bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical profile and treatment outcomes of idiopathic intracranial hypertension: a multicenter study from Korea
Authors: Cho Kyung-Hee , Baek Seol-Hee , Kim Sung-Hee , Kim Byung-Su , Sohn Jong-Hee , Chu Min Kyung , Kang Mi-Kyoung , Mo Hee Jung , Lee Sang-Hwa , Park Hong-Kyun , Cho Soohyun , Oh Sun-Young , Seo Jong-Geun , Lee Wonwoo , Lee Ju-Young , Lee Mi Ji , Cho Soo-Jin
Published: June 2024

Background

Currently, there is a relative lack of detailed reports regarding clinical presentation and outcome of idiopathic intracranial hypertension in Asians. This study aims to describe the clinical features and treatment outcomes of Korean patients with idiopathic intracranial hypertension.

Methods

We prospectively recruited patients with idiopathic intracranial hypertension from one hospital and retrospectively analyzed the medical records of 11 hospitals in Korea. We collected data regarding preceding medical conditions or suspected medication exposure, headache phenotypes, other associated symptoms, detailed neuroimaging findings, treatments, and outcomes after 1–2 and 3–6 months of treatment.

Results

Fifty-nine (83.1% women) patients were included. The mean body mass index was 29.11 (standard deviation, 5.87) kg/m2; only 27 patients (45.8%) had a body mass index of ≥ 30 kg/m2. Fifty-one (86.4%) patients experienced headaches, patterns of which included chronic migraine (15/51 [29.4%]), episodic migraine (8/51 [15.7%]), probable migraine (4/51 [7.8%]), chronic tension-type headache (3/51 [5.9%]), episodic tension-type headache (2/51 [3.9%]), probable tension-type headache (2/51 [3.9%]), and unclassified (17/51 [33.3%]). Medication overuse headache was diagnosed in 4/51 (7.8%) patients. After 3–6 months of treatment, the intracranial pressure normalized in 8/32 (25.0%), improved in 17/32 (53.1%), no changed in 7/32 (21.9%), and worsened in none. Over the same period, headaches remitted or significantly improved by more than 50% in 24/39 patients (61.5%), improved less than 50% in 9/39 (23.1%), and persisted or worsened in 6/39 (15.4%) patients.

Conclusion

Our findings suggest that the features of Asian patients with idiopathic intracranial hypertension may be atypical (i.e., less likely obese, less female predominance). A wide spectrum of headache phenotypes was observed. Medical treatment resulted in overall favorable short-term outcomes; however, the headaches did not improve in a small proportion of patients.
Computer-vision analysis of craniofacial dysmorphology in 22q11.2 deletion syndrome and psychosis spectrum disorders
Authors: Roalf David R. , McDonald-McGinn Donna M. , Jee Joelle , Krall Mckenna , Crowley T. Blaine , Moberg Paul J. , Kohler Christian , Calkins Monica E. , Crow Andrew J.D. , Fleischer Nicole , Gallagher R. Sean , Gonzenbach Virgilio , Clark Kelly , Gur Ruben C. , McClellan Emily , McGinn Daniel E. , Mordy Arianna , Ruparel Kosha , Turetsky Bruce I. , Shinohara Russell T. , White Lauren , Zackai Elaine , Gur Raquel E.
Published: June 2024

Background

Minor physical anomalies (MPAs) are congenital morphological abnormalities linked to disruptions of fetal development. MPAs are common in 22q11.2 deletion syndrome (22q11DS) and psychosis spectrum disorders (PS) and likely represent a disruption of early embryologic development that may help identify overlapping mechanisms linked to psychosis in these disorders.

Methods

Here, 2D digital photographs were collected from 22q11DS (n = 150), PS (n = 55), and typically developing (TD; n = 93) individuals. Photographs were analyzed using two computer-vision techniques: (1) DeepGestalt algorithm (Face2Gene (F2G)) technology to identify the presence of genetically mediated facial disorders, and (2) Emotrics—a semi-automated machine learning technique that localizes and measures facial features.

Results

F2G reliably identified patients with 22q11DS; faces of PS patients were matched to several genetic conditions including FragileX and 22q11DS. PCA-derived factor loadings of all F2G scores indicated unique and overlapping facial patterns that were related to both 22q11DS and PS. Regional facial measurements of the eyes and nose were smaller in 22q11DS as compared to TD, while PS showed intermediate measurements.

Conclusions

The extent to which craniofacial dysmorphology 22q11DS and PS overlapping and evident before the impairment or distress of sub-psychotic symptoms may allow us to identify at-risk youths more reliably and at an earlier stage of development.
Cytotoxic effects of the cigarette smoke extract of heated tobacco products on human oral squamous cell carcinoma: the role of reactive oxygen species and CaMKK2
Authors: Kagemichi Nagao , Umemura Masanari , Ishikawa Soichiro , Iida Yu , Takayasu Shota , Nagasako Akane , Nakakaji Rina , Akimoto Taisuke , Ohtake Makoto , Horinouchi Takahiro , Yamamoto Tetsuya , Ishikawa Yoshihiro
Published: June 2024

Background

The increasing prevalence of heated tobacco products (HTPs) has heightened concerns regarding their potential health risks. Previous studies have demonstrated the toxicity of cigarette smoke extract (CSE) from traditional tobacco’s mainstream smoke, even after the removal of nicotine and tar. Our study aimed to investigate the cytotoxicity of CSE derived from HTPs and traditional tobacco, with a particular focus on the role of reactive oxygen species (ROS) and intracellular Ca2+.

