT, an important fraction of the patients progresses to castration-resistant prostate cancer (CRPC). For this reason, the identification of novel effective therapies for treating CRPC is needed. Immunotherapeutic strategies focused on macrophages as antitumor effectors, directly enhancing their tumoricidal potential at the tumor microenvironment or their adoptive transfer after ex vivo activation, have arisen as promising therapies in several cancer types. Despite several approaches centered on the activation of tumor-associated macrophages (TAMs) in PCa are under investigation, to date there is no evidence of clinical benefit in patients. In addition, the evidence of the effectiveness of macrophage adoptive transfer on PCa is poor. Here we find that VSSP, an immunomodulator of the myeloid system, decreases TAMs and inhibits prostatic tumor growth when administered to castrated Pten-deficient prostate tumor-bearing mice. In mice bearing castration-resistant Ptenpc−/−; Trp53pc−/− tumors, VSSP administration showed no effect. Nevertheless, adoptive transfer of macrophages activated ex vivo with VSSP inhibited Ptenpc−/−; Trp53pc−/− tumor growth through reduction of angiogenesis and tumor cell proliferation and induction of senescence. Taken together, our results highlight the rationale of exploiting macrophage functional programming as a promising strategy for CRPC therapy, with particular emphasis on ex vivo-activated proinflammatory macrophage adoptive transfer.
Graphical abstract
A review of the regulatory mechanisms of extracellular vesicles-mediated intercellular communication
Authors: Liu Ya-Juan , Wang Cheng 
Published: April 2023

AbstractExtracellular vesicles (EVs) are small, membrane-bound structures that are released from cells into the surrounding environment. These structures can be categorized as exosomes, microvesicles, or apoptotic vesicles, and they play an essential role in intercellular communication. These vesicles are attracting significant clinical interest as they offer the potential for drug delivery, disease diagnosis, and therapeutic intervention. To fully understand the regulation of intercellular communication through EVs, it is essential to investigate the underlying mechanisms. This review aims to provide a summary of the current knowledge on the intercellular communications involved in EV targeting, binding, and uptake, as well as the factors that influence these interactions. These factors include the properties of the EVs, the cellular environment, and the recipient cell. As the field of EV-related intercellular communication continues to expand and techniques improve, we can expect to uncover more information about this complex area, despite the current limitations in our knowledge.
Characterization of prosthetic knees through a low-dimensional description of gait kinematics
Authors: Ranaldi Simone , De Marchis Cristiano , Serrao Mariano , Ranavolo Alberto , Draicchio Francesco , Lacquaniti Francesco , Conforto Silvia 
Published: April 2023

AbstractThe characterization of both limbs’ behaviour in prosthetic gait is of key importance for improving the prosthetic components and increasing the biomechanical capability of trans-femoral amputees. When characterizing human gait, modular motor control theories have been proven to be powerful in providing a compact description of the gait patterns. In this paper, the planar covariation law of lower limb elevation angles is proposed as a compact, modular description of prosthetic gait; this model is exploited for a comparison between trans-femoral amputees walking with different prosthetic knees and control subjects walking at different speeds. Results show how the planar covariation law is maintained in prostheses users, with a similar spatial organization and few temporal differences. Most of the differences among the different prosthetic knees are found in the kinematic coordination patterns of the sound side. Moreover, different geometrical parameters have been calculated over the common projected plane, and their correlation with classical gait spatiotemporal and stability parameters has been investigated. The results from this latter analysis have highlighted a correlation with several parameters of gait, suggesting that this compact description of kinematics unravels a significant biomechanical meaning. These results can be exploited to guide the control mechanisms of prosthetic devices based purely on the measurement of relevant kinematic quantities.
Thromboelastometry-guided haemostatic resuscitation in severely injured patients: a propensity score-matched study
Authors: David Jean-Stéphane , James Arthur , Orion Maxime , Selves Agathe , Bonnet Mélody , Glasman Pauline , Vacheron Charles-Hervé , Raux Mathieu 
Published: April 2023

Abstract
Background
To accelerate the diagnosis and treatment of trauma-induced coagulopathy (TIC), viscoelastic haemostatic assays (VHA) are increasingly used worldwide, although their value is still debated, with a recent randomised trial showing no improvement in outcome. The objective of this retrospective study was to compare 2 cohorts of injured patients in which TIC was managed with either a VHA-based algorithm or a conventional coagulation test (CCT)-based algorithm.

Methods
Data were retrieved from 2 registries and patients were included in the study if they received at least 1 unit of red blood cell in the first 24 h after admission. A propensity score, including sex, age, blunt vs. penetrating, systolic blood pressure, GCS, ISS and head AIS, admission lactate and PTratio, tranexamic acid administration, was then constructed. Primary outcome was the proportion of subjects who were alive and free of massive transfusion (MT) at 24 h after injury. We also compared the cost for blood products and coagulation factors.

