bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous Determination of Six Components in Beagle Dog Plasma by UPLC-MS/MS and Its Application to a Comparative Pharmacokinetic Study of Three Different Yuanhu Zhitong Preparations
Authors: Wang Yang , Yin Zhaorui , Zhang Kai , Meng Qingfen , Guan Jianli , Fan Guanwei
Published: September 2022

This study has developed a sensitive, simple, and reliable ultrahigh performance liquid chromatography tandem mass spectrometry method for the simultaneous determination of corydaline, tetrahydropalmatine, tetrahydroberberine, tetrahydrocoptisine, byakangelicin, and byakangelicol in beagle dog plasma after oral administration of Yuanhu Zhitong (YHZT) oral liquid, dispersible tablet, and dropping pills. A one-step protein precipitation method was used with methanol-acetonitrile (50 : 50, v/v) for plasma sample pretreatment. Six analytes and one internal standard were separated on a Waters Acquity UPLC BEH C18 column (2.1 mm × 100 mm, 1.7 μm) by gradient elution with 0.1% formic acid-water and 0.1% formic acid-acetonitrile at a flow rate of 0.4 mL/min. Detection was conducted by multiple reaction monitoring mode in the positive ionization. The calibration curves showed good linearity (r > 0.9920). The lower limit of quantization ranged from 0.1 to 1 ng/mL. Moreover, the other results of the method validation were within the acceptable range. After oral administration, the pharmacokinetic characteristics of the three YHZT preparations were different. Compared with the two solid preparations, the absorption of the six analytes in oral liquid was more rapid. Moreover, the area under the plasma drug concentration-time curve and the maximum plasma concentration of tetrahydropalmatine (the main analgesic component of YHZT prescription) in the oral liquid group were higher than those in the other two groups. The results showed oral liquid can exert its efficacy quickly, while dispersible tablet and dropping pills exhibit relatively slow release pattern. The comparative pharmacokinetic study would be helpful to the clinical rational selection and application of YHZT preparations.
Experimental Study on Unsteady Radon Exhalation from the Overburden Layer of the Uranium Mill Tailings Pond under Rainfall
Authors: Wang Hong , Wang Wenhua , He Runcheng , Hong Changshou , Wang Jin , Li Xiangyang , Liu Yong
Published: September 2022

In order to find out radon reduction performance of the overburden layer on uranium mill tailings (UMTs) pond beach surface after rainfall, the rainfall simulation experiment of the overburden layer was carried out with the self-developed equipment. Based on the radon migration model of the overburden layer on the UMTs pond beach surface, the change rule of radon exhalation in four types of compactness of the overburden layer within 120 hours after rainfall was studied, and the corresponding moisture content was also analyzed. The results show that the radon concentration in the overburden layer of UMTs increases nonlinearly; the dynamic change in moisture content of the overburden layer on the beach surface leads to the unsteady radon exhalation. The variation of radon exhalation shows three stages: increase, linear decrease, and stability tendency. After rainfall, radon exhalation rate increases due to water vapor and there is free radon seepage in pores. With the decrease of free radon production rate, radon exhalation rate gradually decreases until it reaches stability again. When the thickness of the overburden layer reduces, the porosity decreases with the increase in compactness of the overburden layer. While the decrease in radon reduction is more obvious, the less time it takes for radon exhalation to vary from unstable to stable overburden after rainfall.
SEM‐Based Analysis of Carbon Emission Reduction Pathway Study during the Materialization Stage of Prefabricated Buildings: Evidence from Shenyang and Guiyang, China
Authors: Zhu Rui , Li Lihong
Published: September 2022

In recent years, in the process of promoting prefabricated buildings, problems such as waste of resources and energy have been present, which have seriously hindered the realization of carbon emission reduction benefits of prefabricated buildings. Especially during the materialization stage of prefabricated buildings which involves the most engineering activities and the most extensive sources of carbon emissions, it is urgent to further meet the low‐carbon development of the construction industry. This study takes the 4 substages of design and development, component production, transportation, and installation during the materialization stage as the point of penetration and identifies the carbon reduction impact pathways based on the 3E (Environment‐Economy‐Energy) system theory in 5 dimensions: government policy, management mode, technology level, economy input, and energy structure. The data are collected through the questionnaire survey, and structural equation modeling (SEM) is utilized to examine the hypothesis and impact dimensions of the study. The results confirm that the management mode has the strongest effects on carbon emission reduction, followed by government policy, economy input, and technology level, and the energy structure has the weakest effects. This study presents the key carbon reduction pathways during the materialization stage of prefabricated buildings and provides recommendations for different participants to optimize policy guidance, strengthen management supervision, accelerate technology research and development, increase economy input, and optimize energy structure, with a view to achieving low‐carbon governance capacity, management mode, technology system, capital, and energy utilization, and also enriches the theory in the field of prefabricated buildings carbon emission reduction, which can better achieve low‐carbon development of prefabricated buildings.
Successful Novel Treatment of Nonuremic Calciphylaxis with Sodium Thiosulfate and Iloprost: A Case Report
Authors: Wiltfang Lisa , Booken Nina , Schneider Stefan W.
Published: September 2022