Methods

A human oral squamous cell carcinoma (OSCC) cell line, HSC-3 was utilized. To prepare CSE, aerosols from HTPs (IQOS) and traditional tobacco products (1R6F reference cigarette) were collected into cell culture media. A cell viability assay, apoptosis assay, western blotting, and Fluo-4 assay were conducted. Changes in ROS levels were measured using electron spin resonance spectroscopy and the high-sensitivity 2ʹ,7ʹ-dichlorofluorescein diacetate assay. We performed a knockdown of calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) by shRNA lentivirus in OSCC cells.

Results

CSE from both HTPs and traditional tobacco exhibited cytotoxic effects in OSCC cells. Exposure to CSE from both sources led to an increase in intracellular Ca2+ concentration and induced p38 phosphorylation. Additionally, these extracts prompted cell apoptosis and heightened ROS levels. N-acetylcysteine (NAC) mitigated the cytotoxic effects and p38 phosphorylation. Furthermore, the knockdown of CaMKK2 in HSC-3 cells reduced cytotoxicity, ROS production, and p38 phosphorylation in response to CSE.

Conclusion

Our findings suggest that the CSE from both HTPs and traditional tobacco induce cytotoxicity. This toxicity is mediated by ROS, which are regulated through Ca2+ signaling and CaMKK2 pathways.

Graphical Abstract
0.75% ropivacaine may be a suitable drug in pregnant women undergoing urgent cesarean delivery during labor analgesia period
Authors: Men Xin , Wang Qian , Dong Jia-fu , Chen Pei , Qiu Xiao-xiao , Han Yin-qiu , Wang Wei-long , Zhou Jin , Shou Hong-yan , Zhou Zhen-feng
Published: June 2024

Background

3% chloroprocaine (CP) has been reported as the common local anesthetic used in pregnant women undergoing urgent cesarean delivery during labor analgesia period. However, 0.75% ropivacaine is considered a promising and effective alternative. Therefore, we conducted a randomized controlled trial to compare the effectiveness and safety of 0.75% ropivacaine with 3% chloroprocaine for extended epidural anesthesia in pregnant women.

Methods

We conducted a double-blind, randomized, controlled, single-center study from November 1, 2022, to April 30, 2023. We selected forty-five pregnant women undergoing urgent cesarean delivery during labor analgesia period and randomized them to receive either 0.75% ropivacaine or 3% chloroprocaine in a 1:1 ratio. The primary outcome was the time to loss of cold sensation at the T4 level.

Results

There was a significant difference between the two groups in the time to achieve loss of cold sensation (303, 95%CI 255 to 402 S vs. 372, 95%CI 297 to 630 S, p = 0.024). There was no significant difference the degree of motor block (p = 0.185) at the Th4 level. Fewer pregnant women required additional local anesthetics in the ropivacaine group compared to the chloroprocaine group (4.5% VS. 34.8%, p = 0.011). The ropivacaine group had lower intraoperative VAS scores (p = 0.023) and higher patient satisfaction scores (p = 0.040) than the chloroprocaine group. The incidence of intraoperative complications was similar between the two groups, and no serious complications were observed.

Conclusions

Our study found that 0.75% ropivacaine was associated with less intraoperative pain treatment, higher patient satisfaction and reduced the onset time compared to 3% chloroprocaine in pregnant women undergoing urgent cesarean delivery during labor analgesia period. Therefore, 0.75% ropivacaine may be a suitable drug in pregnant women undergoing urgent cesarean delivery during labor analgesia period.

Clinical trial number and registry URL

The registration number: ChiCTR2200065201; http://www.chictr.org.cn, Principal investigator: MEN, Date of registration: 31/10/2022.
The effects of refractive status on the outcomes of strabismus surgery in patients with esotropia
Authors: Rajavi Zhale , Khorrame Zahra , Ashrafi Sadra
Published: June 2024

Background

The success of the strabismus surgery can hinge on several factors. One of these factors is refractive condition like hyperopia or myopia. Our study seeks to evaluate the surgical outcomes in patients with esotropia and myopia.

Methods

This case-control study encompassed all surgical cases of esotropia at Torfe and Negah Hospital between 2016 and 2021, which satisfied our specified inclusion criteria. The initial variables from electronic medical records were collected, including demographic, clinical, and surgery-related factors. At the final follow-up appointment, the level of eye deviation, both at distance and near, was recorded. We considered the operation a “success” for patients with a post-surgery distance eye deviation of 10(Pd) or less. Patients with greater deviation were classified as surgery failure. Statistical analyses were executed using SPSS software (version 16.0), and a P-value less than 0.05 was considered significant.

Results

Of the 194 patients evaluated, 112 were incorporated into the study. Surgical failure was observed in 14.29% of myopic patients, 29.79% of hyperopic patients, and 31.82% of emmetropic patients. The myopia group displayed a 0.19 odd ratio for surgical failure compared to the combined hyperopia and emmetropia groups, not statistically significant (OR: 0.19, CI 95%: 0.03–1.02). Additionally, patients diagnosed with Lateral Rectus Under-action were found to be 6.85 times more likely to experience surgery failure(OR: 6.85, CI 95%: 1.52–30.94). An elevated risk of surgical failure was also identified in patients who underwent Inferior Oblique Weakening procedure, indicated by a 3.77-fold increase in the odds ratio for failure(OR: 3.77, CI 95%: 1.08–13.17).

