bluuebunny/crossref_metadata_2025 huggingface dataset:
The prescription drug monitoring program in a multifactorial approach to the opioid crisis: PDMP data, Pennsylvania, 2016–2020
Authors: Adalbert Jenna R. , Syal Amit , Varshney Karan , George Brandon , Hom Jeffrey , Ilyas Asif M.
Published: April 2023

Background

Prescription opioids remain an important contributor to the United States opioid crisis and to the development of opioid use disorder for opioid-naïve individuals. Recent legislative actions, such as the implementation of state prescription drug monitoring programs (PDMPs), aim to reduce opioid morbidity and mortality through enhanced tracking and reporting of prescription data. The primary objective of our study was to describe the opioid prescribing trends in the state of Pennsylvania (PA) as recorded by the PA PDMP following legislative changes in reporting guidelines, and discuss the PDMP’s role in a multifactorial approach to opioid harm reduction.

Methods

State-level opioid prescription data summaries recorded by the PA PDMP for each calendar quarter from August 2016 through March 2020 were collected from the PA Department of Health. Data for oxycodone, hydrocodone, and morphine were analyzed by quarter for total prescription numbers and refills. Prescription lengths, pill quantities, and average morphine milliequivalents (MMEs) were analyzed by quarter for all 14 opioid prescription variants recorded by the PA PDMP. Linear regression was conducted for each group of variables to identify significant differences in prescribing trends.

Results

For total prescriptions dispensed, the number of oxycodone, hydrocodone, and morphine prescriptions decreased by 34.4, 44.6, and 22.3% respectively (p < 0.0001). Refills fluctuated less consistently with general peaks in Q3 of 2017 and Q3 of 2018 (p = 0.2878). The rate of prescribing for all opioid prescription lengths decreased, ranging in frequency from 22 to 30 days (47.5% of prescriptions) to 31+ days of opioids (0.8% of prescriptions) (p < 0.0001). Similarly, decreased prescribing was observed for all prescription amounts, ranging in frequency from 22 to 60 pills (36.6% of prescriptions) to 60–90 pills (14.2% of prescriptions) (p < 0.0001). Overall, the average MME per opioid prescription decreased by 18.9%.

Conclusions

Per the PA PDMP database, opioid prescribing has decreased significantly in PA from 2016 to 2020. The PDMP database is an important tool for tracking opioid prescribing trends in PA, and PDMPs structured similarly in other states may enhance our ability to understand and influence the trajectory of the U.S. opioid crisis. Further research is needed to determine optimal PDMP policies and practices nationwide.
The effect of the hospital working environment on the work limitation of the employees in Turkey: a multivariable analysis
Authors: Kiliç Mahmut , Uslukiliç Güllü , Yaman Sevda
Published: April 2023

Background

The aim of this study is to examine the effects of working environment and demographic variables on the level of work limitation in a university hospital.

Methods

The study is cross-sectional and was conducted in 2022 among employees of a university hospital. 254 people voluntarily participated in the study. Data were collected by applying the sociodemographic data form, the Work Limitation Questionnaire (WLQ), and the Work Environment Scale (WES). Institutional permission and ethical approval were obtained for the study. In the analysis of the data, t-test, ANOVA, and linear regression (LR) were used.

Results

The WLQ score average of hospital staff was low. According to LR analysis, the factors affecting the level of work limitation of hospital staff; worsening perception of health status, being a doctor, decreased income level, increased working time in the institution, and age reduction. It was determined that 32.8% of the change in the WLQ score was related to these factors. While in the univariate tests, the mean of work limitation was found to be significant by getting occupational health safety training, having health problems due to the work done, and taking leave due to work accidents, in the multivariable LR analysis, these factors were insignificant.

Conclusions

As the working environment gets worse, the level of work limitation increases. It is recommended that hospital managers make the working environment better and safer, and make arrangements and programs to increase personnel satisfaction.
Promoter evolution of mammalian gene duplicates
Authors: Fraimovitch Evgeny , Hagai Tzachi
Published: April 2023

Background

Gene duplication is thought to be a central process in evolution to gain new functions. The factors that dictate gene retention following duplication as well paralog gene divergence in sequence, expression and function have been extensively studied. However, relatively little is known about the evolution of promoter regions of gene duplicates and how they influence gene duplicate divergence. Here, we focus on promoters of paralog genes, comparing their similarity in sequence, in the sets of transcription factors (TFs) that bind them, and in their overall promoter architecture.