Calciphylaxis is a rare and potentially life-threatening disease which occurs most frequently in end-stage renal disease. Here, we describe a 69-year-old male patient who presented to the clinic with extremely painful necrotic ulcers of the right lower extremity. His risk factors included hypertension, diabetes mellitus type II, steatosis hepatis, and chronic hepatitis B. Laboratory studies revealed no signs for uremia, hyperparathyroidism, and normal phosphorus as well as calcium levels. A diagnosis of nonuremic calciphylaxis was made in correlation with clinical and histological features. A novel therapeutic approach combining sodium thiosulfate and iloprost showed remarkable improvement of the wound-associated pain and healing of the ulcers within 3 months. Due to its high mortality rate, an early diagnosis and initiation of treatment are crucial to be beneficial for patient outcomes.
Fifteen Years after Sleeve Gastrectomy: Gastroscopies, Manometries, and 24-h pH-Metries in a Long-Term Follow-Up: A Multicenter Study
Authors: Felsenreich Daniel Moritz , Artemiou Evi , Wintersteller Lukas , Jedamzik Julia , Eichelter Jakob , Gensthaler Lisa , Bichler Christoph , Sperker Christoph , Beckerhinn Philipp , Kristo Ivan , Langer Felix Benedikt , Prager Gerhard
Published: September 2022

Introduction: Sleeve gastrectomy (SG) is the most common bariatric operation with over 340,000 procedures per year. There are only few studies presenting follow-up results >10 years in the literature today. The aim of this study was the objective evaluation of long-term outcomes of at least 15 years after SG in non-converted patients. Methods: This study (multicenter cross-sectional; university-hospital based) includes all non-converted patients with primary SG before December 2005 at participating bariatric centers. The following methods were used: gastroscopy, esophageal manometry, 24-h pH-metry, and Gastrointestinal Quality of Life Index (GIQLI). Results: After removing converted patients, patients with bariatric procedures before SG, and deceased patients from the cohort, 20 of 53 participants have met the inclusion criteria. Of this group, 55% are suffering from symptomatic gastroesophageal reflux disease (GERD); 45% are without GERD. Esophagitis, hiatal hernias, Barrett’s esophagus, and enlarged sleeves were found in 44%, 50%, 13%, and 69% of patients during gastroscopy. Mean lower esophageal sphincter pressure was normal at 20.2 ± 14.1 mm Hg during manometry. Reflux activity in 24 h, number of refluxes, and DeMeester score were increased at 12.9 ± 9.7%, 98.0 ± 80.8, and 55.3 ± 36.3 during 24-h pH-metry. Patients with GERD scored significantly lower in the GIQLI than patients without GERD: 107.6 ± 18.4 versus 127.6 ± 14.4 (p = 0.04). Discussion/Conclusion: Fifteen years after primary SG, objective testing has shown that GERD, esophagitis, and Barrett’s esophagus are major issues for these patients. Surveillance endoscopies at 5-year intervals in all SG patients and 3-year intervals in patients with Barrett’s esophagus are recommended.
Solitary Cardiac Metastasis from Colorectal Cancer: A Case Report
Authors: Numata Koji , Urata Nozomi , Nakayama Yuta , Ju Mihwa , Tanaka Ayano , Nakayama Hirotaka , Yamanaka Kazuki , Hatori Shinsuke , Matsubara Osamu , Rino Yasushi , Tani Kazuyuki
Published: September 2022

A 73-year-old woman with silent cardiac metastasis underwent high anterior resection for rectal cancer 3 years ago. Follow-up computed tomography showed a tumor in the right atrium. Partial vascular resection of the superior vena cava and right atrium was performed. Early postoperative recurrence occurred, and chemotherapy was unsuccessful. The patient died 7 months after surgery.
Effects of Coronary Artery Disease–Associated Variants on Vascular Smooth Muscle Cells
Authors: Solomon Charles U. , McVey David G. , Andreadi Catherine , Gong Peng , Turner Lenka , Stanczyk Paulina J. , Khemiri Sonja , Chamberlain Julie C. , Yang Wei , Webb Tom R. , Nelson Christopher P. , Samani Nilesh J. , Ye Shu
Published: September 2022

Background:

Genome-wide association studies have identified many genetic loci that are robustly associated with coronary artery disease (CAD). However, the underlying biological mechanisms are still unknown for most of these loci, hindering the progress to medical translation. Evidence suggests that the genetic influence on CAD susceptibility may act partly through vascular smooth muscle cells (VSMCs).

Methods:

We undertook genotyping, RNA sequencing, and cell behavior assays on a large bank of VSMCs (n>1499). Expression quantitative trait locus and splicing quantitative trait locus analyses were performed to identify genes with an expression that was influenced by CAD-associated variants. To identify candidate causal genes for CAD, we ascertained colocalizations of VSMC expression quantitative trait locus signals with CAD association signals by performing causal variants identification in associated regions analysis and the summary data–based mendelian randomization test. Druggability analysis was then performed on the candidate causal genes. CAD risk variants were tested for associations with VSMC proliferation, migration, and apoptosis. Collective effects of multiple CAD-associated variants on VSMC behavior were estimated by polygenic scores.

Results:

Approximately 60% of the known CAD-associated variants showed statistically significant expression quantitative trait locus or splicing quantitative trait locus effects in VSMCs. Colocalization analyses identified 84 genes with expression quantitative trait locus signals that significantly colocalized with CAD association signals, identifying them as candidate causal genes. Druggability analysis indicated that 38 of the candidate causal genes were druggable, and 13 had evidence of drug-gene interactions. Of the CAD-associated variants tested, 139 showed suggestive associations with VSMC proliferation, migration, or apoptosis. A polygenic score model explained up to 5.94% of variation in several VSMC behavior parameters, consistent with polygenic influences on VSMC behavior.