Conclusion

In our study, despite numerical disparities, there was no statistical difference among the success rates of all esotropia patients with different refractive errors. The patients with LRUA or IOOA showed lower success rates. Myopic patients had higher post-op overcorrection with lower reoperation rates compared to hyperopic or emmetropic patients.
Associations among drug acquisition and use behaviors, psychosocial attributes, and opioid-involved overdoses
Authors: Swartz James A. , Zhao Peipei , Jacobucci Ross , Watson Dennis P. , Mackesy-Amiti Mary Ellen , Franceschini Dana , Jimenez A. David
Published: June 2024

Aims

This study sought to develop and assess an exploratory model of how demographic and psychosocial attributes, and drug use or acquisition behaviors interact to affect opioid-involved overdoses.

Design

We conducted exploratory and confirmatory factor analysis (EFA/CFA) to identify a factor structure for ten drug acquisition and use behaviors. We then evaluated alternative structural equation models incorporating the identified factors, adding demographic and psychosocial attributes as predictors of past-year opioid overdose.

Setting and participants

We used interview data collected for two studies recruiting opioid-misusing participants receiving services from a community-based syringe services program. The first investigated current attitudes toward drug-checking (N = 150). The second was an RCT assessing a telehealth versus in-person medical appointment for opioid use disorder treatment referral (N = 270).

Measurements

Demographics included gender, age, race/ethnicity, education, and socioeconomic status. Psychosocial measures were homelessness, psychological distress, and trauma. Self-reported drug-related risk behaviors included using alone, having a new supplier, using opioids with benzodiazepines/alcohol, and preferring fentanyl. Past-year opioid-involved overdoses were dichotomized into experiencing none or any.

Findings

The EFA/CFA revealed a two-factor structure with one factor reflecting drug acquisition and the second drug use behaviors. The selected model (CFI = .984, TLI = .981, RMSEA = .024) accounted for 13.1% of overdose probability variance. A latent variable representing psychosocial attributes was indirectly associated with an increase in past-year overdose probability (β = .234, p = .001), as mediated by the EFA/CFA identified latent variables: drug acquisition (β = .683, p < .001) and drug use (β = .567, p = .001). Drug use behaviors (β = .287, p = .04) but not drug acquisition (β = .105, p = .461) also had a significant, positive direct effect on past-year overdose. No demographic attributes were significant direct or indirect overdose predictors.

Conclusions

Psychosocial attributes, particularly homelessness, increase the probability of an overdose through associations with risky drug acquisition and drug-using behaviors. Further research is needed to replicate these findings with populations at high-risk of an opioid-related overdose to assess generalizability and refine the metrics used to assess psychosocial characteristics.
End-expiratory lung volumes as a potential indicator for COVID-19 associated acute respiratory distress syndrome: a retrospective study
Authors: Hao Shengyu , Wei Yilin , Wang Yuxian , Muhetaer Yaxiaerjiang , Zhou Chujun , Qiong Songjie , Jiang Pan , Zhong Ming
Published: June 2024

Background

End-expiratory lung volume (EELV) has been observed to decrease in acute respiratory distress syndrome (ARDS). Yet, research investigating EELV in patients with COVID-19 associated ARDS (CARDS) remains limited. It is unclear whether EELV could serve as a potential metric for monitoring disease progression and identifying patients with ARDS at increased risk of adverse outcomes.

Study design and methods

This retrospective study included mechanically ventilated patients diagnosed with CARDS during the initial phase of epidemic control in Shanghai. EELV was measured using the nitrogen washout-washin technique within 48 h post-intubation, followed by regular assessments every 3–4 days. Chest CT scans, performed within a 24-hour window around each EELV measurement, were analyzed using AI software. Differences in patient demographics, clinical data, respiratory mechanics, EELV, and chest CT findings were assessed using linear mixed models (LMM).

Results

Out of the 38 patients enrolled, 26.3% survived until discharge from the ICU. In the survivor group, EELV, EELV/predicted body weight (EELV/PBW) and EELV/predicted functional residual capacity (EELV/preFRC) were significantly higher than those in the non-survivor group (survivor group vs. non-survivor group: EELV: 1455 vs. 1162 ml, P = 0.049; EELV/PBW: 24.1 vs. 18.5 ml/kg, P = 0.011; EELV/preFRC: 0.45 vs. 0.34, P = 0.005). Follow-up assessments showed a sustained elevation of EELV/PBW and EELV/preFRC among the survivors. Additionally, EELV exhibited a positive correlation with total lung volume and residual lung volume, while demonstrating a negative correlation with lesion volume determined through chest CT scans analyzed using AI software.

Conclusion

EELV is a useful indicator for assessing disease severity and monitoring the prognosis of patients with CARDS.
Outcome after total ankle replacement or ankle arthrodesis in end-stage ankle osteoarthritis on the basis of german-wide data: a retrospective comparative study over 10 years
Authors: Kostuj Tanja , Hönning Alexander , Mittelmeier Wolfram , Malzahn Jürgen , H. Baums Mike , Osmanski-Zenk Katrin
Published: June 2024

Background

In symptomatic end-stage osteoarthritis of the ankle joint, total ankle replacement and ankle arthrodesis are the two primary surgical options for patients for whom conservative treatment fails. Published revision rates are often biased and difficult to compare. In this study, unplanned reoperation rates and revision rates were determined for both surgical interventions based on a large dataset, and risk factors for unplanned reoperations were identified.

Methods

German-wide health data of the largest German health-care insurance carrier between 2001 and 2012 were retrospectively analyzed, and unplanned reoperation rates within 10 years were determined for index surgeries conducted in 2001 and 2002. Unplanned reoperation rates within 5 years for index surgeries conducted in 2001/2002 were compared to index surgeries conducted in 2006/2007. Multivariate logistic regression was used to identify risk factors for unplanned reoperations.

