bluuebunny/crossref_metadata_2025 huggingface dataset:
Opioid-free total intravenous anesthesia for thyroid and parathyroid surgery: Protocol for a randomized, double-blind, controlled trial
Authors: Wang Dan , Long Yu-qin , Sun Yan , Zhu Ya-juan , Feng Xiao-mei , Liu Hong , Ji Fu-hai , Peng Ke
Published: August 2022

Background

Opioid-free anesthesia (OFA) may improve postoperative outcomes by reducing opioid-related adverse effects. This study aims to evaluate the effects of OFA on postoperative nausea and vomiting (PONV), postoperative pain, and 30-day outcomes after thyroid and parathyroid surgery.

Methods

This two-center, randomized, double-blind, controlled trial will include 400 adult patients scheduled for thyroid and parathyroid surgery. Patients will be randomly assigned, 1:1 and stratified by sex and site, to an OFA group (esketamine, lidocaine, and dexmedetomidine) or a control group (opioid-based anesthesia with sufentanil). All patients will receive propofol-based total intravenous anesthesia and PONV prophylaxis with dexamethasone and ondansetron. The primary outcome is the incidence of PONV (defined as experiencing any event of nausea, retching, or vomiting) during the first 48 h postoperatively. The secondary outcomes include the severity of PONV, antiemetic rescue therapy, pain scores at rest and while coughing, need for rescue analgesia, perioperative adverse effects related to anesthetics or analgesics (hypotension, bradycardia, hypertension, tachycardia, desaturation, dizziness, headache, hallucination, and nightmare), time to extubation, length of post-anesthesia care unit stay, length of postoperative hospital stay, patient satisfaction, and a composite of 30-day major adverse events (myocardial infarction, cardiac arrest, cerebrovascular accident, coma, acute renal failure, pulmonary embolism, sepsis, septic shock, deep neck space infection, reintubation, reoperation, blood transfusion, failure to wean off ventilator, and death). Analyses will be performed in the modified intention-to-treat population.

Discussion

We hypothesize that our OFA regimen reduces PONV after thyroid and parathyroid surgery. We will also investigate whether OFA leads to improvements in postoperative pain and major adverse events. Our results will offer evidence for optimizing anesthesia regimens in patients who undergo thyroid and parathyroid surgical procedures.

Clinical trial registration

http://www.chictr.org.cn, identifier: ChiCTR2200059656.
Is ectopic Cushing’s syndrome underdiagnosed in patients with small cell lung cancer?
Authors: Piasecka Marta , Larsson Martin , Papakokkinou Eleni , Olsson Lena , Ragnarsson Oskar
Published: August 2022

Introduction

Ectopic Cushing’s syndrome (ECS) is an uncommon disorder. Recently, however, a larger proportion of patients with endogenous Cushing’s syndrome (CS) had ECS than has previously been reported.

Objective

The aim of this study was to determine whether ECS is an underdiagnosed disorder in patients with small-cell lung cancer (SCLC).

Materials and methods

Medical records from consecutive patients diagnosed with SCLC at our hospital between 2013 and 2019 were reviewed (N = 213; mean age 69.5 ± 9 years; range, 36–89 years). The probability of having ECS was evaluated by review of biochemical and clinical features, including presence of recent onset diabetes mellitus, therapy resistant hypertension and/or spontaneous hypokalaemia.

Results

Of 213 identified patients with SCLC, one (0.5%) patient had confirmed ECS, two (1%) patients had probable ECS, and twenty-three (11%) patients had possibly ECS. Patients with SCLC and possibly or probable ECS exhibited a significantly shorter survival than patients only with SCLC (8 vs. 14 months, respectively).

Conclusions

Our findings indicate that ECS is underdiagnosed in patients with SCLC. Given the serious consequences of untreated ECS, the low detection rate highlights the need to improve endocrine work-up of patients with SCLC who present with biochemical and clinical features associated with ECS. Prospective studies are needed to establish a reliable assessment of the incidence of ECS and to optimise early detection strategies.
COVID-19 and the potential of Janus family kinase (JAK) pathway inhibition: A novel treatment strategy
Authors: Khaledi Mansoor , Sameni Fatemeh , Yahyazade Sheida , Radandish Maedeh , Owlia Parviz , Bagheri Nader , Afkhami Hamed , Mahjoor Mohamad , Esmaelpour Zahra , Kohansal Maryam , Aghaei Farzad
Published: August 2022

Recent evidence proposed that the severity of the coronavirus disease 2019 (COVID-19) in patients is a consequence of cytokine storm, characterized by increased IL-1β, IL-6, IL-18, TNF-α, and IFN-γ. Hence, managing the cytokine storm by drugs has been suggested for the treatment of patients with severe COVID-19. Several of the proinflammatory cytokines involved in the pathogenesis of COVID-19 infection recruit a distinct intracellular signaling pathway mediated by JAKs. Consequently, JAK inhibitors, including baricitinib, pacritinib, ruxolitinib, and tofacitinib, may represent an effective therapeutic strategy for controlling the JAK to treat COVID-19. This study indicates the mechanism of cytokine storm and JAK/STAT pathway in COVID-19 as well as the medications used for JAK/STAT inhibitors.
Pathologists Overseas: A volunteer-based model for building sustainable, high-quality pathology and laboratory medicine services in low- and middle-income countries
Authors: Glynn Emily H. , Nelson Ann Marie , Tesfazghi Merih , Harb Roa , Amukele Timothy
Published: August 2022