Conclusions:

This comprehensive analysis shows that a large percentage of CAD loci can modulate gene expression in VSMCs and influence VSMC behavior. Several candidate causal genes identified are likely to be druggable and thus represent potential therapeutic targets.
Exploring personalized structural connectomics for moderate to severe traumatic brain injury
Authors: Imms Phoebe , Clemente Adam , Deutscher Evelyn , Radwan Ahmed M. , Akhlaghi Hamed , Beech Paul , Wilson Peter H. , Irimia Andrei , Poudel Govinda , Domínguez Duque Juan F. , Caeyenberghs Karen
Published: September 2022

Graph theoretical analysis of the structural connectome has been employed successfully to characterize brain network alterations in patients with traumatic brain injury (TBI). However, heterogeneity in neuropathology is a well-known issue in the TBI population, such that group comparisons of patients against controls are confounded by within-group variability. Recently, novel single-subject profiling approaches have been developed to capture inter-patient heterogeneity. We present a personalized connectomics approach that examines structural brain alterations in five chronic patients with moderate to severe TBI who underwent anatomical and diffusion magnetic resonance imaging. We generated individualized profiles of lesion characteristics and network measures (including personalized graph metric GraphMe plots, and nodal and edge-based brain network alterations) and compared them against healthy reference cases (N = 12) to assess brain damage qualitatively and quantitatively at the individual level. Our findings revealed alterations of brain networks with high variability between patients. With validation and comparison to stratified, normative healthy control comparison cohorts, this approach could be used by clinicians to formulate a neuroscience-guided integrative rehabilitation program for TBI patients, and for designing personalized rehabilitation protocols based on their unique lesion load and connectome.
New Moroccan bee species of the tribe Osmiini (Hymenoptera: Apoidea: Megachilidae)
Authors: MÜLLER ANDREAS
Published: September 2022

The examination of undetermined material of Moroccan bees of the tribe Osmiini (Megachilidae) and several excursions to Morocco in the past fifteen years revealed the existence of numerous undescribed osmiine bee species, indicating that the Moroccan osmiine bee diversity is distinctly higher than the 148 species listed in a recent compilation. In the present publication, 14 of these new species are described: Hoplitis (Alcidamea) herrmanni spec. nov., Hoplitis (Anthocopa) clypeoincisa spec. nov., Hoplitis (Anthocopa) convolvuli spec. nov., Hoplitis (Anthocopa) prazi spec. nov., Hoplitis (Anthocopa) sedivyi spec. nov., Hoplitis (Anthocopa) sternocarinata spec. nov., Hoplitis (Anthocopa) widmeri spec. nov., Hoplitis (Hoplitis) maussi spec. nov., Hoplitis (Hoplitis) prosii spec. nov., Hoplitis (Hoplitis) weibeli spec. nov., Hoplitis (Tkalcua) sidiifnii spec. nov., Osmia (Nasutosmia) longipalpa spec. nov., Protosmia (Nanosmia) curviseta spec. nov. and Protosmia (Nanosmia) magna spec. nov.. Apart from H. prazi, which has a wide distribution ranging from Morocco eastwards to the Levant, and H. clypeoincisa, which has been found in northeastern Morocco and is expected to occur also in neighbouring Algeria, all other new species have been recorded only in southern Morocco and are possibly Moroccan endemics.
First records of Pochazia shantungensis (Chou & Lu, 1977) (Hemiptera: Fulgoromorpha: Ricaniidae) in Italy
Authors: STROIŃSKI ADAM , BALDERI MATTEO , MARRACCINI DANIELE , MAZZA GIUSEPPE
Published: September 2022

The invasive ricaniid species Pochazia shantungensis (Chou & Lu, 1977), an Asiatic pest in China and Korea, is reported for the first time in Italy. This is the fourth confirmed record from Europe after Turkey, France, and Germany. The list of the host plants recorded in Europe is given. Illustrations of male and female genital structures (external and internal) are also presented.
ortho2align: a sensitive approach for searching for orthologues of novel lncRNAs
Authors: Mylarshchikov Dmitry Evgenevich , Mironov Andrey Alexandrovich
Published: September 2022

Background

Many novel long noncoding RNAs have been discovered in recent years due to advances in high-throughput sequencing experiments. Finding orthologues of these novel lncRNAs might facilitate clarification of their functional role in living organisms. However, lncRNAs exhibit low sequence conservation, so specific methods for enhancing the signal-to-noise ratio were developed. Nevertheless, current methods such as transcriptomes comparison approaches or searches for conserved secondary structures are not applicable to novel, previously unannotated lncRNAs by design.

Results

We present ortho2align—a versatile sensitive synteny-based lncRNA orthologue search tool with statistical assessment of sequence conservation. This tool allows control of the specificity of the search process and optional annotation of found orthologues. ortho2align shows similar performance in terms of sensitivity and resource usage as the state-of-the-art method for aligning orthologous lncRNAs but also enables scientists to predict unannotated orthologous sequences for lncRNAs in question. Using ortho2align, we predicted orthologues of three distinct classes of novel human lncRNAs in six Vertebrata species to estimate their degree of conservation.