Results

We observe that promoters of recent duplications display higher sequence similarity between them and that sequence similarity rapidly declines between promoters of more ancient paralogs. In contrast, similarity in cis-regulation, as measured by the set of TFs that bind promoters of both paralogs, does not simply decrease with time from duplication and is instead related to promoter architecture—paralogs with CpG Islands (CGIs) in their promoters share a greater fraction of TFs, while CGI-less paralogs are more divergent in their TF binding set.

Focusing on recent duplication events and partitioning them by their duplication mechanism enables us to uncover promoter properties associated with gene retention, as well as to characterize the evolution of promoters of newly born genes: In recent retrotransposition-mediated duplications, we observe asymmetry in cis-regulation of paralog pairs: Retrocopy genes are lowly expressed and their promoters are bound by fewer TFs and are depleted of CGIs, in comparison with the original gene copy. Furthermore, looking at recent segmental duplication regions in primates enable us to compare successful retentions versus loss of duplicates, showing that duplicate retention is associated with fewer TFs and with CGI-less promoter architecture.

Conclusions

In this work, we profiled promoters of gene duplicates and their inter-paralog divergence. We also studied how their characteristics are associated with duplication time and duplication mechanism, as well as with the fate of these duplicates. These results underline the importance of cis-regulatory mechanisms in shaping the evolution of new genes and their fate following duplication.
A tumor microenvironment-based prognostic index for osteosarcoma
Authors: Wu Changwu , Gong Siming , Duan Yingjuan , Deng Chao , Kallendrusch Sonja , Berninghausen Laura , Osterhoff Georg , Schopow Nikolas
Published: April 2023

Background

The tumor microenvironment (TME) has a central role in the oncogenesis of osteosarcomas. The composition of the TME is essential for the interaction between tumor and immune cells. The aim of this study was to establish a prognostic index (TMEindex) for osteosarcoma based on the TME, from which estimates about patient survival and individual response to immune checkpoint inhibitor (ICI) therapy can be deduced.

Methods

Based on osteosarcoma samples from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database, the ESTIMATE algorithm was used to estimate ImmuneScore and StromalScore. Combined differentially expressed gene analysis, weighted gene co-expression network analyses, the Least Absolute Shrinkage and Selection Operator regression and stepwise regression to construct the TMEindex. The prognostic role of TMEindex was validated in three independent datasets. The molecular and immune characteristics of TMEindex and the impact on immunotherapy were then comprehensively investigated. The expression of TMEindex genes in different cell types and its effects on osteosarcoma cells were explored by scRNA-Seq analysis and molecular biology experiments.

Results

Fundamental is the expression of MYC, P4HA1, RAMP1 and TAC4. Patients with high TMEindex had worse overall survival, recurrence-free survival, and metastasis-free survival. TMEindex is an independent prognostic factor in osteosarcoma. TMEindex genes were mainly expressed in malignant cells. The knockdown of MYC and P4HA1 significantly inhibited the proliferation, invasion and migration of osteosarcoma cells. A high TME index is related to the MYC, mTOR, and DNA replication-related pathways. In contrast, a low TME index is related to immune-related signaling pathways such as the inflammatory response. The TMEindex was negatively correlated with ImmuneScore, StromalScore, immune cell infiltration, and various immune-related signature scores. Patients with a higher TMEindex had an immune-cold TME and higher invasiveness. Patients with a low TME index were more likely to respond to ICI therapy and achieve clinical benefit. In addition, the TME index correlated with response to 29 oncologic drugs.