For thirty years Pathologists Overseas (PO) has worked in low- and middle-income countries (LMICs) to provide affordable, sustainable, and high-quality pathology and laboratory medicine (PALM) services through strategic partnerships and the efforts of our large volunteer network. We address low quality diagnostic services by targeting the 3 pillars of PALM quality: human resources, systems, and quality and accreditation. To improve human resource capacity, PO and our partnering organizations provide virtual continuing education to pathologists and laboratory professionals in these countries. To improve systems, we provide laboratory information system installation and implementation support. Lastly, to improve quality and help laboratories progress toward accreditation, we support an external quality assurance program for laboratories in LMICs. As a relatively small organization, PO demonstrates that a network of dedicated volunteers, in partnership with corporations and professional organizations, can initiate sustainable change in the quality of PALM services in LMICs by focusing efforts on the core components of laboratory quality.
Comparison of clinical safety and efficacy of dexmedetomidine, remifentanil, and propofol in patients who cannot tolerate non-invasive mechanical ventilation: A prospective, randomized, cohort study
Authors: Altınkaya Çavuş Mine , Gökbulut Bektaş Serife , Turan Sema
Published: August 2022

Background and objectives

Non-invasive ventilation (NIV) is used in intensive care units (ICUs) to treat of respiratory failure. Sedation and analgesia are effective and safe for improving compliance in patients intolerant to NIV. Our study aimed to evaluate the effects of dexmedetomidine, remifentanil, and propofol on the clinical outcomes in NIV intolerant patients.

Methods

This prospective randomized cohort study was conducted in a tertiary ICU, between December 2018 and December 2019. We divided a total of 120 patients into five groups (DEXL, DEXH, REML, REMH, PRO). IBM SPSS Statistics 20 (IBM Corporation, Armonk, New York, USA) was used to conduct the statistical analyses.

Results

The DEXL, DEXH, REML, and REMH groups consisted of 23 patients each while the PRO group consisted of 28 patients. Seventy-five patients (62.5%) became tolerant of NIV after starting the drugs. The NIV time, IMV time, ICU LOS, hospital LOS, intubation rate, side effects, and mortality were significantly different among the five groups (P = 0.05). In the groups that were given dexmedetomidine (DEXL, and DEXH), NIV failure, mortality, ICU LOS, and hospital LOS were lower than in the other groups.

Conclusion

In this prospective study, we compared the results of three drugs (propofol, dexmedetomidine, and remifentanil) in patients with NIV intolerance. The use of sedation increased NIV success in patients with NIV intolerance. NIV failure, mortality, ICU LOS, IMV time, and hospital LOS were found to be lower with dexmedetomidine.
Alzheimer’s Disease Polygenic Risk Score Is Not Associated With Cognitive Decline Among Older Adults With Type 2 Diabetes
Authors: Manzali Sigalit B. , Yu Eric , Ravona-Springer Ramit , Livny Abigail , Golan Sapir , Ouyang Yuxia , Lesman-Segev Orit , Liu Lang , Ganmore Ithamar , Alkelai Anna , Gan-Or Ziv , Lin Hung-Mo , Heymann Anthony , Schnaider Beeri Michal , Greenbaum Lior
Published: August 2022

Objectives

Multiple risk loci for late-onset Alzheimer’s disease (LOAD) have been identified. Type 2 diabetes (T2D) is a risk factor for cognitive decline, dementia and Alzheimer’s disease (AD). We investigated the association of polygenic risk score (PRS) for LOAD with overall cognitive functioning and longitudinal decline, among older adults with T2D.

Methods

The study included 1046 Jewish participants from the Israel Diabetes and Cognitive Decline (IDCD) study, aged ≥ 65 years, diagnosed with T2D, and cognitively normal at baseline. The PRS included variants from 26 LOAD associated loci (at genome-wide significance level), and was calculated with and without APOE. Outcome measures, assessed in 18 months intervals, were global cognition and the specific domains of episodic memory, attention/working memory, executive functions, and language/semantic categorization. Random coefficient models were used for analysis, adjusting for demographic variables, T2D-related characteristics, and cardiovascular factors. Additionally, in a subsample of 202 individuals, we analyzed the association of PRS with the volumes of total gray matter, frontal lobe, hippocampus, amygdala, and white matter hyperintensities. Last, the association of PRS with amyloid beta (Aβ) burden was examined in 44 participants who underwent an 18F-flutemetamol PET scan.

Results

The PRS was not significantly associated with overall functioning or decline in global cognition or any of the specific cognitive domains. Similarly, following correction for multiple testing, there was no association with Aβ burden and other brain imaging phenotypes.

Conclusion

Our results suggest that the cumulative effect of LOAD susceptibility loci is not associated with a greater rate of cognitive decline in older adults with T2D, and other pathways may underlie this link.
Exploring brain changes of impulse control disorders in Parkinson's disease: An ALE study
Authors: Gu Lihua , Shu Hao , Wang Yanjuan , Xu Hui
Published: August 2022

Background

Previous neuroimaging studies reported inconsistent results for comparison between Parkinson's disease (PD) with impulse control disorder (PD-ICD) and without ICD (PD-no ICD).

Methods

A search was performed in databases (PubMed and Web of Science) to identify studies published before May 2022. An anatomic likelihood estimation (ALE) method study was made for neuroimaging studies in PD-ICD.