Results

After ankle arthrodesis, 19% (95% confidence interval [CI], 16–22%) of 741 patients needed to undergo an unplanned reoperation within ten years. After total ankle replacement, the unplanned reoperation rate was 38% [95% CI, 29–48%] among 172 patients. For initial surgeries conducted at a later date, unplanned reoperation rates within five years were 21% [95% CI, 19–24%] for 1,168 ankle arthrodesis patients and 23% [95% CI, 19–28%] for 561 total ankle replacement patients. Significant risk factors for unplanned reoperations after ankle arthrodesis in the initial cohort were age < 50 years (odds ratio [OR] = 4.65 [95% CI 1.10;19.56]) and osteoporosis (OR = 3.72 [95% CI, 1.06;13.11]); after total ankle replacement, they were osteoporosis (OR = 2.96 [95% CI, 1.65;5.31]), Patient Clinical Complexity Level (PCCL) grade 3 (OR = 2.19 [95% CI, 1.19;4.03]), PCCL grade 4 (OR = 2.51 [95% CI, 1.22;5.17]) and diabetes mellitus (OR = 2.48 [95% CI, 1.33;4.66]). Kaplan-Meier analyses including 1,525 ankle arthrodesis patients and 644 total ankle replacement patients revealed an average unplanned reoperation-free time of approximately 17 years for both procedures.

Conclusions

Similar revision rates and unplanned reoperation rates for both procedures in the later-date cohort can likely be attributed to a learning curve for surgeons as well as advances in implant design. This analysis of billing health insurance data supports an increase in total ankle replacement surgeries.
Skill development practice-related challenges, and associated factors among nursing students
Authors: Ataro Bizuayehu Atinafu , Addisie Almaz , Hardido Temesgen Geta , Bolado Getachew Nigussie , Bilate Dawit Simeon , Leka Yakob Lencha , Bezabih Beskut
Published: June 2024

Background

Nurse students reportedly face lots of challenges during skill development practice in health institutions. However, the prevalence of challenges and factors associated aren’t well understood yet.

Objective

The objective of the study was to identify the challenges experienced by nursing students in health institutions during skill development practice.

Method

A cross-sectional study was employed on the participants selected using a simple random sampling technique. The data was cleaned using Epi-data and exported to SPSS for analysis. Logistic regression analysis and correlation analysis were carried out to identify the associated factors.

Result

The participants are more challenged by instructor factors (43.6%) and facility factors (40%). The prevalence of the challenge was 16.9%. Substance use and learning institutions are found to be independent predictors. A negative correlation was identified between the total challenge score and the overall competency score.

Conclusion

The determined nursing students’ challenges are strong enough to affect the quality of education; therefore, it is essential to plan and improve the students’ integrated supportive supervision.
Preovulatory follicular fluid secretome added to in vitro maturation medium influences the metabolism of equine cumulus-oocyte complexes
Authors: Luis-Calero Marcos , Ortiz-Rodríguez José Manuel , Fernández-Hernández Pablo , Muñoz-García Carmen Cristina , Pericuesta Eva , Gutiérrez-Adán Alfonso , Marinaro Federica , Embade Nieves , Conde Ricardo , Bizkarguenaga Maider , Millet Óscar , González-Fernández Lauro , Macías-García Beatriz
Published: June 2024

Background

In vitro embryo production is a highly demanded reproductive technology in horses, which requires the recovery (in vivo or post-mortem) and in vitro maturation (IVM) of oocytes. Oocytes subjected to IVM exhibit poor developmental competence compared to their in vivo counterparts, being this related to a suboptimal composition of commercial maturation media. The objective of this work was to study the effect of different concentrations of secretome obtained from equine preovulatory follicular fluid (FF) on cumulus-oocyte complexes (COCs) during IVM. COCs retrieved in vivo by ovum pick up (OPU) or post-mortem from a slaughterhouse (SLA) were subjected to IVM in the presence or absence of secretome (Control: 0 µg/ml, S20: 20 µg/ml or S40: 40 µg/ml). After IVM, the metabolome of the medium used for oocyte maturation prior (Pre-IVM) and after IVM (Post-IVM), COCs mRNA expression, and oocyte meiotic competence were analysed.

Results

IVM leads to lactic acid production and an acetic acid consumption in COCs obtained from OPU and SLA. However, glucose consumption after IVM was higher in COCs from OPU when S40 was added (Control Pre-IVM vs. S40 Post-IVM: 117.24 ± 7.72 vs. 82.69 ± 4.24; Mean µM ± SEM; p < 0.05), while this was not observed in COCs from SLA. Likewise, secretome enhanced uptake of threonine (Control Pre-IVM vs. S20 Post-IVM vs. S40 Post-IVM: 4.93 ± 0.33 vs. 3.04 ± 0.25 vs. 2.84 ± 0.27; Mean µM ± SEM; p < 0.05) in COCs recovered by OPU. Regarding the relative mRNA expression of candidate genes related to metabolism, Lactate dehydrogenase A (LDHA) expression was significantly downregulated when secretome was added during IVM at 20–40 µg/ml in OPU-derived COCs (Control vs. S20 vs. S40: 1.77 ± 0.14 vs. 1 ± 0.25 vs. 1.23 ± 0.14; fold change ± SEM; p < 0.05), but not in SLA COCs.