Conclusions

The TMEindex is a promising biomarker to predict the prognosis of patients with osteosarcoma and their response to ICI therapy, and to distinguish the molecular and immune characteristics.
The NF-ĸB p50 subunit generated by KPC1-mediated ubiquitination and limited proteasomal processing, suppresses tumor growth
Authors: Kravtsova-Ivantsiv Yelena , Goldhirsh Gilad , Tomuleasa Ciprian , Pikarsky Eli , Ciechanover Aaron
Published: April 2023

Nuclear factor-ĸB (NF-ĸB) is an important transcriptional regulator of key cellular processes, including cell cycle, immune response, and malignant transformation. We found that the ubiquitin ligase Kip1 ubiquitination-promoting complex subunit 1 (KPC1; also known as Ring finger protein 123 – RNF123) stimulates ubiquitination and limited proteasomal processing of the p105 NF-ĸB precursor to generate p50, the active subunit of the heterodimeric transcription factor. KPC1 binds to the ankyrin repeats’ (AR) domain of NF-ĸB p105 via a short binding site of 7 amino acids—968-WILVRLW-974. Though mature NF-ĸB is overexpressed and constitutively active in different tumors, we found that overexpression of the p50 subunit, exerts a strong tumor suppressive effect. Furthermore, excess of KPC1 that stimulates generation of p50 from the p105 precursor, also results in a similar effect. Analysis of transcripts of glioblastoma and breast tumors revealed that excess of p50 stimulates expression of many NF-ĸB-regulated tumor suppressive genes. Using human xenograft tumor models in different immune compromised mice, we demonstrated that the immune system plays a significant role in the tumor suppressive activity of p50:p50 homodimer stimulating the expression of the pro-inflammatory cytokines CCL3, CCL4, and CCL5 in both cultured cells and in the xenografts. Expression of these cytokines leads to recruitment of macrophages and NK cells, which restrict tumor growth. Finally, p50 inhibits the expression of the programmed cell death-ligand 1 (PDL1), establishing an additional level of a strong tumor suppressive response mediated by the immune system.
Monitoring variability in parameter estimates for lumped parameter models of the systemic circulation using longitudinal hemodynamic measurements
Authors: Bjørdalsbakke Nikolai L. , Sturdy Jacob , Ingeström Emma M. L. , Hellevik Leif R.
Published: April 2023

Background

Physics-based cardiovascular models are only recently being considered for disease diagnosis or prognosis in clinical settings. These models depend on parameters representing the physical and physiological properties of the modeled system. Personalizing these parameters may give insight into the specific state of the individual and etiology of disease. We applied a relatively fast model optimization scheme based on common local optimization methods to two model formulations of the left ventricle and systemic circulation. One closed-loop model and one open-loop model were applied. Intermittently collected hemodynamic data from an exercise motivation study were used to personalize these models for data from 25 participants. The hemodynamic data were collected for each participant at the start, middle and end of the trial. We constructed two data sets for the participants, both consisting of systolic and diastolic brachial pressure, stroke volume, and left-ventricular outflow tract velocity traces paired with either the finger arterial pressure waveform or the carotid pressure waveform.

Results

We examined the feasibility of separating parameter estimates for the individual from population estimates by assessing the variability of estimates using the interquartile range. We found that the estimated parameter values were similar for the two model formulations, but that the systemic arterial compliance was significantly different ($$p < 10^{-6}$$

p
<

10

-
6

) depending on choice of pressure waveform. The estimates of systemic arterial compliance were on average higher when using the finger artery pressure waveform as compared to the carotid waveform.

Conclusions

We found that for the majority of participants, the variability of parameter estimates for a given participant on any measurement day was lower than the variability both across all measurement days combined for one participant, and for the population. This indicates that it is possible to identify individuals from the population, and that we can distinguish different measurement days for the individual participant by parameter values using the presented optimization method.
A study on the current state and equity level of the health promotion service demands among older adults in China
Authors: Ren Weicun , Ma Xiwang , Tarimo Clifford Silver , Xing Yiqing , Lv Xinyuan , Liang Zhang
Published: April 2023

Background

Meeting the demands of older adults for health promotion services (DOAHPS) is essential for maintaining their health and enhancing their quality of life. The purpose of this study was to construct a model for evaluating DOAHPS to quantitatively evaluate the current state and equity level of DOAHPS in China, as well as to explore the main factors affecting DOAHPS’ current state and equity level.