Results

The study included 20 studies (including 341 PD-ICD and 437 PD-no ICD). PD-ICD patients showed significant cortical thinning in the right inferior frontal gyrus (IFG), the right middle frontal gyrus (MFG), the left superior frontal gyrus (SFG), the right precentral gyrus (PCG) and the left cingulate gyrus (CG), compared to PD-no ICD patients. The ALE study showed reduced resting-state brain activation in the right IFG, the right PCG, the left insula and the right transverse temporal gyrus (TTG) in PD-ICD, compared to PD-no ICD patients. In addition, PD-ICD showed increased resting-state brain activation in the right caudate, the bilateral insula and the left orbital gyrus (OG), compared to PD-no ICD patients. The study indicated reduced task-related brain activation in the right caudate, the right MFG, the right lentiform nucleus (LN) and the right precuneus (PCUN) in PD-ICD, compared to PD-no ICD patients. The study showed increased task-related brain activation in the left inferior parietal lobule (IPL), the right medial frontal gyrus, the right caudate and the right PCG in PD-ICD, compared to PD-no ICD patients.

Conclusions

The present ALE analysis has confirmed that brain changes in frontal, temporal and basal ganglia regions are among the most frequently reported regions in PD-ICD. Deficits in these regions could play a role in diagnosis of PD-ICD.
Amygdala response predicts clinical symptom reduction in patients with borderline personality disorder: A pilot fMRI study
Authors: Geurts Dirk E. M. , Van den Heuvel Thom J. , Huys Quentin J. M. , Verkes Robbert J. , Cools Roshan
Published: August 2022

Borderline personality disorder (BPD) is a prevalent, devastating, and heterogeneous psychiatric disorder. Treatment success is highly variable within this patient group. A cognitive neuroscientific approach to BPD might contribute to precision psychiatry by identifying neurocognitive factors that predict who will benefit from a specific treatment. Here, we build on observations that BPD is accompanied by the enhanced impact of the aversive effect on behavior and abnormal neural signaling in the amygdala. We assessed whether BPD is accompanied by abnormal aversive regulation of instrumental behavior and associated neural signaling, in a manner that is predictive of symptom reduction after therapy. We tested a clinical sample of 15 female patients with BPD, awaiting dialectical behavior therapy (DBT), and 16 matched healthy controls using fMRI and an aversive Pavlovian-to-instrumental transfer (PIT) task that assesses how instrumental behaviors are influenced by aversive Pavlovian stimuli. Patients were assessed 1 year after the start of DBT to quantify changes in BPD symptom severity. At baseline, behavioral aversive PIT and associated neural signaling did not differ between groups. However, the BOLD signal in the amygdala measured during aversive PIT was associated with symptom reduction at 1-year follow-up: higher PIT-related aversive amygdala signaling before treatment was associated with reduced clinical improvement at follow-up. Thus, within the evaluated group of BPD patients, the BOLD signal in the amygdala before treatment was related to clinical symptom reduction 1 year after the start of treatment. The results suggest that less PIT-related responsiveness of the amygdala increases the chances of treatment success. We note that the relatively small sample size is a limitation of this study and that replication is warranted.
Methamphetamine signals transcription of IL1β and TNFα in a reactive oxygen species-dependent manner and interacts with HIV-1 Tat to decrease antioxidant defense mechanisms
Authors: Basova Liana V. , Vien Whitney , Bortell Nikki , Najera Julia A. , Marcondes Maria Cecilia Garibaldi
Published: August 2022

Methamphetamine (Meth) abuse is a common HIV co-morbidity that is linked to aggravated Central Nervous System (CNS) inflammation, which accentuates HIV- associated neurological disorders, triggered both directly or indirectly by the drug. We used the well-established human innate immune macrophage cell line system (THP1) to demonstrate that Reactive Oxygen Species (ROS) immediately induced by Meth play a role in the increased transcription of inflammatory genes, in interaction with HIV-1 Tat peptide. Meth and Tat, alone and together, affect early events of transcriptional activity, as indicated by changes in RNA polymerase (RNAPol) recruitment patterns throughout the genome, via ROS-dependent and -independent mechanisms. IL1β (IL1β) and TNF α (TNFα), two genes with defining roles in the inflammatory response, were both activated in a ROS-dependent manner. We found that this effect occurred via the activation of the activator protein 1 (AP-1) comprising cFOS and cJUN transcription factors and regulated by the SRC kinase. HIV-1 Tat, which was also able to induce the production of ROS, did not further impact the effects of ROS in the context of Meth, but promoted gene activity independently from ROS, via additional transcription factors. For instance, HIV-1 Tat increased NFkB activation and activated gene clusters regulated by Tata box binding peptide, ING4 and IRF2. Importantly, HIV-1 Tat decreased the expression of anti-oxidant genes, where its suppression of the detoxifying machinery may contribute to the aggravation of oxidative stress induced by ROS in the context of Meth. Our results provide evidence of effects of Meth via ROS and interactions with HIV Tat that promote the transcription of inflammatory genes such as IL1β and TNFα.
A comprehensive mouse brain acetylome-the cellular-specific distribution of acetylated brain proteins
Authors: Ji Yuhua , Chen Zixin , Cen Ziqi , Ye Yuting , Li Shuyuan , Lu Xiaoshuang , Shao Qian , Wang Donghao , Ji Juling , Ji Qiuhong
Published: August 2022