Conclusions

Being designed for the discovery of unannotated orthologues of novel lncRNAs in distant species, ortho2align is a versatile tool applicable to any genomic regions, especially weakly conserved ones. A small amount of input files makes ortho2align easy to use in orthology studies as a single tool or in bundle with other steps that researchers will consider sensible. ortho2align is available as an Anaconda package with its source code hosted at https://github.com/dmitrymyl/ortho2align.
Joint models for dynamic prediction in localised prostate cancer: a literature review
Authors: Parr Harry , Hall Emma , Porta Nuria
Published: September 2022

Background

Prostate cancer is a very prevalent disease in men. Patients are monitored regularly during and after treatment with repeated assessment of prostate-specific antigen (PSA) levels. Prognosis of localised prostate cancer is generally good after treatment, and the risk of having a recurrence is usually estimated based on factors measured at diagnosis. Incorporating PSA measurements over time in a dynamic prediction joint model enables updates of patients’ risk as new information becomes available. We review joint model strategies that have been applied to model time-dependent PSA trajectories to predict time-to-event outcomes in localised prostate cancer.

Methods

We identify articles that developed joint models for prediction of localised prostate cancer recurrence over the last two decades. We report, compare, and summarise the methodological approaches and applications that use joint modelling accounting for two processes: the longitudinal model (PSA), and the time-to-event process (clinical failure). The methods explored differ in how they specify the association between these two processes.

Results

Twelve relevant articles were identified. A range of methodological frameworks were found, and we describe in detail shared-parameter joint models (9 of 12, 75%) and joint latent class models (3 of 12, 25%). Within each framework, these articles presented model development, estimation of dynamic predictions and model validations.

Conclusions

Each framework has its unique principles with corresponding advantages and differing interpretations. Regardless of the framework used, dynamic prediction models enable real-time prediction of individual patient prognosis. They utilise all available longitudinal information, in addition to baseline prognostic risk factors, and are superior to traditional baseline-only prediction models.
Orbital apex syndrome secondary to apical periodontitis of a tooth: a case report
Authors: Xiang Wei , Wei Hongchun , Xu Luyao , Liang Zhigang
Published: September 2022

Background

Orbital apex syndrome (OAS) is a rare disease with a noticeable mortality rate. Although its etiology has been repeatedly assessed, few reports have concentrated on odontogenic infection. We presented a rare case of OAS secondary to apical periodontitis.

Case presentation

A 61-year-old male was admitted to our hospital for a 3-day history of left orbital and head pain, along with diplopia for 1-day. He also had toothache symptoms before his admission. Due to the atypical early symptoms of orbital apex and cranial nerve injury, no timely and effective diagnosis and treatment were initially provided. However, as the disease progressed and complications occurred, we timely adjusted the diagnosis and successfully controlled the infection. During the one-year follow-up, no recurrence of inflammation was observed; nevertheless, the ptosis and ophthalmoplegia persisted.

Conclusions

OAS is a rare, while severe complication of odontogenic infection. This case had various symptoms and nerve injury in the orbital apical area. When disease is atypical in its early stages, treatment is easily overlooked. Early detection and suspicion of orbital apex-related complications should be heightened.
The presence and co-incidence of geriatric syndromes in older patients with mild-moderate Lewy body dementia
Authors: Gan Jinghuan , Chen Zhichao , Liu Shuai , Shi Zhihong , Liu Yiming , Wang Xiao-Dan , Liu Chunyan , Ji Yong
Published: September 2022

Introduction

Geriatric symptoms are common in dementia cases, while few studies have focused on these symptoms in Lewy body dementia (LBD). The purpose of this study is to investigate the distributions of Apolipoprotein E (APOE) ε4 and geriatric symptoms, and explore their associaitons in Dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD).

Methods

A retrospective study with 185 mild-moderate probable DLB (n = 93) and PDD (n = 92) patients was assigned. Demographic and clinical characteristics, neuropsychological assessments, and APOE genotypes were recorded. Description, correlation and logistic regression models were used to analyze the presence of geriatric symptom complaints and their associations with APOE ε4.

Results

DLB patients displayed more frequency of fluctuating cognition, visual hallucination, rapid eye movement sleep behavior disorder, delusion, depression, anxiety, apathy, and loss of appetite, whereas the PDD cases had constipation, fear of falling, and insomnia more frequently. The APOE ε4 allele was more common in DLB than PDD (29.9% vs. 7.0%, p < 0.001), and the patients with DLB + APOE ε4 (+) were presented more delusions (p = 0.005) and apathy (p = 0.007) than patients with PDD + APOE ε4 (+). We also found that the APOE ε4 allele was significantly associated with hyperhidrosis (OR = 3.472, 95%CI: 1.082–11.144, p = 0.036) and depression (OR = 3.002, 95%CI: 1.079–8.353, p = 0.035) in DLB patients, while there were no significant associations between APOE ε4 allele and the age at visit, the age at onset, scores of MDS-UPDRS III, H&Y stage, ADL, MMSE, MOCA and NPI, as well as the presences of fluctuating cognition, VH, parkinsonism and RBD in both groups.

Conclusion

The presence and co-incidence of geriatric symptoms are common in patients with mild-moderate LBD. The presence of APOE ε4 allele is associated with hyperhidrosis and depression, but not global cognition, activitives of daily life, motor function and other neuropsychitric symptoms in DLB. These findings improve the awareness of geriatric symptoms, and contribute to the healthcare management of mild-moderate DLB and PDD.
Prevalence and associated risk factors for anxiety and depression in infertile couples of ART treatment: a cross-sectional study
Authors: Zhang Li , Shao Hongfang , Huo Mian , Chen Jie , Tao Minfang , Liu Zhangshun
Published: September 2022

Background

Infertility now is a public health concern and is associated with increased psychological distress.