Methods

This study analyzed the DOAHPS data from the "Survey on Chinese Residents' Health Service Demands in the New Era", which included 1542 older adults aged 65 and older. Relationships between evaluation indicators of DOAHPS were explored using Structural Equation Modeling (SEM). The Weighted TOPSIS method and Logistic regression (LR) were used to analyze the current state and factors impacting DOAHPS. The equity level of DOAHPS’ allocation among different older adult groups and its influencing factors were determined using the Rank Sum Ratio (RSR) method and T Theil index.

Results

The evaluation score for DOAHPS was 42.57 ± 1.51. Health status, health literacy and behavior were positively correlated with DOAHPS (r = 0.40, 0.38; P < 0.05). The LR results revealed that the most significant determinants of DOAHPS were sex, residence, education level and pre-retirement occupation (all P < 0.05). The number of older adults with very poor, poor, general, high and very high level health promotion service demands accounted for 2.27%, 28.60%, 53.05%, 15.43% and 0.65%, respectively. The total T Theil index of DOAHPS was 2.7433*10–4, and the intra-group difference contribution rate exceeded 72%.

Conclusions

Compared to the maximum level, the total DOAHPS level was found to be moderate, although the demands of urban seniors with higher levels of education may be substantially greater. The observed inequities in the allocation of DOAHPS were primarily related to differences in education level and pre-retirement occupation within group. To better address health promotion services for older adults, policymakers could target older males with low education who reside in rural regions.
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

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

Immunotherapy 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

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

Androgen 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

Extracellular 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

The 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

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

Prone 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

Background

Roughly 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.

Methods

Using 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.

Results

Genes 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.

Conclusions

Our 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

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

In 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

Many 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.
Mindfulness among lebanese university students and its indirect effect between mental health and wellbeing
Authors: Bitar Zeinab , Rogoza Radosław , Hallit Souheil , Obeid Sahar
Published: April 2023

Background

University students are a high-risk population for developing mental health issues. Mindfulness, the non-judgmental awareness of the present moment, has an effective role in numerous psychological contexts among students. However, no previous studies have investigated the association between mindfulness, mental health and wellbeing among Lebanese university students. Therefore, this study aimed to assess the mediating effect of mindfulness in the association between mental health and wellbeing in this population.

Methods

This cross-sectional study enrolled 363 Lebanese university students recruited through convenience sampling (July-September 2021). The Wellbeing Index Scale, Lebanese Anxiety Scale, Patient Health Questionnaire and Freiburg Mindfulness Inventory were used to assess subjective well-being, anxiety, depression and mindfulness respectively.

Results

Our findings showed that higher mindfulness (Beta = 0.18; p < 0.001) was significantly correlated with a higher wellbeing, whereas more depression (Beta=-0.36; p < 0.001) was significantly associated with a lower wellbeing. The results of the indirect effect analysis showed that mindfulness mediated the association between anxiety and wellbeing and between depression and wellbeing. Higher anxiety/depression were significantly associated with lower mindfulness and a lower wellbeing (direct effect). Moreover, higher mindfulness was significantly associated with a higher wellbeing.

Conclusion

Mindfulness is associated with improved wellbeing and plays an indirect role between mental health issues and wellbeing. Our results suggest that mindfulness presents an adaptive approach and coping method associated with improved students’ wellbeing.
Stigma towards people with tuberculosis: a cross-cultural adaptation and validation of a scale in Indonesia
Authors: Fuady Ahmad , Arifin Bustanul , Yunita Ferdiana , Rauf Saidah , Fitriangga Agus , Sugiharto Agus , Yani Finny Fitry , Nasution Helmi Suryani , Putra IWayan Gede Artawan Eka , Mansyur Muchtaruddin , Wingfield Tom
Published: April 2023

Introduction

Tuberculosis (TB) remains a highly stigmatised disease that can cause or exacerbate mental health disorders. Despite increased awareness of the importance of reducing TB stigma, validated tools to measure TB stigma remain scarce. This study aimed to culturally adapt and validate the Van Rie TB Stigma Scale in Indonesia, a country with the second largest TB incidence worldwide.

