bluuebunny/crossref_metadata_2025 huggingface dataset:
The prevalence of gastrointestinal symptoms and cobalamin deficiency in patients with chronic urticaria
Authors: Abadeh Armin , Herman Sari M. , Abdalian Rupert
Published: February 2023

Background

There is a paucity of studies reporting the presence of systemic symptoms and micronutrient deficiency in patients with chronic urticaria, and these data are lacking in a Canadian population.

Objective

To report the prevalence of gastrointestinal symptoms and vitamin B12 (cobalamin) deficiency in a Canadian patient population diagnosed with chronic urticaria.

Methods

A retrospective chart review of 100 adult patients with chronic urticaria was conducted. Demographic characteristics, medications, presence of gastrointestinal symptoms, and laboratory findings were abstracted from electronic medical records.

Results

Seventy percent of patients with chronic urticaria reported experiencing gastrointestinal symptoms. The most common symptom identified was gastroesophageal reflux (42%). Vitamin B12 (cobalamin) deficiency, defined as serum vitamin B12 level ≤ 250 pmol/L, was identified in 31.7% of the patients. Among those patients with urticaria and vitamin B12, 68% reported gastrointestinal symptoms.

Conclusions

This is the first study to provide data on the high prevalence of gastrointestinal symptoms and vitamin B12 (cobalamin) deficiency in a Canadian population diagnosed with chronic urticaria. Early recognition and management of systemic symptoms and micronutrient deficiency may lead to a more comprehensive approach to management of these patients.

Trial registrationNot applicable
Diffusion tensor imaging discriminates focal cortical dysplasia from normal brain parenchyma and differentiates between focal cortical dysplasia types
Authors: Gennari Antonio Giulio , Cserpan Dorottya , Stefanos-Yakoub Ilona , Kottke Raimund , O’Gorman Tuura Ruth , Ramantani Georgia
Published: February 2023

Objectives

Although diffusion tensor imaging (DTI) may facilitate the identification of cytoarchitectural changes associated with focal cortical dysplasia (FCD), the predominant aetiology of paediatric structural epilepsy, its potential has thus far remained unexplored in this population. Here, we investigated whether DTI indices can differentiate FCD from contralateral brain parenchyma (CBP) and whether clinical features affect these indices.

Methods

In this single-centre, retrospective study, we considered children and adolescents with FCD-associated epilepsy who underwent brain magnetic resonance (MRI), including DTI. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity, and radial diffusivity, were calculated in both FCD and CBP. The DTI indices best discriminating between FCD and CBP were subsequently used to assess the link between DTI and selected clinical and lesion-related parameters.

Results

We enrolled 32 patients (20 male; median age at MRI 4 years), including 15 with histologically confirmed FCD. FA values were lower (p = 0.03), whereas MD values were higher in FCD than in CBP (p = 0.04). The difference in FA values between FCD and CBP was more pronounced for a positive vs. negative history of status epilepticus (p = 0.004). Among histologically confirmed cases, the difference in FA values between FCD and CBP was more pronounced for type IIb versus type I FCD (p = 0.03).

Conclusions

FA and MD discriminate between FCD and CBP, while FA differentiates between FCD types. Status epilepticus increases differences in FA, potentially reflecting changes induced in the brain. Our findings support the potential of DTI to serve as a non-invasive biomarker to characterise FCD in the paediatric population.
Undergraduate radiology education in Europe in 2022: a survey from the European Society of Radiology (ESR)
Authors:   European Society of Radiology (ESR), Sendra-Portero Francisco , Souto Miguel , Becker Minerva , Goh Vicky ,   ESR Undergraduate Subcommittee
Published: February 2023

Background

Education in radiology should be an integral aspect of undergraduate medical training given the essential role of imaging in patient management. Since the introduction of the European Society of Radiology undergraduate curriculum a decade ago, radiology education has evolved.

Objectives

This survey aimed to assess the current status of undergraduate radiology education in Europe.

Methods

An electronic survey on undergraduate teaching was distributed by the European Society of Radiology to delegates of the European Society of Radiology education committee and presidents of national radiological societies from April 1 to May 31, 2022. Data from the twenty questions were summarized using descriptive statistics.

Results

There were 72 respondents from 36 countries. Radiology was taught to undergraduates in 95% (68/72), with a national or local curriculum informing radiology education in 93% (67/72). Radiology teaching was delivered by radiologists in 98% (58/59), across all years of medical school but most commonly in the fourth year of medical training (63%, 44/70), through various means including lectures, workshops, radiology department placements, online resources and simulation. Teaching hours were variable, with a minimum of 10 h reported.