Nε-lysine acetylation is a reversible posttranslational modification (PTM) involved in multiple physiological functions. Genetic and animal studies have documented the critical roles of protein acetylation in brain development, functions, and various neurological disorders. However, the underlying cellular and molecular mechanism are still partially understood. Here, we profiled and characterized the mouse brain acetylome and investigated the cellular distribution of acetylated brain proteins. We identified 1,818 acetylated proteins, including 5,196 acetylation modification sites, using a modified workflow comprising filter-aided sample preparation (FSAP), acetylated peptides enrichment, and MS analysis without pre- or post-fraction. Bioinformatics analysis indicated these acetylated mouse brain proteins were mainly located in the myelin sheath, mitochondrial inner membrane, and synapse, as well as their involvement in multiple neurological disorders. Manual annotation revealed that a set of brain-specific proteins were acetylation-modified. The acetylation of three brain-specific proteins was verified, including neurofilament light polypeptide (NEFL), 2’,3’-cyclic-nucleotide 3’-phosphodiesterase (CNP), and neuromodulin (GAP43). Further immunofluorescence staining illustrated that acetylated proteins were mainly distributed in the nuclei of cortex neurons and axons of hippocampal neurons, sparsely distributed in the nuclei of microglia and astrocytes, and the lack of distribution in both cytoplasm and nuclei of cerebrovascular endothelial cells. Together, this study provided a comprehensive mouse brain acetylome and illustrated the cellular-specific distribution of acetylated proteins in the mouse brain. These data will contribute to understanding and deciphering the molecular and cellular mechanisms of protein acetylation in brain development and neurological disorders. Besides, we proposed some problems that need to be solved in future brain acetylome research.
Structural magnetic resonance imaging findings and histopathological correlations in motor neuron diseases—A systematic review and meta-analysis
Authors: Zejlon Charlotte , Nakhostin Dominik , Winklhofer Sebastian , Pangalu Athina , Kulcsar Zsolt , Lewandowski Sebastian , Finnsson Johannes , Piehl Fredrik , Ingre Caroline , Granberg Tobias , Ineichen Benjamin Victor
Published: August 2022

Objectives

The lack of systematic evidence on neuroimaging findings in motor neuron diseases (MND) hampers the diagnostic utility of magnetic resonance imaging (MRI). Thus, we aimed at performing a systematic review and meta-analysis of MRI features in MND including their histopathological correlation.

Methods

In a comprehensive literature search, out of 5941 unique publications, 223 records assessing brain and spinal cord MRI findings in MND were eligible for a qualitative synthesis. 21 records were included in a random effect model meta-analysis.

Results

Our meta-analysis shows that both T2-hyperintensities along the corticospinal tracts (CST) and motor cortex T2*-hypointensitites, also called “motor band sign”, are more prevalent in ALS patients compared to controls [OR 2.21 (95%-CI: 1.40–3.49) and 10.85 (95%-CI: 3.74–31.44), respectively]. These two imaging findings correlate to focal axonal degeneration/myelin pallor or glial iron deposition on histopathology, respectively. Additionally, certain clinical MND phenotypes such as amyotrophic lateral sclerosis (ALS) seem to present with distinct CNS atrophy patterns.

Conclusions

Although CST T2-hyperintensities and the “motor band sign” are non-specific imaging features, they can be leveraged for diagnostic workup of suspected MND cases, together with certain brain atrophy patterns. Collectively, this study provides high-grade evidence for the usefulness of MRI in the diagnostic workup of suspected MND cases.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42020182682.
The impact of cerebellar transcranial direct current stimulation (tDCS) on sensorimotor and inter-sensory temporal recalibration
Authors: Schmitter Christina V. , Straube Benjamin
Published: August 2022

The characteristic temporal relationship between actions and their sensory outcomes allows us to distinguish self- from externally generated sensory events. However, the complex sensory environment can cause transient delays between action and outcome calling for flexible recalibration of predicted sensorimotor timing. Since the neural underpinnings of this process are largely unknown this study investigated the involvement of the cerebellum by means of cerebellar transcranial direct current stimulation (ctDCS). While receiving anodal, cathodal, dual-hemisphere or sham ctDCS, in an adaptation phase, participants were exposed to constant delays of 150 ms between actively or passively generated button presses and visual sensory outcomes. Recalibration in the same (visual outcome) and in another sensory modality (auditory outcome) was assessed in a subsequent test phase during which variable delays between button press and visual or auditory outcome had to be detected. Results indicated that temporal recalibration occurred in audition after anodal ctDCS while it was absent in vision. As the adaptation modality was visual, effects in audition suggest that recalibration occurred on a supra-modal level. In active conditions, anodal ctDCS improved sensorimotor recalibration at the delay level closest to the adaptation delay, suggesting a precise cerebellar-dependent temporal recalibration mechanism. In passive conditions, the facilitation of inter-sensory recalibration by anodal ctDCS was overall stronger and tuned to larger delays. These findings point to a role of the cerebellum in supra-modal temporal recalibration across sensorimotor and perceptual domains, but the differential manifestation of the effect across delay levels in active and passive conditions points to differences in the underlying mechanisms depending on the availability of action-based predictions. Furthermore, these results suggest that anodal ctDCS can be a promising tool for facilitating effects of temporal recalibration in sensorimotor and inter-sensory contexts.
Explainable artificial intelligence based on feature optimization for age at onset prediction of spinocerebellar ataxia type 3
Authors: Ru Danlei , Li Jinchen , Xie Ouyi , Peng Linliu , Jiang Hong , Qiu Rong
Published: August 2022