Methods

We validated the scale in three phases: translation, cultural adaptation, and psychometric evaluation. We invited diverse experts to an interdisciplinary panel for the cross-cultural adaptation, then performed a psychometric evaluation of the scale: exploratory and confirmatory factor analyses, reliability analysis, and correlation analysis with Patient Health Questionnaire 9 [PHQ-9].

Results

We culturally adapted the original scale's language and content during the translation and cultural adaptation phases. After psychometric evaluation with 401 participants in seven provinces of Indonesia, we removed two items. The new scale had two forms: (A) patient and (B) community perspective forms. Both forms had good internal consistency, with respective Cronbach's alpha values of 0.738 and 0.807. We identified three loading factors in Form A (disclosure, isolation, and guilty) and two loading factors in Form B (isolation and distancing). The scale showed correlation with PHQ-9 (Form A, rs = 0.347,p < 0.001; Form B, rs = 0).

Conclusions

The culturally adapted Indonesian version of Van Rie's TB Stigma Scale is comprehensive, reliable, internally consistent, and valid. The scale is now ready for applied scale-up in research and practice to measure TB-stigma and evaluate the impact of TB-stigma reduction interventions in Indonesia.
Functions of N6-methyladenosine in cancer metabolism: from mechanism to targeted therapy
Authors: He Jiayi , Liu Furong , Zhang Zhanguo
Published: April 2023

N6-methyladenosine (m6A) is the most abundant modification of eukaryotic mRNA and is involved in almost every stage of RNA metabolism. The m6A modification on RNA has been demonstrated to be a regulator of the occurrence and development of a substantial number of diseases, especially cancers. Increasing evidence has shown that metabolic reprogramming is a hallmark of cancer and is crucial for maintaining the homeostasis of malignant tumors. Cancer cells rely on altered metabolic pathways to support their growth, proliferation, invasion and metastasis in an extreme microenvironment. m6A regulates metabolic pathways mainly by either directly acting on metabolic enzymes and transporters or indirectly influencing metabolism-related molecules. This review discusses the functions of the m6A modification on RNAs, its role in cancer cell metabolic pathways, the possible underlying mechanisms of its effects and the implication of this modification in cancer therapy.
Redisposition of apiosporous genera Induratia and Muscodor in the Xylariales, following the discovery of an authentic strain of Induratia apiospora
Authors: Cedeño-Sanchez Marjorie , Schiefelbein Rahel , Stadler Marc , Voglmayr Hermann , Bensch Konstanze , Lambert Christopher
Published: April 2023

Background

The genus Induratia is based on Induratia apiospora, a xylarialean pyrenomycete from New Zealand with clypeate uniperitheciate stromata, hyaline apiospores and a nodulisporium-like anamorph. However, because of the lack of DNA data from the generic type, its phylogenetic affinities have remained unresolved. Recently, two fungal species with teleomorphs strikingly similar to Induratia were discovered in Thailand. However, they did not produce an anamorph and were found to be phylogenetically close to the species classified within the hyphomycete genus Muscodor, which was described after Induratia. Therefore, in 2020 the species of Muscodor were transferred to Induratia, and a new family Induratiaceae was proposed.

Results

We have encountered an unpublished ex-holotype strain of Induratia apiospora among the holdings of the ATCC collection, enabling detailed morphological and molecular phylogenetic investigations. We observed the characteristic nodulisporium-like anamorph described in the original publication. Phylogenetic analyses of multigene sequence data revealed a close relationship of Induratia apiospora to the Barrmaeliaceae, while a close relationship to the Induratia species formerly classified within Muscodor was rejected.

Conclusions

We here classify Induratia apiospora within the Barrmaeliaceae and consider Induratiaceae to be synonymous with the former. As the holotype specimen of Induratia apiospora is apparently lost, an isotype specimen from WSP is selected as lectotype. We also propose that the genus Muscodor is resurrected within the Xylariaceae, and formally transfer several Induratia species to Muscodor.