Conclusion

This survey’s findings suggest an improvement over the last decade in the engagement of radiologists in the delivery of undergraduate radiology education in European countries affiliated with the European Society of Radiology.
Sex differences in hearing impairment due to diet-induced obesity in CBA/Ca mice
Authors: Kim Soo Jeong , Gajbhiye Akanksha , Lyu Ah-Ra , Kim Tae Hwan , Shin Sun-Ae , Kwon Hyuk Chan , Park Yong-Ho , Park Min Jung
Published: February 2023

Background

Obesity is an independent risk factor for hearing loss. Although attention has focused on major obesity comorbidities such as cardiovascular disease, stroke, and type 2 diabetes, the impact of obesity on sensorineural organs, including the auditory system, is unclear. Using a high-fat diet (HFD)-induced obese mouse model, we investigated the impact of diet-induced obesity on sexual dimorphism in metabolic alterations and hearing sensitivity.

Methods

Male and female CBA/Ca mice were randomly assigned to three diet groups and fed, from weaning (at 28 days) to 14 weeks of age, a sucrose-matched control diet (10 kcal% fat content diet), or one of two HFDs (45 or 60 kcal% fat content diets). Auditory sensitivity was evaluated based on the auditory brainstem response (ABR), distortion product otoacoustic emission (DPOAE), and ABR wave 1 amplitude at 14 weeks of age, followed by biochemical analyses.

Results

We found significant sexual dimorphism in HFD-induced metabolic alterations and obesity-related hearing loss. Male mice exhibited greater weight gain, hyperglycemia, increased ABR thresholds at low frequencies, elevated DPOAE, and lower ABR wave 1 amplitude compared to female mice. The hair cell (HC) ribbon synapse (CtBP2) puncta showed significant sex differences. The serum concentration of adiponectin, an otoprotective adipokine, was significantly higher in female than in male mice; cochlear adiponectin levels were elevated by HFD in female but not male mice. Adiponectin receptor 1 (AdipoR1) was widely expressed in the inner ear, and cochlear AdipoR1 protein levels were increased by HFD, in female but not male mice. Stress granules (G3BP1) were significantly induced by the HFD in both sexes; conversely, inflammatory (IL-1β) responses were observed only in the male liver and cochlea, consistent with phenotype HFD-induced obesity.

Conclusions

Female mice are more resistant to the negative effects of an HFD on body weight, metabolism, and hearing. Females showed increased peripheral and intra-cochlear adiponectin and AdipoR1 levels, and HC ribbon synapses. These changes may mediate resistance to HFD-induced hearing loss seen in female mice.
Predicting RP-LC retention indices of structurally unknown chemicals from mass spectrometry data
Authors: Boelrijk Jim , van Herwerden Denice , Ensing Bernd , Forré Patrick , Samanipour Saer
Published: February 2023

Non-target analysis combined with liquid chromatography high resolution mass spectrometry is considered one of the most comprehensive strategies for the detection and identification of known and unknown chemicals in complex samples. However, many compounds remain unidentified due to data complexity and limited number structures in chemical databases. In this work, we have developed and validated a novel machine learning algorithm to predict the retention index (r$$_i$$

i

) values for structurally (un)known chemicals based on their measured fragmentation pattern. The developed model, for the first time, enabled the predication of r$$_i$$

i

values without the need for the exact structure of the chemicals, with an $$R^2$$

R
2

of 0.91 and 0.77 and root mean squared error (RMSE) of 47 and 67 r$$_i$$

i

units for the NORMAN ($$n=3131$$

n
=
3131

) and amide ($$n=604$$

n
=
604

) test sets, respectively. This fragment based model showed comparable accuracy in r$$_i$$

i

prediction compared to conventional descriptor-based models that rely on known chemical structure, which obtained an $$R^2$$

R
2

of 0.85 with an RMSE of 67.
The Environmental Conditions, Treatments, and Exposures Ontology (ECTO): connecting toxicology and exposure to human health and beyond
Authors: Chan Lauren E. , Thessen Anne E. , Duncan William D. , Matentzoglu Nicolas , Schmitt Charles , Grondin Cynthia J. , Vasilevsky Nicole , McMurry Julie A. , Robinson Peter N. , Mungall Christopher J. , Haendel Melissa A.
Published: February 2023

Background

Evaluating the impact of environmental exposures on organism health is a key goal of modern biomedicine and is critically important in an age of greater pollution and chemicals in our environment. Environmental health utilizes many different research methods and generates a variety of data types. However, to date, no comprehensive database represents the full spectrum of environmental health data. Due to a lack of interoperability between databases, tools for integrating these resources are needed. In this manuscript we present the Environmental Conditions, Treatments, and Exposures Ontology (ECTO), a species-agnostic ontology focused on exposure events that occur as a result of natural and experimental processes, such as diet, work, or research activities. ECTO is intended for use in harmonizing environmental health data resources to support cross-study integration and inference for mechanism discovery.