Conclusions

The addition of secretome during in vitro maturation (IVM) affects the gene expression of LDHA, glucose metabolism, and amino acid turnover in equine cumulus-oocyte complexes (COCs), with diverging outcomes observed between COCs retrieved using ovum pick up (OPU) and slaughterhouse-derived COCs (SLA).
Monitoring measurable residual disease in paediatric acute lymphoblastic leukaemia using immunoglobulin gene clonality based on next-generation sequencing
Authors: Ahn Won Kee , Yu Kyunghee , Kim Hongkyung , Lee Seung-Tae , Choi Jong Rak , Han Jung Woo , Lyu Chuhl Joo , Hahn Seungmin , Shin Saeam
Published: June 2024

Background

Assessment of measurable residual disease (MRD) is an essential prognostic tool for B-lymphoblastic leukaemia (B-ALL). In this study, we evaluated the utility of next-generation sequencing (NGS)–based MRD assessment in real-world clinical practice.

Method

The study included 93 paediatric patients with B-ALL treated at our institution between January 2017 and June 2022. Clonality for IGH or IGK rearrangements was identified in most bone marrow samples (91/93, 97.8%) obtained at diagnosis.

Results

In 421 monitoring samples, concordance was 74.8% between NGS and multiparameter flow cytometry and 70.7% between NGS and reverse transcription-PCR. Elevated quantities of clones of IGH alone (P < 0.001; hazard ratio [HR], 22.2; 95% confidence interval [CI], 7.1–69.1), IGK alone (P = 0.011; HR, 5.8; 95% CI, 1.5–22.5), and IGH or IGK (P < 0.001; HR, 7.2; 95% CI, 2.6–20.0) were associated with an increased risk of relapse. Detection of new clone(s) in NGS was also associated with inferior relapse-free survival (P < 0.001; HR, 18.1; 95% CI, 3.0–108.6). Multivariable analysis confirmed age at diagnosis, BCR::ABL1-like mutation, TCF3::PBX1 mutation, and increased quantity of IGH or IGK clones during monitoring as unfavourable factors.

Conclusion

In conclusion, this study highlights the usefulness of NGS-based MRD as a routine assessment tool for prognostication of paediatric patients with B-ALL.
Tumor-associated characteristics and immune dysregulation in nasopharyngeal carcinoma under the regulation of m7G-related tumor microenvironment cells
Authors: Long Zhen , Li Xiaochen , Deng Wenmin , Tan Yan , Liu Jie
Published: June 2024

Background

Nasopharyngeal carcinoma (NPC) is a type of malignant tumor with high morbidity. Aberrant levels of N7-methylguanosine (m7G) are closely associated with tumor progression. However, the characteristics of the tumor microenvironment (TME) in NPC associated with m7G modification remain unclear.

Methods

A total of 68,795 single cells from single-cell RNA sequencing data derived from 11 NPC tumor samples and 3 nasopharyngeal lymphatic hyperplasia (NLH) samples were clustered using a nonnegative matrix factorization algorithm according to 61 m7G RNA modification regulators.

Results

The m7G regulators were found differential expression in the TME cells of NPC, and most m7G-related immune cell clusters in NPC tissues had a higher abundance compared to non-NPC tissues. Specifically, m7G scores in the CD4+ and CD8+ T cell clusters were significantly lower in NPC than in NLH. T cell clusters differentially expressed immune co-stimulators and co-inhibitors. Macrophage clusters differentially expressed EIF4A1, and high EIF4A1 expression was associated with poor survival in patients with head and neck squamous carcinoma. EIF4A1 was upregulated in NPC tissues compared to the non-NPC tissues and mainly expressed in CD86+ macrophages. Moreover, B cell clusters exhibited tumor biological characteristics under the regulation of m7G-related genes in NPC. The fibroblast clusters interacted with the above immune cell clusters and enriched tumor biological pathways, such as FGER2 signaling pathway. Importantly, there were correlations and interactions through various ligand-receptor links among epithelial cells and m7G-related TME cell clusters.

Conclusion

Our study revealed tumor-associated characteristics and immune dysregulation in the NPC microenvironment under the regulation of m7G-related TME cells. These results demonstrated the underlying regulatory roles of m7G in NPC.
Which factors are associated with adverse prognosis in multiple myeloma patients after surgery? - preliminary establishment and validation of the nomogram
Authors: Liu Jun-Peng , Xu Zi-Yu , Wu Yue , Shi Xiang-Jun , Shi Ming , Li Meng , Du Xin-Ru , Yao Xing-Chen
Published: June 2024

Background

To investigate the prognosis of patients with Multiple Myeloma (MM) after surgery, analyze the risk factors leading to adverse postoperative outcomes, and establish a nomogram.

Methods

Clinical data from 154 patients with MM who underwent surgery at our institution between 2007 and 2019 were retrospectively analyzed. Assessing and comparing patients’ pain levels, quality of life, and functional status before and after surgery (P < 0.05) were considered statistically significant. The Kaplan-Meier survival curve was used to estimate the median survival time. Adverse postoperative outcomes were defined as worsened symptoms, lesion recurrence, complication grade ≥ 2, or a postoperative survival period < 1 year. Logistic regression analysis was used to determine the prognostic factors. Based on the logistic regression results, a nomogram predictive model was developed and calibrated.

Results

Postoperative pain was significantly alleviated in patients with MM, and there were significant improvements in the quality of life and functional status (P < 0.05). The median postoperative survival was 41 months. Forty-nine patients (31.8%) experienced adverse postoperative outcomes. Multivariate logistic regression analysis identified patient age, duration of MM, International Staging System, preoperative Karnofsky Performance Status, and Hb < 90 g/L as independent factors influencing patient prognosis. Based on these results, a nomogram was constructed, with a C-index of 0.812. The calibration curve demonstrated similarity between the predicted and actual survival curves. Decision curve analysis favored the predictive value of the model at high-risk thresholds from 10% to-69%.