Existing treatments can only delay the progression of spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) after onset, so the prediction of the age at onset (AAO) can facilitate early intervention and follow-up to improve treatment efficacy. The objective of this study was to develop an explainable artificial intelligence (XAI) based on feature optimization to provide an interpretable and more accurate AAO prediction. A total of 1,008 affected SCA3/MJD subjects from mainland China were analyzed. The expanded cytosine-adenine-guanine (CAG) trinucleotide repeats of 10 polyQ-related genes were genotyped and included in related models as potential AAO modifiers. The performance of 4 feature optimization methods and 10 machine learning (ML) algorithms were compared, followed by building the XAI based on the SHapley Additive exPlanations (SHAP). The model constructed with an artificial neural network (ANN) and feature optimization of Crossing-Correlation-StepSVM performed best and achieved a coefficient of determination (R2) of 0.653 and mean absolute error (MAE), root mean square error (RMSE), and median absolute error (MedianAE) of 4.544, 6.090, and 3.236 years, respectively. The XAI explained the predicted results, which suggests that the factors affecting the AAO were complex and associated with gene interactions. An XAI based on feature optimization can improve the accuracy of AAO prediction and provide interpretable and personalized prediction.
Structure-function models of temporal, spatial, and spectral characteristics of non-invasive whole brain functional imaging
Authors: Raj Ashish , Verma Parul , Nagarajan Srikantan
Published: August 2022

We review recent advances in using mathematical models of the relationship between the brain structure and function that capture features of brain dynamics. We argue the need for models that can jointly capture temporal, spatial, and spectral features of brain functional activity. We present recent work on spectral graph theory based models that can accurately capture spectral as well as spatial patterns across multiple frequencies in MEG reconstructions.
La protein regulates protein expression by binding with the mRNAs of target genes and participates the pathological process of ovarian cancer
Authors: Huang Xuan , Zhu Jialei , Li Yueyan , Yu Yang , Tang Jing
Published: August 2022

Research on the mechanism and new targets of ovarian cancer is of great significance to reduce the high mortality and drug resistance of ovarian cancer. Human La protein has been found to be highly expressed in a variety of malignant tumors and plays a role in tumorigenesis and development through its RNA-binding function. However, its role and mechanism in ovarian cancer are not completely clear. The present study showed that La protein was highly expressed in serum and tissues of patients with ovarian cancer by ELISA and immunohistochemistry, and the high expression of La protein was associated with the increased degree of malignancy and poor prognosis by searching the KM plotter database. Interference of the La gene resulted in a significant decrease in the proliferation, migration, and invasion of ovarian cancer cells with growth block in the G1 phase and increasing apoptosis. By RNA binding protein immunoprecipitation, transcriptome sequencing, and proteomics, 14 downstream target genes were screened. The La protein might affect the protein expression of these 14 genes by binding with the mRNAs. Therefore, it played a role in the pathological process of ovarian cancer.
Cost-Effectiveness of Pembrolizumab for the treatment of Non–Small-Cell lung cancer: A systematic review
Authors: Zhang Chuan , Zhang Jiaxu , Tan Jing , Tian Panwen , Li Weimin
Published: August 2022

Introduction

Pembrolizumab, an immune checkpoint inhibitor for treating non-small cell lung cancer (NSCLC), can impose a high financial burden. Several studies have explored the cost-effectiveness of this expensive agent. We conducted a systematic review and pooled analysis to evaluate the quality of the existing pharmacoeconomic studies on pembrolizumab strategies for NSCLC treatment as well as to conclude the cost-effectiveness of such strategies.

Methods

English and Chinese databases were searched to collect health economic studies on pembrolizumab therapies (monotherapy or a combination with chemotherapy) compared with chemotherapy for the treatment of NSCLC patients. The reporting quality, modeling methods, and results of incremental cost-effectiveness analysis of the included literature were descriptively analyzed.

Results

A total of 24 studies, 3 in Chinese and 21 in English, were selected. All reports satisfy a median of 31 out of 40 reporting quality assessment items based on a quality checklist for pharmacoeconomic evaluations. 12 studies used the Markov model and 11 used the partitioned survival model. A common problem identified in the modeling methods was the insufficient justification of the choices of model structure and data inputs. Pembrolizumab was found to be cost-effective in the United States and Switzerland, but not in China, France, the UK, or Singapore.

Conclusion

The current cost-effectiveness studies on pembrolizumab for the treatment of NSCLC are of moderate quality, and the relevant decision-analytic modeling methods have much scope for improvement. The cost-effectiveness of pembrolizumab strategies for NSCLC varies across countries, warranting the need to pay more attention to the methodologies of pharmacoeconomic research in order to produce correct outcomes in terms of cost-effectiveness for different countries.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021250480
Solitary extramedullary plasmacytoma in the lung misdiagnosed as lung cancer: A case report and literature review
Authors: Wang Jingjing , Yang Xiaoyun , Liu Xiaomei , He Tao , Liu Bin , Yang Lei , Yuan Fei , Li Jing
Published: August 2022

Background

Extramedullary plasmacytoma (EMP) is an extremely rare kind of soft tissue plasma cell neoplasm without bone marrow involvement or other systemic characteristics of multiple myeloma. Primary pulmonary plasmacytoma (PPP), with no specific clinical manifestations, is an exceedingly rare type of EMP. Because of its complexity, PPP is often difficult to diagnose. Computed tomography-guided percutaneous core needle biopsy (CT-guided PCNB) has been shown to have high sensitivity, specificity and accuracy for characterization of pulmonary lesion, particularly if malignancy is suspected. Here we presented a rare case of PPP diagnosed with CT-guided PCNB.