Methods and findings

ECTO is an ontology designed for describing organismal exposures such as toxicological research, environmental variables, dietary features, and patient-reported data from surveys. ECTO utilizes the base model established within the Exposure Ontology (ExO). ECTO is developed using a combination of manual curation and Dead Simple OWL Design Patterns (DOSDP), and contains over 2700 environmental exposure terms, and incorporates chemical and environmental ontologies. ECTO is an Open Biological and Biomedical Ontology (OBO) Foundry ontology that is designed for interoperability, reuse, and axiomatization with other ontologies. ECTO terms have been utilized in axioms within the Mondo Disease Ontology to represent diseases caused or influenced by environmental factors, as well as for survey encoding for the Personalized Environment and Genes Study (PEGS).

Conclusions

We constructed ECTO to meet Open Biological and Biomedical Ontology (OBO) Foundry principles to increase translation opportunities between environmental health and other areas of biology. ECTO has a growing community of contributors consisting of toxicologists, public health epidemiologists, and health care providers to provide the necessary expertise for areas that have been identified previously as gaps.
Statistical actuarial estimation of the Capitation Payment Unit from copula functions and deep learning: historical comparability analysis for the Colombian health system, 2015–2021
Authors: Espinosa Oscar , Bejarano Valeria , Ramos Jeferson , Martínez Boris
Published: February 2023

The Capitation Payment Unit (CPU) financing mechanism constitutes more than 70% of health spending in Colombia, with a budget allocation of close to 60 trillion Colombian pesos for the year 2022 (approximately 15.7 billion US dollars). This article estimates actuarially, using modern techniques, the CPU for the contributory regime of the General System of Social Security in Health in Colombia, and compares it with what is estimated by the Ministry of Health and Social Protection. Using freely available information systems, by means of statistical copulas functions and artificial neural networks, pure risk premiums are calculated between 2015 and 2021. The study concludes that the weights by risk category are systematically different, showing historical pure premiums surpluses in the group of 0–1 years and deficits (for the regions normal and cities) in the groups over 54 years of age.
Biochemical characterization of extremozyme L-asparaginase from Pseudomonas sp. PCH199 for therapeutics
Authors: Darnal Sanyukta , Patial Vijeta , Kumar Virender , Kumar Subhash , Kumar Vijay , Padwad Yogendra S. , Singh Dharam
Published: February 2023

L-asparaginase (L-ASNase) from microbial sources is a commercially vital enzyme to treat acute lymphoblastic leukemia. However, the side effects associated with the commercial formulations of L-ASNases intrigued to explore for efficient and desired pharmacological enzymatic features. Here, we report the biochemical and cytotoxic evaluation of periplasmic L-ASNase of Pseudomonas sp. PCH199 isolated from the soil of Betula utilis, the Himalayan birch. L-ASNase production from wild-type PCH199 was enhanced by 2.2-fold using the Response Surface Methodology (RSM). Increased production of periplasmic L-ASNase was obtained using an optimized osmotic shock method followed by its purification. The purified L-ASNase was a monomer of 37.0 kDa with optimum activity at pH 8.5 and 60 ℃. It also showed thermostability retaining 100.0% (200 min) and 90.0% (70 min) of the activity at 37 and 50 ℃, respectively. The Km and Vmax values of the purified enzyme were 0.164 ± 0.009 mM and 54.78 ± 0.4 U/mg, respectively. L-ASNase was cytotoxic to the K562 blood cancer cell line (IC50 value 0.309 U/mL) within 24 h resulting in apoptotic nuclear morphological changes as examined by DAPI staining. Therefore, the dynamic functionality in a wide range of pH and temperature and stability of PCH199 L-ASNase at 37 ℃ with cytotoxic potential proves to be pharmaceutically important for therapeutic application.
Enhanced liquidity of p62 droplets mediated by Smurf1 links Nrf2 activation and autophagy
Authors: Xia Qin , Li Yang , Xu Wanting , Wu Chengwei , Zheng Hanfei , Liu Liqun , Dong Lei
Published: February 2023

Background

Macro-autophagy/Autophagy is an evolutionarily well-conserved recycling process to maintain the balance through precise spatiotemporal regulation. However, the regulatory mechanisms of biomolecular condensates by the key adaptor protein p62 via liquid-liquid phase separation (LLPS) remain obscure.