Conclusion

This study developed a nomogram risk prediction model to assist in providing quantifiable assessment indicators for preoperative evaluation of surgical risk.
The effect of Mycobacterium tuberculosis treatment on thrombelastography-assessed haemostasis: a prospective cohort study
Authors: Lorentsson Hans Johan Niklas , Clausen Christina R. , Faurholt-Jepsen Daniel , Hansen Katrine Bagge , Jensen Sidse Graff , Krogh-Madsen Rikke , Hagelqvist Per G. , Johansson Pär I. , Vilsbøll Tina , Knop Filip K. , Ravn Pernille
Published: June 2024

Background and objective

Tuberculosis disease (TB) and tuberculosis infection (TBI) have been associated with increased risk of cardiovascular disease which may be connected to infection-related haemostatic changes. It is unknown if treatment of Mycobacterium tuberculosis influences haemostasis. Here, we assessed if TB or TBI treatment affects thrombelastography (TEG)-assessed haemostasis.

Methods

Individuals with TB or TBI were included from a TB outpatient clinic in Copenhagen, Denmark. Patients treated with antithrombotic medication or systemic immunosuppressants were excluded. TEG analysis was performed before and after TB/TBI treatment using the TEG®6s analyser to provide data on the reaction time of clot initiation (R) (min), the speed of clot formation (K) (min) and clot build-up (Angle) (°), maximum clot strength (MA) (mm), and clot breakdown/fibrinolysis (LY30) (%). Differences in TEG were assessed using paired t tests.

Results

We included eleven individuals with TB with median [interquartile range] [IQR] age 52 [32] years and mean (standard deviation) (SD) body mass index (BMI) 24.7 (6.3) kg/m2 as well as 15 individuals with TBI with median [IQR] age 49 [25] years and BMI 26.0 (3.2) kg/m2. Treatment reduced MA for both TB (64.0 (6.3) vs. 57.9 (5.2) mm, p = 0.016) and TBI (61.3 (4.1) vs. 58.6 (5.0) mm, p = 0.023) whereas R, K, Angle and LY30 were unaffected.

Conclusion

TEG analysis showed that treatments of TB and TBI were associated with reduced MA which may indicate the existence of cardiovascular benefits from therapy.

Trial registration

Registered at ClinicalTrials.gov 05 April 2021 with registration number NCT04830462.
Forecast accuracy of demand for registered nurses and its determinants in South Korea
Authors: Jeong Suyong
Published: June 2024

Background

Despite the significance of demand forecasting accuracy for the registered nurse (RN) workforce, few studies have evaluated past forecasts.

Purpose

This paper examined the ex post accuracy of past forecasting studies focusing on RN demand and explored its determinants on the accuracy of demand forecasts.

Methods

Data were collected by systematically reviewing national reports or articles on RN demand forecasts. The mean absolute percentage error (MAPE) was measured for forecasting error by comparing the forecast with the actual demand (employed RNs). Nonparametric tests, the Mann‒Whitney test, and the Kruskal‒Wallis test were used to analyze the differences in the MAPE according to the variables, which are methodological and researcher factors.

Results

A total of 105 forecast horizons and 196 forecasts were analyzed. The average MAPE of the total forecast horizon was 34.8%. Among the methodological factors, the most common determinant affecting forecast accuracy was the RN productivity assumption. The longer the length of the forecast horizon was, the greater the MAPE was. The longer the length of the data period was, the greater the MAPE was. Moreover, there was no significant difference among the researchers’ factors.

Conclusions

To improve demand forecast accuracy, future studies need to accurately measure RN workload and productivity in a manner consistent with the real world.
Achieving research impact in medical research through collaboration across organizational boundaries: Insights from a mixed methods study in the Netherlands
Authors: van Oijen Jacqueline C. F. , van Dongen-Leunis Annemieke , Postma Jeroen , van Leeuwen Thed , Bal Roland
Published: June 2024

Background

In the Netherlands, university medical centres (UMCs) bear primary responsibility for conducting medical research and delivering highly specialized care. The TopCare program was a policy experiment lasting 4 years in which three non-academic hospitals received funding from the Dutch Ministry of Health to also conduct medical research and deliver highly specialized care in specific domains. This study investigates research collaboration outcomes for all Dutch UMCs and non-academic hospitals in general and, more specifically, for the domains in the non-academic hospitals participating in the TopCare program. Additionally, it explores the organizational boundary work employed by these hospitals to foster productive research collaborations.

Methods

A mixed method research design was employed combining quantitative bibliometric analysis of publications and citations across all Dutch UMCs and non-academic hospitals and the TopCare domains with geographical distances, document analysis and ethnographic interviews with actors in the TopCare program.

Results

Quantitative analysis shows that, over the period of study, international collaboration increased among all hospitals while national collaboration and single institution research declined slightly. Collaborative efforts correlated with higher impact scores, and international collaboration scored higher than national collaboration. A total of 60% of all non-academic hospitals’ publications were produced in collaboration with UMCs, whereas almost 30% of the UMCs’ publications were the result of such collaboration. Non-academic hospitals showed a higher rate of collaboration with the UMC that was nearest geographically, whereas TopCare hospitals prioritized expertise over geographical proximity within their specialized domains. Boundary work mechanisms adopted by TopCare hospitals included aligning research activities with organizational mindset (identity), bolstering research infrastructure (competence) and finding and mobilizing strategic partnerships with academic partners (power). These efforts aimed to establish credibility and attractiveness as collaboration partners.