Case presentation

A 78-year-old female smoker who visited our outpatient clinic for a mass in the left lower lobe of the lung. Pathological based on CT-guided PCNB yielded a PPP with no lymph node or other distant metastasis.

Conclusions

Extramedullary plasmacytoma should be considered in the differential diagnosis of a pulmonary mass.
Case Report: A rare case of primary hepatic Castleman’s disease mimicking a liver tumor
Authors: Chen Hong , Pang Xiaoxi , Li Jie , Xu Baixuan , Liu Yachao
Published: August 2022

Castleman’s disease (CD) is a primary lymphoproliferative disorder of the lymph nodes with rare extra-nodal primary affection. Solid organ involvement is rare, and isolated liver involvement is extremely rare. Here we presented a case of a 59-year-old woman with a hepatic lesion accidentally found by ultrasound. The MRI result indicated primary liver malignancy or liver metastases. 18F-FDG PET/CT could not exclude hepatic malignant tumor due to its high metabolism. Finally, the hepatic CD was confirmed by postoperative pathology.
A preoperative model based on gadobenate-enhanced MRI for predicting microvascular invasion in hepatocellular carcinomas (≤ 5 cm)
Authors: Zhang Sisi , Huo Lei , Zhang Juan , Feng Yayuan , Liu Yiping , Wu Yuxian , Jia Ningyang , Liu Wanmin
Published: August 2022

Purpose

The present study aimed to develop and validate a preoperative model based on gadobenate-enhanced magnetic resonance imaging (MRI) for predicting microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC) size of ≤5 cm. In order to provide preoperative guidance for clinicians to optimize treatment options.

Methods

164 patients with pathologically confirmed HCC and preoperative gadobenate-enhanced MRI from July 2016 to December 2020 were retrospectively included. Univariate and multivariate logistic regression (forward LR) analyses were used to determine the predictors of MVI and the model was established. Four-fold cross validation was used to verify the model, which was visualized by nomograms. The predictive performance of the model was evaluated based on discrimination, calibration, and clinical utility.

Results

Elevated alpha-fetoprotein (HR 1.849, 95% CI: 1.193, 2.867, P=0.006), atypical enhancement pattern (HR 3.441, 95% CI: 1.523, 7.772, P=0.003), peritumoral hypointensity on HBP (HR 7.822, 95% CI: 3.317, 18.445, P<0.001), and HBP hypointensity (HR 3.258, 95% CI: 1.381, 7.687, P=0.007) were independent risk factors to MVI and constituted the HBP model. The mean area under the curve (AUC), sensitivity, specificity, and accuracy values for the HBP model were as follows: 0.830 (95% CI: 0.784, 0.876), 0.71, 0.78, 0.81 in training set; 0.826 (95% CI:0.765, 0.887), 0.8, 0.7, 0.79 in test set. The decision curve analysis (DCA) curve showed that the HBP model achieved great clinical benefits.

Conclusion

In conclusion, the HBP imaging features of Gd-BOPTA-enhanced MRI play an important role in predicting MVI for HCC. A preoperative model, mainly based on HBP imaging features of gadobenate-enhanced MRI, was able to excellently predict the MVI for HCC size of ≤5cm. The model may help clinicians preoperatively assess the risk of MVI in HCC patients so as to guide clinicians to optimize treatment options.
Case report: First case report of an Emirati child with a novel gene variant causing aromatic L-amino acid decarboxylase deficiency
Authors: Babiker Mohamed O. E. , Kurian Manju A. , Suleiman Jehan
Published: August 2022

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare, neurometabolic disorder resulting from biallelic mutations in the dopa decarboxylase (DDC) gene. This is the first reported case of AADC deficiency in the United Arab Emirates (UAE) and describes an Emirati male patient who presented in the first few months of life with a severe phenotype of global hypotonia, developmental delay and oculogyric crisis. Following whole exome sequencing, a novel homozygous mutation in the DDC gene (c.1144G>T, p.Val382Phe) was reported and the patient underwent further testing, after which a diagnosis of AADC deficiency was confirmed. This mutation has not been previously described, but the clinical phenotype and corresponding biochemical profile confirmed that it is a pathogenic variant. The patient is currently managed at a tertiary referral center in the UAE and is treated in accordance with published guidance on AADC deficiency, including the recommended medical therapy combined with multidisciplinary care from a team of specialists. Some symptomatic improvements have been reported but at 5 years of age the patient continues to exhibit profound developmental delay, oculogyric crisis and is prone to recurrent respiratory infections. In order to improve outcomes for patients with AADC deficiency in the Middle Eastern region, there is an urgent need to raise the index of clinical suspicion, particularly among primary care physicians, pediatricians, and pediatric neurologists, and to improve access to diagnostic testing. This is particularly relevant at the current time, given the ongoing development of potentially disease-modifying gene therapy for AADC deficiency.
Transcatheter interventions in patients with a Fontan circulation: Current practice and future developments
Authors: Jalal Zakaria , Gewillig Marc , Boudjemline Younes , Guérin Patrice , Pilati Mara , Butera Gianfranco , Malekzadeh-Milani Sophie , Avesani Martina , Thambo Jean-Benoit
Published: August 2022