Results

In this study, we showed that E3 ligase Smurf1 enhanced Nrf2 activation and promoted autophagy by increasing p62 phase separation capability. Specifically, the Smurf1/p62 interaction improved the formation and material exchange of liquid droplets compared with p62 single puncta. Additionally, Smurf1 promoted the competitive binding of p62 with Keap1 to increase Nrf2 nuclear translocation in p62 Ser349 phosphorylation-dependent manner. Mechanistically, overexpressed Smurf1 increased the activation of mTORC1 (mechanistic target of rapamycin complex 1), in turn leading to p62 Ser349 phosphorylation. Nrf2 activation increased the mRNA levels of Smurf1, p62, and NBR1, further promoting the droplet liquidity to enhance oxidative stress response. Importantly, we showed that Smurf1 maintained cellular homeostasis by promoting cargo degradation through the p62/LC3 autophagic pathway.

Conclusions

These findings revealed the complex interconnected role among Smurf1, p62/Nrf2/NBR1, and p62/LC3 axis in determining Nrf2 activation and subsequent clearance of condensates through LLPS mechanism.
On the distribution-tail behaviour of the product of normal random variables
Authors: Leipus Remigijus , Šiaulys Jonas , Dirma Mantas , Zovė Romualdas
Published: February 2023

In this paper we consider the product$\Pi _{n}=\prod_{k=1}^{n}\xi _{k}$Πn=∏k=1nξkofnindependent normally distributed zero mean random variables$\xi _{1},\dots ,\xi _{n}$ξ1,…,ξn. We derive an asymptotic formula for the survival probability${\mathbb{P}}(\Pi _{n}>x)$P(Πn>x), as$x\to \infty $x→∞, with the first remaining term.
Safety and preliminary outcomes of short-acting opioid agonist treatment (sOAT) for hospitalized patients with opioid use disorder
Authors: Thakrar Ashish P. , Uritsky Tanya J. , Christopher Cara , Winston Anna , Ronning Kaitlin , Sigueza Anna Lee , Caputo Anne , McFadden Rachel , Olenik Jennifer M. , Perrone Jeanmarie , Delgado M. Kit , Lowenstein Margaret , Compton Peggy
Published: February 2023

Background

Patients with opioid use disorder (OUD) frequently leave the hospital as patient directed discharges (PDDs) because of untreated withdrawal and pain. Short-acting opioids can complement methadone, buprenorphine, and non-opioid adjuvants for withdrawal and pain, however little evidence exists for this approach. We described the safety and preliminary outcomes of short-acting opioid agonist treatment (sOAT) for hospitalized patients with OUD at an academic hospital in Philadelphia, PA.

Methods

From August 2021 to March 2022, a pharmacist guided implementation of a pilot sOAT protocol consisting of escalating doses of oxycodone or oral hydromorphone scheduled every four hours, intravenous hydromorphone as needed, and non-opioid adjuvants for withdrawal and pain. All patients were encouraged to start methadone or buprenorphine treatment for OUD. We abstracted data from the electronic health record into a secure platform. The primary outcome was safety: administration of naloxone, over-sedation, or a fall. Secondary outcomes were PDDs and respective length of stay (LOS), discharges on methadone or buprenorphine, and discharges with naloxone. We compared secondary outcomes to hospitalizations in the 12 months prior to the index hospitalization among the same cohort.

Results

Of the 23 cases, 13 (56.5%) were female, 19 (82.6%) were 40 years or younger, and 22 (95.7%) identified as White. Twenty-one (91.3%) regularly injected opioids and four (17.3%) were enrolled in methadone or buprenorphine prior to hospitalization. sOAT was administered at median doses of 200–320 morphine milligram equivalents per 24-h period. Naloxone administration was documented once in the operating room, over-sedation was documented once after unsanctioned opioid use, and there were no falls. The PDD rate was 44% with median LOS 5 days (compared to PDD rate 69% with median LOS 3 days for prior admissions), 65% of sOAT cases were discharged on buprenorphine or methadone (compared to 33% for prior admissions), and 65% of sOAT cases were discharged with naloxone (compared to 19% for prior admissions).