Conclusions

Research collaboration between non-academic hospitals and UMCs, particularly where this also involves international collaboration, pays off in terms of publications and impact. The TopCare hospitals used the program’s resources to perform boundary work aimed at becoming an attractive and credible collaboration partner for academia. Local factors such as research history, strategic domain focus, in-house expertise, patient flows, infrastructure and network relationships influenced collaboration dynamics within TopCare hospitals and between them and UMCs.
Single cell transcriptome analysis identified a unique neutrophil type associated with Alzheimer’s disease
Authors: Zhang Xiaolin , He Guiqin , Hu Yixuan , Liu Boren , Xu Yuliang , Li Xia , Lv Xinyou , Li Jin
Published: June 2024

Background

Neutrophils play an essential role in Alzheimer’s disease (AD) pathology. However, the extent of their heterogeneity remains poorly explored, particularly in the context of developing novel therapies targeting these cells.

Results

We investigate the population structure of neutrophils purified from peripheral blood samples of AD mice. Utilizing single cell RNA sequencing, we comprehensively map neutrophil populations into six distinct clusters and find that the Neu-5 subset is specially enriched in AD mice. This subset exhibits fewer specific granules and a lower mature score. Gene ontology (GO) analysis reveals that genes involved in cytokine-mediated signaling are downregulated in the Neu-5 cluster. Furthermore, we identify the Ccrl2 gene is specifically upregulated in this subgroup, which is confirmed by flow cytometry in AD mice. Finally, immunohistochemical staining indicates that CCRL2 protein is increased in the brains of AD mice.

Conclusions

We identify a unique CCRL2 positive neutrophil cluster, that is specifically enriched in the peripheral blood of AD mice.
Discovery and characterization of novel jeilongviruses in wild rodents from Hubei, China
Authors: Gan Min , Hu Bing , Ding Qingwen , Zhang Nailou , Wei Jinbo , Nie Tao , Cai Kun , Zheng Zhenhua
Published: June 2024

The genus Jeilongvirus comprises non-segmented negative-stranded RNA viruses that are classified within the Paramyxoviridae family by phylogeny. Jeilongviruses are found in various reservoirs, including rodents and bats. Rodents are typical viral reservoirs with diverse spectra and zoonotic potential. Little is currently known about jeilongviruses in rodents from central China. The study utilized high-throughput and Sanger sequencing to obtain jeilongvirus genomes, including those of two novel strains (HBJZ120/CHN/2021 (17,468 nt) and HBJZ157/CHN/2021 (19,143 nt)) and three known viruses (HBXN18/CHN/2021 (19,212 nt), HBJZ10/CHN/2021 (19,700 nt), HBJM106/CHN/2021 (18,871 nt)), which were characterized by genome structure, identity matrix, and phylogenetic analysis. Jeilongviruses were classified into three subclades based on their topology, phylogeny, and hosts. Based on the amino acid sequence identities and phylogenetic analysis of the L protein, HBJZ120/CHN/2021 and HBJZ157/CHN/2021 were found to be strains rather than novel species. Additionally, according to specific polymerase chain reaction screening, the positive percentage of Beilong virus in Hubei was 6.38%, suggesting that Beilong virus, belonging to the Jeilongvirus genus, is likely to be widespread in wild rodents. The identification of novel strains further elucidated the genomic diversity of jeilongviruses. Additionally, the prevalence of jeilongviruses in Hubei, China, was profiled, establishing a foundation for the surveillance and early warning of emerging paramyxoviruses.
Impact of subtype C-specific amino acid variants on HIV-1 Tat-TAR interaction: insights from molecular modelling and dynamics
Authors: Gotora Piwai T. , Brown Keaghan , Martin Darius R. , van der Sluis Rencia , Cloete Ruben , Williams Monray E.
Published: June 2024

Background

HIV-1 produces Tat, a crucial protein for transcription, viral replication, and CNS neurotoxicity. Tat interacts with TAR, enhancing HIV reverse transcription. Subtype C Tat variants (C31S, R57S, Q63E) are associated with reduced transactivation and neurovirulence compared to subtype B. However, their precise impact on Tat-TAR binding is unclear. This study investigates how these substitutions affect Tat-TAR interaction.

Methods

We utilized molecular modelling techniques, including MODELLER, to produce precise three-dimensional structures of HIV-1 Tat protein variants. We utilized Tat subtype B as the reference or wild type, and generated Tat variants to mirror those amino acid variants found in Tat subtype C. Subtype C-specific amino acid substitutions were selected based on their role in the neuropathogenesis of HIV-1. Subsequently, we conducted molecular docking of each Tat protein variant to TAR using HDOCK, followed by molecular dynamic simulations.

Results

Molecular docking results indicated that Tat subtype B (TatWt) showed the highest affinity for the TAR element (-262.07), followed by TatC31S (-261.61), TatQ63E (-256.43), TatC31S/R57S/Q63E (-238.92), and TatR57S (-222.24). However, binding free energy analysis showed higher affinities for single variants TatQ63E (-349.2 ± 10.4 kcal/mol) and TatR57S (-290.0 ± 9.6 kcal/mol) compared to TatWt (-247.9 ± 27.7 kcal/mol), while TatC31S and TatC31S/R57SQ/63E showed lower values. Interactions over the protein trajectory were also higher for TatQ63E and TatR57S compared to TatWt, TatC31S, and TatC31S/R57SQ/63E, suggesting that modifying amino acids within the Arginine/Glutamine-rich region notably affects TAR interaction. Single amino acid mutations TatR57S and TatQ63E had a significant impact, while TatC31S had minimal effect. Introducing single amino acid variants from TatWt to a more representative Tat subtype C (TatC31S/R57SQ/63E) resulted in lower predicted binding affinity, consistent with previous findings.