Methods

We enrolled 1247 infertile couples and assessed their anxiety and depression status before and during assisted reproductive technology (ART) treatment using the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS). The Chi-square or fisher’s exact test was used to analyze the prevalence of anxiety and depression in infertile couples. Multivariate logistical regression was performed to analyze the risk factors for anxiety and depression.

Results

The prevalence of anxiety was 13.5% and 8.7% (p < 0.05), and that of depression was 9.4% and 7.9% (p = 0.2) in female and male partners, respectively. Female SAS and SDS scores were positively associated with male SAS and SDS scores, respectively (r = 0.52 andr = 0.50, respectively, bothp < 0.0001), and were positively associated with their own SDS and SAS scores, respectively (r = 0.63 andr = 0.62, respectively, bothp < 0.0001). Their own depression or partners’ anxiety was associated with the anxiety, and their own anxiety or partners’ depression was associated with the depression in infertile couples. No children, unemployment, and low education level were also associated with female anxiety. SAS and SDS scores were significantly decreased during ART treatment.

Conclusions

Females were more vulnerable to having anxiety than males in infertile couples. Anxiety and depression in infertile couples could interact, therefore, anxiety and depression would be simultaneously counseled, and their partners also should be given supportive psychotherapy.

Trial registration

It was an observational study and had no health care interventions on participants. So it was not registrated.
Medium-term oncological outcomes of totally laparoscopic colectomy with intracorporeal anastomosis for right-sided and left-sided colon cancer: propensity score matching analysis
Authors: Hamamoto Hiroki , Suzuki Yusuke , Takano Yoshiaki , Kuramoto Toru , Ishii Masatsugu , Osumi Wataru , Masubuchi Shinsuke , Tanaka Keitaro , Uchiyama Kazuhisa
Published: September 2022

Background

This retrospective study aimed to compare long-term oncological outcomes between laparoscopic-assisted colectomy (LAC) with extracorporeal anastomosis (EA) and totally laparoscopic colectomy (TLC) with intracorporeal anastomosis (IA) for colon cancers, including right- and left-sided colon cancers.

Methods

Patients with stage I–III colon cancers who underwent elective laparoscopic colectomy between January 2013 and December 2017 were analyzed retrospectively. Patients converted from laparoscopic to open surgery and R1/R2 resection were excluded. Propensity score matching (PSM) analysis (1:1) was performed to overcome patient selection bias.

Results

A total of 388 patients were reviewed. After PSM, 83 patients in the EA group and 83 patients in the IA group were compared. Median follow-up was 56.5 months in the EA group and 55.5 months in the IA group. Estimated 3-year overall survival (OS) did not differ significantly between the EA group (86.6%; 95% confidence interval (CI), 77.4–92.4%) and IA group (84.8%; 95%CI, 75.0–91.1%; P = 0.68). Estimated 3-year disease-free survival (DFS) likewise did not differ significantly between the EA group (76.4%; 95%CI, 65.9–84.4%) and IA group (81.0%; 95%CI, 70.1–88.2%; P = 0.12).

Conclusion

TLC with IA was comparable to LAC with EA in terms of 3-year OS and DFS. TLC with IA thus appears to offer an oncologically feasible procedure.
Anti-Indigenous bias of medical school applicants: a cross-sectional study
Authors: Roach Pamela , Hernandez Santanna , Carbert Amanda , Jalil Rabiya , Panaccione Remo , Ruzycki Shannon M.
Published: September 2022

Background

Structural and interpersonal anti-Indigenous racism is prevalent in Canadian healthcare. The Truth and Reconciliation Commission calls on medical schools to address anti-Indigenous bias in students. We measured the prevalence of interpersonal anti-Indigenous bias among medical school applicants to understand how the medical school selection process selects for or against students with high levels of bias.

Methods

All applicants to a single university in the 2020–2021 admissions cycle were invited to participate. Explicit anti-Indigenous bias was measured using two sliding scale thermometers. The first asked how participants felt about Indigenous people (from 0, indicating ‘cold/unfavourable’ to 100, indicating ‘warm/favourable’) and the second asked whether participants preferred white (scored 100) or Indigenous people (scored 0). Participants then completed an implicit association test examining preferences for European or Indigenous faces (negative time latencies suggest preference for European faces). Explicit and implicit anti-Indigenous biases were compared by applicant demographics (including gender and racial identity), application status (offered an interview, offered admission, accepted a position), and compared to undergraduate medical and mathematics students.

Results

There were 595 applicant respondents (32.4% response rate, 64.2% cisgender women, 55.3% white). Applicants felt warmly toward Indigenous people (median 96 (IQR 80–100)), had no explicit preference for white or Indigenous people (median 50 (IQR 37–55), and had mild implicit preference for European faces (− 0.22 ms (IQR -0.54, 0.08 ms)). There were demographic differences associated with measures of explicit and implicit bias. Applicants who were offered admission had warmer feelings toward Indigenous people and greater preference for Indigenous people compared to those were not successful.

Conclusions

Medical school applicants did not have strong interpersonal explicit and implicit anti-Indigenous biases. Outlier participants with strong biases were not offered interviews or admission to medical school.
Impact of the use of illicit and licit substances and anxiety disorders on the academic performance of medical students: a pilot study
Authors: Ferreira Pedro Marques , Alves Rauni Jandé Roama , Zantut-Wittmann Denise Engelbrecht
Published: September 2022

Background

Medical students have a considerable prevalence of anxiety and substance use disorders. Our aim was to assess the presence of anxiety disorders and the use of alcohol and licit and illicit substances, and their influence on the academic performance of medical students.