Results
From 2012 to 2019, 7250 patients were admitted in the 2 trauma centres, and among these 624 were included in the study (CCT group: 380; VHA group: 244). After propensity score matching, 215 patients remained in each study group without any significant difference in demographics, vital signs, injury severity, or laboratory analysis. At 24 h, more patients were alive and free of MT in the VHA group (162 patients, 75%) as compared to the CCT group (112 patients, 52%; p < 0.01) and fewer patients received MT (32 patients, 15% vs. 91 patients, 42%, p < 0.01). However, no significant difference was observed for mortality at 24 h (odds ratio 0.94, 95% CI 0.59–1.51) or survival at day 28 (odds ratio 0.87, 95% CI 0.58–1.29). Overall cost of blood products and coagulation factors was dramatically reduced in the VHA group as compared to the CCT group (median [interquartile range]: 2357 euros [1108–5020] vs. 4092 euros [2510–5916], p < 0.001).

Conclusions
A VHA-based strategy was associated with an increase of the number of patients alive and free of MT at 24 h together with an important reduction of blood product use and associated costs. However, that did not translate into an improvement in mortality.
Association of lung recruitment and change in recruitment-to-inflation ratio from supine to prone position in acute respiratory distress syndrome
Authors: Del Sorbo Lorenzo , Tisminetzky Manuel , Chen Lu , Brochard Laurent , Arellano Daniel , Brito Roberto , Diaz Juan C. , Cornejo Rodrigo 
Published: April 2023

AbstractProne positioning is an evidence-based treatment for patients with moderate-to-severe acute respiratory distress syndrome. Lung recruitment has been proposed as one of the mechanisms by which prone positioning reduces mortality in this group of patients. Recruitment-to-inflation ratio (R/I) is a method to measure potential for lung recruitment induced by a change in positive end-expiratory pressure (PEEP) on the ventilator. The association between R/I and potential for lung recruitment in supine and prone position has not been studied with computed tomography (CT) scan imaging. In this secondary analysis, we sought to investigate the correlation between R/I measured in supine and prone position with CT and the potential for lung recruitment as measured by CT scan. Among 23 patients, the median R/I did not significantly change from supine (1.9 IQR 1.6–2.6) to prone position (1.7 IQR 1.3–2.8) (paired t test p = 0.051) but the individual changes correlated with the different response to PEEP. In supine and in prone position, R/I significantly correlated with the proportion of lung tissue recruitment induced by the change of PEEP. Lung tissue recruitment induced by a change of PEEP from 5 to 15 cmH2O was 16% (IQR 11–24%) in supine and 14.3% (IQR 8.4–22.6%) in prone position, as measured by CT scan analysis (paired t test p = 0.56). In this analysis, PEEP-induced recruitability as measured by R/I correlated with PEEP-induced lung recruitment as measured by CT scan, and could help to readjust PEEP in prone position.
Stalled oligodendrocyte differentiation in IDH-mutant gliomas
Authors: Wei Yanfei , Li Guanzhang , Feng Jing , Wu Fan , Zhao Zheng , Bao Zhaoshi , Zhang Wei , Su Xiaodong , Li Jiuyi , Qi Xueling , Duan Zejun , Zhang Yunqiu , Vega Sandra Ferreyra , Jakola Asgeir Store , Sun Yingyu , Carén Helena , Jiang Tao , Fan Xiaolong 
Published: April 2023

AbstractBackgroundRoughly 50% of adult gliomas harborisocitrate dehydrogenase(IDH) mutations. According to the 2021 WHO classification guideline, these gliomas are diagnosed as astrocytomas, harboring no 1p19q co-deletion, or oligodendrogliomas, harboring 1p19q co-deletion. Recent studies report that IDH-mutant gliomas share a common developmental hierarchy. However, the neural lineages and differentiation stages in IDH-mutant gliomas remain inadequately characterized.MethodsUsing bulk transcriptomes and single-cell transcriptomes, we identified genes enriched in IDH-mutant gliomas with or without 1p19q co-deletion, we also assessed the expression pattern of stage-specific signatures and key regulators of oligodendrocyte lineage differentiation. We compared the expression of oligodendrocyte lineage stage-specific markers between quiescent and proliferating malignant single cells. The gene expression profiles were validated using RNAscope analysis and myelin staining and were further substantiated using data of DNA methylation and single-cell ATAC-seq. As a control, we assessed the expression pattern of astrocyte lineage markers.ResultsGenes concordantly enriched in both subtypes of IDH-mutant gliomas are upregulated in oligodendrocyte progenitor cells (OPC). Signatures of early stages of oligodendrocyte lineage and key regulators of OPC specification and maintenance are enriched in all IDH-mutant gliomas. In contrast, signature of myelin-forming oligodendrocytes, myelination regulators, and myelin components are significantly down-regulated or absent in IDH-mutant gliomas. Further, single-cell transcriptomes of IDH-mutant gliomas are similar to OPC and differentiation-committed oligodendrocyte progenitors, but not to myelinating oligodendrocyte. Most IDH-mutant glioma cells are quiescent; quiescent cells and proliferating cells resemble the same differentiation stage of oligodendrocyte lineage. Mirroring the gene expression profiles along the oligodendrocyte lineage, analyses of DNA methylation and single-cell ATAC-seq data demonstrate that genes of myelination regulators and myelin components are hypermethylated and show inaccessible chromatin status, whereas regulators of OPC specification and maintenance are hypomethylated and show open chromatin status. Markers of astrocyte precursors are not enriched in IDH-mutant gliomas.ConclusionsOur studies show that despite differences in clinical manifestation and genomic alterations, all IDH-mutant gliomas resemble early stages of oligodendrocyte lineage and are stalled in oligodendrocyte differentiation due to blocked myelination program. These findings provide a framework to accommodate biological features and therapy development for IDH-mutant gliomas.
Compensatory muscle activation and spinal curve changes in response to fatigue among adolescent male athletes
Authors: Gál-Pottyondy Anna , Petró Bálint , Takács Mária , Négyesi János , Nagatomi Ryoichi , Kiss Rita M 
Published: April 2023