The Fontan operation represents the last of multiple steps that are offered a wide range of congenital cardiac lesions with a single ventricle (SV) physiology. Nowadays this surgical program consists of a total cavopulmonary connection (TCPC), by anastomosing systemic veins to the pulmonary arteries (PAs), excluding the right-sided circulation from the heart. As a result of imaging, surgical, percutaneous, and critical care improvements, survival in this population has steadily increased. However, the Fontan physiology chronically increases systemic venous pressure causing systemic venous congestion and decreased cardiac output, exposing patients to the failure of the Fontan circulation (FC), which is associated with a wide variety of clinical complications such as liver disease, cyanosis, thromboembolism, protein-losing enteropathy (PLE), plastic bronchitis (PB), and renal dysfunction, ultimately resulting in an increased risk of exercise intolerance, arrhythmias, and premature death. The pathophysiology of the failing Fontan is complex and multifactorial; i.e., caused by the single ventricle dysfunction (diastolic/systolic failure, arrhythmias, AV valve regurgitation, etc.) or caused by the specific circulation (conduits, pulmonary vessels, etc.). The treatment is still challenging and may include multiple options and tools. Among the possible options, today, interventional catheterization is a reliable option, through which different procedures can target various failing elements of the FC. In this review, we aim to provide an overview of indications, techniques, and results of transcatheter options to treat cavopulmonary stenosis, collaterals, impaired lymphatic drainage, and the management of the fenestration, as well as to explore the recent advancements and clinical applications of transcatheter cavopulmonary connections, percutaneous valvular treatments, and to discuss the future perspectives of percutaneous therapies in the Fontan population.
Effect of zinc versus vitamin A supplementation on pediatric patients with community-acquired pneumonia
Authors: Saied Aya , El Borolossy Radwa Maher , Ramzy Mourad Alfy , Sabri Nagwa A.
Published: August 2022

Background: Community-acquired pneumonia (CAP) is one of the most common infectious diseases affecting the respiratory tract and is responsible for a high mortality rate in children less than 5 years of age. The mortality rate due to CAP is much higher in low/middle-income countries than in high-income countries due to malnutrition and different micronutrient deficiencies that weaken the immune system.

Aim: The aim of this study was to compare the effects of zinc and vitamin A, as two elements of micronutrient agents, on the recovery rate of children suffering from CAP aged from 6 months to 5 years. The length of hospital stays was also investigated.

Method: A comparative, randomized, open-label, controlled, interventional study was carried out among children less than 5 years of age in the pediatric intensive care unit (PICU) diagnosed with CAP who were randomly divided into three groups. In addition to the standard therapy, group 1 was given zinc, group 2 was given vitamin A, and group 3 was the control group, given the standard therapy only. We compared the three groups in terms of recovery rate and hospital stay.

Result: The duration of hospitalization following zinc and vitamin A supplementation was reduced by an average of 3.21 days (95% CI: 5.01–1.41, p = 0.01) and 2.43 days (95% CI: 4.29–0.57, p = 0.01), respectively, compared to the control group. In addition, the two groups of vitamin A and zinc supplementation were associated with a shorter duration of pneumonic effusion (p < 0.001) in comparison to the control group. Additionally, there was no significant difference between the effects of zinc and vitamin A when compared to each other in terms of duration of hospital stay and pneumatic effusion.

Conclusion: The administration of zinc or vitamin A supplementation proved to be useful as an add-on therapy in community-acquired pneumonia, where it reduced the length of hospital stay and the duration of pneumonic effusion in pneumonic children less than 5 years of age.
The role of in vitro testing in pharmacovigilance for ß-lactam-induced serum sickness-like reaction: A pilot study
Authors: Elzagallaai Abdelbaset A. , Abuzgaia Awatif M. , Del Pozzo-Magaña Blanca R. , Loubani Eman , Rieder Michael J.
Published: August 2022

Background: Current pharmacovigilance (PV) methods for detection of adverse drug reactions (ADRs) fail to capture rare immune-mediated drug hypersensitivity reactions (DHRs) due to their scarcity and the lack of clear diagnostic criteria. Drug-induced serum sickness-like reactions (SSLRs) are rare type of DHRs that occur in susceptible patients 1–3 weeks after exposure to the culprit drug with ß-lactam antibiotics being the most associated drugs. The diagnosis of drug induced SSLR is difficult due to the lack of safe and reliable diagnostic tests for identifying the culprit drug. The lymphocyte toxicity assay (LTA) is an in vitro test used as a diagnostic tool for drug hypersensitivity reactions (DHRs).

Objective: To evaluate the role of the LTA test for diagnosing and capturing SSLR due to ß-lactam antibiotics in a cohort of patients.

Methods: Patients were recruited from patients referred to the Drug Hypersensitivity Clinic at Clinic at London Health Science Centre with suspicion of drug allergy. Twenty patients (10 males and 10 females) were selected to be tested to confirm diagnosis. Demographic data was collected form the patents and blood samples were withdrawn from all patients and from 20 healthy controls. The LTA test was performed on all subjects and data is expressed as percentage increase in cell death compared to control (vehicle without the drug).

Results: In the result of LTA tests performed on samples from the selected 20 patients. There was a significant (p < 0.05) concentration-dependent increase in cell death in cells isolated from patients as compared to cells from healthy controls when incubated with the drug in the presence of phenobarbitone-induced rat liver microsomes.