Methods

This is a cross-sectional, non-experimental pilot study, with quantitative analyses, in which 67 medical students at the Federal University of Rondonópolis, Mato Grosso, Brazil (UFR), were evaluated through the application of non-invasive anxiety assessment instruments, screening for involvement with tobacco, alcohol and other substances, related to school performance coefficient, between June 2019 and March 2020.

Results

Worse academic performance was associated with frequent use of tobacco and its derivatives (p = 0.0022), marijuana (p = 0.0020), hypnotics and sedatives (p = 0.0138). Also, the performance was negatively correlated with the use of tobacco (p = 0.0004), alcoholic beverages (p = 0.0261), cannabis (p = 0.0075), sedatives (p = 0.0116) and trait anxiety (p = 0.0036). Greater trait anxiety intensity was associated with previous use of tobacco (p = 0.0276), marijuana (p = 0.0466), amphetamines/ecstasy (p = 0.0151), and hypnotics/sedatives (p = 0.0103). State anxiety was positively correlated with heavy alcohol use (p = 0.0434). Higher state anxiety intensity was related to needing intervention due to the use of amphetamines/ecstasy (p = 0.00379). Students from the intermediate classes of the course (3rd and 4th years) had a higher frequency and intensity of use of tobacco and its derivatives (p = 0.0133), amphetamines or ecstasy (p = 0.0006), and inhalants (p = 0.0256).

Conclusions

Worse academic performance in medical students was correlated with licit and illicit substances use and anxiety disorders. Mid-course students had a higher frequency and intensity of substance use.
Three novel leaderless bacteriocins have antimicrobial activity against gram-positive bacteria to serve as promising food biopreservative
Authors: Zhang Xiaofeng , Xin Nie , Zhu Zhaolu , Li Xudong , Dai Dadong , Pan Chunmei , Peng Donghai , Sun Ming
Published: September 2022

Background

Due to the detrimental effects of chemical preservatives, there has been an increasing demand for safer, healthier and natural bio-preservatives. Bacteriocins have attracted increasing interest because of their potential as natural bio-preservatives.

Results

We screened a large number of Bacillus thuringiensis strains and isolated one strain (B. thuringiensis P86) with antimicrobial activity against several foodborne pathogens. Three novel leaderless bacteriocins, including thucin A1, thucin A2 and thucin A3, were purified and identified from the culture supernatant of B. thuringiensis P86, whose molecular masses were 5552.02, 5578.07 and 5609.06 Da, respectively. Thucin A1 was then selected as a representative to be tested, and it exhibited potent inhibitory activity against all tested gram-positive bacteria. More importantly, thucin A1 showed stronger antimicrobial activity than nisin A against two important foodborne pathogens Bacillus cereus and Listeria monocytogenes. In addition, thucin A1 exhibited strong acid–base adaptability (pH 2–11), high endurance to heat, good stability to trypsin and pepsin, no hemolysis activity and cytotoxicity, and could effectively inhibit or eliminate Bacillus cereus and Listeria monocytogenes in skim milk.

Conclusions

Our findings indicate that these novel leaderless bacteriocins are potentially promising food biopreservatives.
Micropeptide MIAC inhibits the tumor progression by interacting with AQP2 and inhibiting EREG/EGFR signaling in renal cell carcinoma
Authors: Li Mengwei , Liu Guangxiang , Jin Xinrong , Guo Hongqian , Setrerrahmane Sarra , Xu Xindi , Li Tiantian , Lin Yunfei , Xu Hanmei
Published: September 2022

Background

Although, micropeptides encoded by non-coding RNA have been shown to have an important role in a variety of tumors processes, there have been no reports on micropeptide in renal cell carcinoma (RCC). Based on the micropeptide MIAC (micropeptide inhibiting actin cytoskeleton) discovered and named in the previous work, this study screened its tumor spectrum, and explored its mechanism of action and potential diagnosis and treatment value in the occurrence and development of renal carcinoma.

Methods

The clinical significance of MIAC in RCC was explored by bioinformatics analysis through high-throughput RNA-seq data from 530 patients with kidney renal clear cell carcinoma (KIRC) in the TCGA database, and the detection of clinical samples of 70 cases of kidney cancer. In vitro and in vivo experiments to determine the role of MIAC in renal carcinoma cell growth and metastasis; High-throughput transcriptomics, western blotting, immunoprecipitation, molecular docking, affinity experiments, and Streptavidin pulldown experiments identify MIAC direct binding protein and key regulatory pathways.

Results

The analysis of 600 renal carcinoma samples from different sources revealed that the expression level of MIAC is significantly decreased, and corelated with the prognosis and clinical stage of tumors in patients with renal carcinoma. Overexpression of MIAC in renal carcinoma cells can significantly inhibit the proliferation and migration ability, promote apoptosis of renal carcinoma cells, and affect the distribution of cells at various stages. After knocking down MIAC, the trend is reversed. In vivo experiments have found that MIAC overexpression inhibit the growth and metastasis of RCC, while the synthetized MIAC peptides can significantly inhibit the occurrence and development of RCC in vitro and in vivo. Further mechanistic studies have demonstrated that MIAC directly bind to AQP2 protein, inhibit EREG/EGFR expression and activate downstream pathways PI3K/AKT and MAPK to achieve anti-tumor effects.