Abstract
Background
The prone plank test has been often used to assess the strength and endurance of trunk muscles. We aimed to develop a new measurement protocol to objectively monitor the changes in spinal curves and muscle activity simultaneously.

Methods
Eleven adolescent male basketball athletes (13–17 years) performed a one-minute plank test. Spinal curvatures (thoracic kyphosis (TK) and lumbar lordosis (LL)) were determined at each time point by optical tracking of markers placed on the spinous processes of 10 vertebrae. Eleven muscles were measured by surface electromyography to determine muscle fatigue via changes in median frequency.

Results
TK significantly increased (p = 0.003) from the first to the last 10 s of the plank test; changes in LL were mixed within the group. Only the rectus abdominis showed consistent and significant fatigue (p < 0.001). The increased spinal curves significantly correlated with the fatigue of biceps femoris (TK: r = -0.75, p = 0.012; LL: r = -0.71, p = 0.019) indicating a compensatory muscle activation and spinal curve changes in response to fatigue.

Conclusion
Our protocol may support future researches that aim to objectively evaluate the prone plank test and which posture-related muscles need strengthening for the individual.
Measuring appropriateness of diagnostic imaging: a scoping review
Authors: Walther Felix , Eberlein-Gonska Maria , Hoffmann Ralf-Thorsten , Schmitt Jochen , Blum Sophia F. U. 
Published: April 2023

AbstractIn radiology, the justification of diagnostic imaging is a key performance indicator. To date, specific recommendations on the measurement of appropriateness in diagnostic imaging are missing. To map the study literature concerning the definition, measures, methods and data used for analyses of appropriateness in research of diagnostic imaging. We conducted a scoping review in Medline, EMBASE, Scopus and the Cochrane Central Register of Controlled Trials. Two independent reviewers undertook screening and data extraction. After screening 6021 records, we included 50 studies. National guidelines (n = 22/50) or American College of Radiology Appropriateness Criteria (n = 23/50) were used to define and rate appropriateness. 22/50 studies did not provide methodological details about the appropriateness assessment. The included studies varied concerning modality, amount of reviewed examinations (88–13,941) and body regions. Computed tomography (27 studies, 27,168 examinations) was the most frequently analyzed modality, followed by magnetic resonance imaging (17 studies, 6559 examinations) and radiography (10 studies, 7095 examinations). Heterogeneous appropriateness rates throughout single studies (0–100%), modalities, and body regions (17–95%) were found. Research on pediatric and outpatient imaging was sparse. Multicentric, methodologically robust and indication-oriented studies would strengthen appropriateness research in diagnostic imaging and help to develop reliable key performance indicators.
Efficacy of exposure and response prevention therapy in mixed reality for patients with obsessive-compulsive disorder: study protocol for a randomized controlled trial
Authors: Lohse Luzie , Jelinek Lena , Moritz Steffen , Blömer Jannik , Bücker Lara , Miegel Franziska 
Published: April 2023

AbstractMany patients with obsessive-compulsive disorder (OCD) do not receive cognitive behavioral therapy with exposure and response prevention (first line treatment for OCD), for example, due to patients’ fear of the exposure and reservations of the therapists. Technology-supported exposure (e.g., exposure therapy with response prevention in mixed reality [MERP]) for patients with OCD may help to overcome this obstacle. Building upon findings of our pilot study objectives of this study are to evaluate the efficacy, expectations of treatment success, feasibility, and acceptance of MERP as well as to identify possible limitations. In total, 64 outpatients with contamination-related OCD will be recruited and randomized to one of two conditions: MERP (six sessions in six weeks) and self-guided exposure therapy (six exercises in six weeks). Participants will be assessed before (baseline), after the six-week intervention period (post), as well as three months after post assessment (follow-up) regarding symptomatology (Yale-Brown Obsessive Compulsive Scale; Y-BOCS), their subjective evaluation of MERP (acceptance) and sense of presence. The planned study is the first to investigate MERP in patients with OCD.