Conclusion: Giving its safety and good predictive value the LTA test has very strong potential to be a useful diagnostic tool for ß-lactam-induced SSLR. The test procedure is relatively simple and not overly costly. Further studies including other drug classes are needed to evaluate the utility of the LTA test for SSLR due to other drugs.
Antidepressant-like activity, active components and related mechanism of Hemerocallis citrina Baroni extracts
Authors: Liu Jinghong , Ye Tian , Yang Shuaiyong , Zhong Xiaohong , He Wei , Xu Mengtao , Fang Jinpeng , Deng Miao , Xu Ning , Zeng Jianguo , Qing Zhixing
Published: August 2022

Hemerocallis citrina Baroni [Asphodelaceae], which is traditional herbal medicine, has been widely used for treating depressive disorders in Eastern-Asia countries. However, the active compounds and corresponding mechanism of anti-depression are not yet completely clarified. In this study, the anti-depressive activities of six H. citrina extracts were primarily evaluated. The results showed that the water extract of H. citrina flowers (HCW) displays significant anti-depressive activity. A total of 32 metabolites were identified from HCW by high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS) and nuclear magnetic resonance (NMR). And then, the anti-depressive activity of the high-level compound (rutin) in HCW was also estimated. The results indicated that rutin displayed significant anti-depressive activity and was one of the main active ingredients. Finally, the anti-depressive mechanisms of HCW and rutin were investigated based on the intestinal microorganisms. The results showed that HCW and rutin increase the diversity and richness of the intestinal flora and regulate the specific intestinal microorganisms such as Bacteroides and Desulfovibrio genera in depressed mice. This work marks the first comprehensive study of the active components, anti-depressive activities and corresponding mechanisms of different H. citrina extracts, which provide a potential possibility for developing new antidepressants.
Comprehensive insights into the function and molecular and pharmacological regulation of neuron-derived orphan receptor 1, an orphan receptor
Authors: Hong Hongxiang , Su Jianbin , Huang Chao , Lu Xu , Cui Zhiming
Published: August 2022

Neuron-derived orphan receptor 1 (NOR1), also called nuclear receptor subfamily 4 group A member 3 (NR4A3), is a nuclear receptor belonging to the NR4A family. Since no endogenous ligand has been identified to date, NOR1 is also referred to as an orphan receptor. NOR1 is expressed in a variety of cells and tissues, including neurons, vascular smooth muscle cells, T lymphocytes, dendritic cells, tumor cells, heart, liver, and pancreas. Because NOR1 was first identified in apoptotic neurons, it is functionally associated with the regulation of cell migration and the growth of neuronal synapses. In-depth studies have shown that NOR1 can be edited by the immediate early gene and functions as a transcription factor. NOR1 has been shown to be rapidly induced by a number of stimulants including growth factors, fatty acids, and neurotransmitters. Elevated NOR1 levels may be involved in a number of pathophysiological processes. These include regulation of cellular apoptosis and regeneration, neuron formation, contextual fearing memory, inflammation, vascular smooth muscle proliferation, insulin secretion, and tumor development, whereby NOR1 mediates the pathogenesis of numerous diseases such as cerebral ischemia, depression, post-traumatic stress disorder, atherosclerosis, abdominal aortic aneurysm, cardiac hypertrophy, diabetes, osteoarthritis, rheumatoid arthritis, and cancer. However, to date, comprehensive insights into the function of NOR1 are not available in sources published online. In this review, we provide a brief overview of the function and molecular and pharmacological regulation of NOR1 in various pathological or physiological conditions to advance the development of NOR1 as a novel target for disease treatment.
High-order vortex harmonics generation by bi-circular Laguerre-Gaussian laser fields with relativistic plasmas
Authors: Xie Duan , Yin Yan , Yu Tongpu , Zhang Hao , Zhou Hongyu
Published: August 2022

Vortex beams with ultra-high brilliance can greatly enrich the light and matter interaction process and even shed light on the unexpected information in relativistic nonlinear optics. Thus, we propose a scheme for relativistic intense vortex harmonic radiation by use of bi-circular Laguerre–Gaussian lasers irradiating relativistic plasmas. Three-dimensional particle-in-cell simulation results show that the emitted harmonics own controllable spin and orbital angular momentum simultaneously, which can be attributed to the vortex mirror model and the related conservation laws. Meanwhile, the conversion efficiency of harmonic generation can be tuned through adjusting the intensity ratio of the two driving field components.
Automatic quantifying and monitoring follow-ups for implantable collamer lens implantation using AS-OCT images
Authors: Sun Yiming , Li Jinhao , Xu Peifang , Chen Pengjie , Wang Yaqi , Hu Shaodan , Jia Gangyong , Wang Shuai , Ye Juan
Published: August 2022

Purpose: To develop a deep learning method to automatically monitor the implantable collamer lens (ICL) position and quantify subtle alterations in the anterior chamber using anterior segment optical coherence tomography (AS-OCT) images for high myopia patients with ICL implantation.

Methods: In this study, 798 AS-OCT images of 203 patients undergoing ICL implantation at our eye center from April 2017 to June 2021 were involved. A deep learning system was developed to first isolate the corneoscleral, ICL, and lens, and then quantify clinical important parameters in AS-OCT images (central corneal thickness, anterior chamber depth, and lens vault).

Results: The deep learning system was able to accurately isolate the corneoscleral, ICL, and lens with the Dice coefficient ranging from 0.911 to 0.960, and all the F1 scores >0.900. The relative error between automated measurements and the ground truth for 95% (188 images out of 198) of LVs was within 10%. Intraclass correlation coefficients (ICCs) of the machine-ground truth measurements ranged from 0.928 to 0.995. The deep learning method also showed better repeatability than human graders.

Conclusion: The deep learning method provides reliable detection and quantification of AS-OCT scans for postoperative ICL implantation, which can simplify and optimize the management of clinical outcomes of ICL implantations. Also, this is a step towards an objective measurement of the postoperative vault, making the data more comparable and repeatable to each other.