Conclusions

This study revealed for the first time the tumor suppressor potential of the lncRNA-encoded micropeptide MIAC in RCC, which inhibits the activation of the EREG/EGFR signaling pathway by direct binding to AQP2 protein, thereby inhibiting renal carcinoma progression and metastasis. This result emphasizes that the micropeptide MIAC can provide a new strategy for the diagnosis and treatment of RCC.
Mucopolysaccharidoses and the blood–brain barrier
Authors: Sahin Onur , Thompson Hannah P. , Goodman Grant W. , Li Jun , Urayama Akihiko
Published: September 2022

Mucopolysaccharidoses comprise a set of genetic diseases marked by an enzymatic dysfunction in the degradation of glycosaminoglycans in lysosomes. There are eight clinically distinct types of mucopolysaccharidosis, some with various subtypes, based on which lysosomal enzyme is deficient and symptom severity. Patients with mucopolysaccharidosis can present with a variety of symptoms, including cognitive dysfunction, hepatosplenomegaly, skeletal abnormalities, and cardiopulmonary issues. Additionally, the onset and severity of symptoms can vary depending on the specific disorder, with symptoms typically arising during early childhood. While there is currently no cure for mucopolysaccharidosis, there are clinically approved therapies for the management of clinical symptoms, such as enzyme replacement therapy. Enzyme replacement therapy is typically administered intravenously, which allows for the systemic delivery of the deficient enzymes to peripheral organ sites. However, crossing the blood–brain barrier (BBB) to ameliorate the neurological symptoms of mucopolysaccharidosis continues to remain a challenge for these large macromolecules. In this review, we discuss the transport mechanisms for the delivery of lysosomal enzymes across the BBB. Additionally, we discuss the several therapeutic approaches, both preclinical and clinical, for the treatment of mucopolysaccharidoses.
Stimulation of protein synthesis by optogenetic and chemical induction of excitatory synaptic plasticity in hippocampal somatostatin interneurons
Authors: Honoré Ève , Belo do Nascimento Inês , Laplante Isabel , Lacaille Jean-Claude
Published: September 2022

Somatostatin-expressing interneurons (SOM-INs) are a major subpopulation of GABAergic cells in CA1 hippocampus that receive excitation from pyramidal cells (PCs) and provide feedback control of synaptic inputs onto PC dendrites. Excitatory synapses from PCs onto SOM-INs (PC-SOM synapses) exhibit long-term potentiation (LTP) mediated by type 1a metabotropic glutamate receptors (mGluR1a). LTP at PC-SOM synapses translates in lasting regulation of metaplasticity of entorhinal and CA3 synaptic inputs on PCs and contributes to hippocampus-dependent learning. A persistent form of PC-SOM synapse LTP lasting hours is prevented by blockers of transcription and translation, and a more transient form of PC-SOM synapse LTP lasting tens of minutes requires mTORC1-signaling, suggesting an involvement of protein synthesis. However, the role of protein synthesis in these forms of plasticity has not been directly demonstrated. Here we use the SUrface SEnsing of Translation (SUnSET) assay of protein synthesis to directly show that the induction protocols for both forms of LTP at PC-SOM synapses stimulate protein synthesis in SOM-INs. Moreover, protein synthesis stimulated by persistent LTP induction was prevented in mice with a SOM-IN conditional knock-out of Raptor, an essential component of mTORC1, indicating a critical role of mTORC1 in the control of translation in PC-SOM synapse plasticity. Moreover, protein synthesis induced by both forms of LTP may share common mechanisms as transient LTP induction occluded further stimulation of protein synthesis by persistent LTP induction. Our findings highlight a crucial role of protein synthesis and its control by mTORC1 in SOM-INs that is important for hippocampus-dependent memory function.
Elucidating the diversity of malignant mesenchymal states in glioblastoma by integrative analysis
Authors: Chanoch-Myers Rony , Wider Adi , Suva Mario L. , Tirosh Itay
Published: September 2022

Background

Multiple glioblastoma studies have described a mesenchymal (MES) state, with each study defining the MES program by distinct sets of genes and highlighting distinct functional associations, including both immune activation and suppression. These variable descriptions complicate our understanding of the MES state and its implications. Here, we hypothesize that there is a range of glioma MES states, possibly reflecting distinct prior states in which a MES program can be induced, and/or distinct mechanisms that induce the MES states in those cells.

Methods

We integrated multiple published single-cell and bulk RNA sequencing datasets and MES signatures to define a core MES program that recurs across studies, as well as multiple function-specific MES signatures that vary across MES cells. We then examined the co-occurrence of these signatures and their associations with genetic and microenvironmental features.

Results

Based on co-occurrence of MES signatures, we found three main variants of MES states: hypoxia-related (MES-Hyp), astrocyte-related (MES-Ast), and an intermediate state. Notably, the MES states are differentially associated with genetic and microenvironmental features. MES-Hyp is preferentially associated with NF1 deletion, overall macrophage abundance, a high macrophage/microglia ratio, and M2-related macrophages, consistent with previous studies that associated MES with immune suppression. In contrast, MES-Ast is associated with T cell abundance and cytotoxicity, consistent with immune activation through expression of MHC-I/II.