Conclusions

These identified amino acid positions likely contribute significantly to Tat-TAR interaction and the differential pathogenesis and neuropathogenesis observed between subtype B and subtype C. Additional experimental investigations should prioritize exploring the influence of these amino acid signatures on TAR binding to gain a comprehensive understanding of their impact on viral transactivation, potentially identifying them as therapeutic targets.
Trends in the availability and prices of quality-assured tuberculosis drugs: a systematic analysis of Global Drug Facility Product Catalogs from 2001 to 2024
Authors: Kohler Stefan , Achar Jay , Mulder Christiaan , Sitali Norman , Paul Nicolas
Published: June 2024

Background

The Global Drug Facility (GDF) of the Stop TB Partnership was launched in 2001 with the goal of increasing access to quality-assured tuberculosis (TB) drugs and products. We aimed to describe the TB drugs and prices available from the GDF over time and to assess trends.

Methods

We searched the internet, including an internet archive, for past and recent GDF Product Catalogs and extracted the listed TB drugs and prices. We calculated the lowest price for the most common drug formulations assuming drugs with similar active pharmaceutical ingredients (APIs) are substitutes for each other. We assessed time trends in the TB drugs and prices offered by the GDF in univariable regressions over the longest possible period.

Results

We identified 43 different GDF Product Catalogs published between November 2001 and May 2024. These product catalogs included 122 single medicines (31 APIs), 28 fixed-dose combinations (9 API combinations), and 8 patient kits (8 API regimens and other materials). The number of TB drugs listed in the GDF Product Catalog increased from 9 (8 APIs) to 55 (32 APIs). The price decreased for 17, increased for 19, and showed no trend for 12 APIs. The price of 15 (53.6%) of 28 APIs used against drug-resistant TB decreased, including the price of drugs used in new treatment regimens. The decreasing price trend was strongest for linezolid (-16.60 [95% CI: -26.35 to -6.85] percentage points [pp] per year), bedaquiline (-12.61 [95% CI: -18.00 to -7.22] pp per year), cycloserine (-11.20 [95% CI: -17.40 to -4.99] pp per year), pretomanid (-10.47 [95% CI: -15.06 to -5.89] pp per year), and rifapentine (-10.46 [95% CI: -12.86 to -8.06] pp per year). The prices of 16 (61.5%) of 23 APIs for standard drug-susceptible TB treatment increased, including rifampicin (23.70 [95% CI: 18.48 to 28.92] pp per year), isoniazid (20.95 [95% CI: 18.96 to 22.95] pp per year), ethambutol (9.85 [95% CI: 8.83 to 10.88] pp per year), and fixed-dose combinations thereof.

Conclusions

The number of TB drugs available from the GDF has substantially increased during its first 23 years of operation. The prices of most APIs for new TB treatments decreased or remained stable. The prices of most APIs for standard drug-sensitive TB treatment increased.
Prognostic factors for long-term improvement in pain and disability among patients with persistent low back pain
Authors: Mihlberg Elin , Arnbak Bodil Al-Mashhadi
Published: June 2024

Background

Prognostic research in low back pain (LBP) is essential for understanding and managing the condition. This study aimed to, (1) describe the proportions with mild-moderate and severe pain and disability at baseline, 1-year and 4-year follow-up, and (2) investigate prognostic factors for improvement in pain and disability over 4 years in a cohort of secondary care LBP patients.

Methods

This was a secondary analysis of a cohort of patients with LBP aged 18–40 years recruited from a non-surgical outpatient spine clinic between March 2011 and October 2013 (n = 1037). Questionnaires were collected at baseline, 1-year, and 4-year follow-up. Disability was assessed using the Roland Morris Disability Questionnaire (RMDQ 0-100) and pain intensity using the Numeric Rating Scale (NRS 0–10). ’Mild-moderate pain’ was defined as NRS < 7 and ’severe pain’ as NRS ≥ 7. Likewise, ’mild-moderate disability’ was defined as RMDQ < 58.3, and ’severe disability’ was RMDQ ≥ 58.3. In the prognostic analysis, improvement in pain and disability over 4 years was defined as meeting both criteria: decrease of ≥ 2 on the NRS and of ≥ 20.8 on the RMDQ. Sixteen candidate prognostic factors were assessed by multivariate logistic regression.

Results

Among patients with information available at all three time points (n = 241), 54%/48% had persistent mild-moderate pain/disability, while only 7%/15% had persistent severe pain/disability. Of patients included in the multivariate prognostic analysis regarding improvement over 4 years (n = 498), 32% had improved in pain and disability after 4 years. Positive associations were found for pain intensity (OR 1.34 [95%CI: 1.17–1.54]), disability (OR 1.01 [1.00-1.02]), and regular employment or studying (OR 1.67 [1.06–2.64]), and negative associations for episode duration (OR 0.99 [0.99-1.00]) and risk of persistent pain (OR 0.58 [0.38–0.88]).

Conclusion

Patients with persistent LBP in secondary care had mostly mild-moderate pain and disability consistently at all three time points, with few having consistently severe symptoms over 4 years. Moreover, approximately half of the included patients improved in pain and disability. We found that pain intensity, disability, episode duration, regular employment or studying, and risk of persistent pain predicted a long-term improvement. However, the limited availability of complete follow-up data may affect generalisability.