Conclusions

Diverse MES states occur in glioblastoma. These states share a subset of core genes but differ primarily in their association with hypoxia vs. astrocytic expression programs, and with immune suppression vs. activation, respectively.
The association between dietary insulin index and load with mental health
Authors: Darand Mina , Amirinejad Ali , Salehi-Abargouei Amin , Davies Ian G. , Mirzaei Masoud , Mazidi Mohsen , Khayyatzadeh Sayyed Saeid
Published: September 2022

Background

Depression, anxiety, and stress are common mental problems. The aim of this cross-sectional study was to investigate the association between two indexes that measure postprandial insulin response to different food, dietary insulin index (DII) and insulin load (DIL), with psychological disorders.

Method

Participants (n = 10,000) aged 20–69 were randomly selected from 200 clusters in Yazd from the recruitment phase of the Yazd Health Study. The dietary intake of participants was collected by a reliable and validated food frequency questionnaire (FFQ) consisting of 178 food items. DII and DIL were calculated from the FFQ data using previously published reference values. To assess psychological disorders an Iranian validated short version of a self-reported questionnaire (Depression Anxiety Stress Scales 21 [DASS21]) was used.

Results

No significant association was observed between DIL and DII with odds of depression or anxiety using crude or adjusted models. However, individuals in the highest quartiles of DIL had the lowest odds of stress (OR: 0.69; 95% CI 0.48–1.01, P-trend = 0.047). This association remained significant after adjustment for potential confounders in model II including marital status, smoking, education, job status, salt intake, and multi-vitamin supplement use (OR: 0.38; 95% CI 0.16–0.91, P-trend = 0.039) and the third and final model which is further adjusted for BMI (OR: 0.39; 95% CI 0.16–0.91, P-trend = 0.041).

Conclusion

Overall, consumption of foods with higher DII as well as DIL were associated with lower stress scores; however, no significant relationship was observed between DII or DIL with respective depression or anxiety scores.
Religious affiliation seldom seems to influence hiring or competence ratings of job applicants: studies conducted in Sweden and in the USA
Authors: Hallin Nathalie , Västfjäll Daniel , Andersson Gerhard
Published: September 2022

Background

Religion is an important ingroup characteristic for many people. For different reasons, people with different religious affiliations might prefer members of their religious outgroup. Previous studies have investigated perceptions of and behaviour toward religious ingroup and outgroup members in various contexts. The four studies presented here investigated whether competence and likeability ratings differ depending on the target’s and participant’s religious affiliations in a recruitment context. Two studies were conducted in Sweden, while the other two were conducted in the USA.

Methods

Participants in 4 studies rated a Christian, Muslim or atheist job applicant and a control applicant on 4 competence and 3 likeability items on 7-point Likert scales. The difference in ratings between the target applicant and control applicant was used to measure perceived competence and likeability of the target applicant. In the two latter studies, one in Sweden and one in the USA, participants also chose to hire either the target or the control applicant.

Results

Overall, participants in three studies rated control applicants as more likeable than target applicants. In the two US studies, targets were also rated as less competent than control applicants. Christian participants in the two US studies rated the Christian applicant as more likeable than both other targets. In the second US study, atheist participants rated Christians as less likeable than both other targets. In one of the Swedish studies, atheist participants rated the atheist applicant as more likeable than both other targets. The only significant difference in competence ratings between targets was made by Christian Swedes, who rated Muslim applicants as less competent than Christian applicants. The only significant difference in hiring decisions was that Swedish atheist participants hired Christians less often than they hired control applicants.

Conclusion

Together, the results suggest that job applicants are sometimes viewed as more likeable if they belong to a religious ingroup rather than a religious outgroup, but that this only rarely translate to significant differences in competence ratings or hiring decisions.
TP53 mutations in functional corticotroph tumors are linked to invasion and worse clinical outcome
Authors: Perez-Rivas Luis Gustavo , Simon Julia , Albani Adriana , Tang Sicheng , Roeber Sigrun , Assié Guillaume , Deutschbein Timo , Fassnacht Martin , Gadelha Monica R. , Hermus Ad R. , Stalla Günter K. , Tichomirowa Maria A. , Rotermund Roman , Flitsch Jörg , Buchfelder Michael , Nasi-Kordhishti Isabella , Honegger Jürgen , Thorsteinsdottir Jun , Saeger Wolfgang , Herms Jochen , Reincke Martin , Theodoropoulou Marily
Published: September 2022

Corticotroph macroadenomas are rare but difficult to manage intracranial neoplasms. Mutations in the two Cushing’s disease mutational hotspots USP8 and USP48 are less frequent in corticotroph macroadenomas and invasive tumors. There is evidence that TP53 mutations are not as rare as previously thought in these tumors. The aim of this study was to determine the prevalence of TP53 mutations in corticotroph tumors, with emphasis on macroadenomas, and their possible association with clinical and tumor characteristics. To this end, the entire TP53 coding region was sequenced in 86 functional corticotroph tumors (61 USP8 wild type; 66 macroadenomas) and the clinical characteristics of patients with TP53 mutant tumors were compared with TP53/USP8 wild type and USP8 mutant tumors. We found pathogenic TP53 variants in 9 corticotroph tumors (all macroadenomas and USP8 wild type). TP53 mutant tumors represented 14% of all functional corticotroph macroadenomas and 24% of all invasive tumors, were significantly larger and invasive, and had higher Ki67 indices and Knosp grades compared to wild type tumors. Patients with TP53 mutant tumors had undergone more therapeutic interventions, including radiation and bilateral adrenalectomy. In conclusion, pathogenic TP53 variants are more frequent than expected, representing a relevant amount of functional corticotroph macroadenomas and invasive tumors. TP53 mutations associated with more aggressive tumor features and difficult to manage disease.