Conclusions

Pilot implementation of sOAT was safe. Compared to prior admissions in the same cohort, the PDD rate was lower, LOS for PDDs was longer, and more patients were discharged on buprenorphine or methadone and with naloxone, however efficacy for these secondary outcomes remains to be established.
Do geography and institutions affect entrepreneurs’ future business plans? Insights from Greece
Authors: Rasvanis Evangelos , Tselios Vassilis
Published: February 2023

It is widely known that both geography and institutions determine the location of an investment. However, little is known about the impact of these factors on entrepreneurs’ future business plans. Using a questionnaire survey, this paper examines whether the 'first-' and 'second-nature' geography and institutions affect the plans of entrepreneurs to expand or sell their businesses in Greece. The analysis shows that entrepreneurs intend to expand their businesses when the importance of the country's relative geographical location to the international market increases, but that of localisation economies decreases. There is also evidence that entrepreneurs aim to sell their businesses to domestic investors when sea access, the natural environment, the agglomeration economies, the location of Greece and the local governance are ideal for the business performance in the country.
miR-6076 rs1463411 polymorphisms are associated with bleeding during clopidogrel treatment in patients with acute coronary syndrome
Authors: Mo Zhen-Zhen , Yuan Zhen , Peng Yuan-Yuan , Zhou Wan-Lu , Dai Wei , Wang Guo , Tang Jie , Zhang Wei , Chen Bi-Lian
Published: February 2023

Bleeding is a major adverse event during clopidogrel treatment in patients with acute coronary syndrome (ACS). However, the potential mechanism affecting bleeding among individuals is unclear. Herein, we investigated the involvement of CYP2C19*2 and CYP2C19*3, as well as 10 miRNA polymorphisms, in bleeding in Chinese patients with ACS during the first year of clopidogrel treatment. The miR-6076 rs1463411 G polymorphism was significantly associated with the risk of bleeding (P < 0.001), and the rs1463411 GT + GG genotype significantly increased the risk of bleeding (adjusted odds ratio, 6.09; 95% confidence interval, 1.09–34.0; P < 0.001). Dual luciferase assay showed that miR-6076 significantly decreased the mRNA expression of P2RY12 (P < 0.05). P2RY12 mRNA and protein levels were significantly lower in cells transfected with miR-6076-G than in cells transfected with miR-6076-T (P < 0.05). The findings indicate that miR-6076 targets P2RY12 mRNA and that miR-6076 rs1463411 T/G polymorphisms differentially regulate P2RY12 mRNA and protein levels in cells. rs1463411 G polymorphism may increase the risk of bleeding during clopidogrel treatment in patients with ACS.
Experimental Evaluation of Shape Memory Alloy Retrofitting Effect for Circular Concrete Column Using Ultrasonic Pulse Velocity
Authors: Lee Taemin , Jeong Saebyeok , Woo Ukyong , Choi Hajin , Jung Donghyuk
Published: February 2023

The seismic performance of a concrete column retrofitted with an iron-based shape memory alloy (Fe-SMA) was evaluated under cyclic loading. In addition to structural behavior, internal damage was monitored using an ultrasonic pulse velocity test. The round shapes of three reinforced concrete (RC) columns were tested: a non-retrofitted RC column as a control, a carbon fiber-reinforced polymer (CFRP) column, and an Fe-SMA retrofitted column. During the cyclic loading test, the degradation of the column was defined based on the decrease in compressional wave velocities. The experimental results demonstrated a maximum improvement of 175% in seismic performance of the Fe-SMA retrofitted RC column compared with the controlled column. This is primarily owing to the active constraints of the SMA, which were quantified based on ultrasonic velocities. Furthermore, the surface degradation process was identified using external cracks, which were not visible in the CFRP retrofitted RC column.
Selective footprints and genes relevant to cold adaptation and other phenotypic traits are unscrambled in the genomes of divergently selected chicken breeds
Authors: Romanov Michael N. , Abdelmanova Alexandra S. , Fisinin Vladimir I. , Gladyr Elena A. , Volkova Natalia A. , Koshkina Olga A. , Rodionov Andrey N. , Vetokh Anastasia N. , Gusev Igor V. , Anshakov Dmitry V. , Stanishevskaya Olga I. , Dotsev Arsen V. , Griffin Darren K. , Zinovieva Natalia A.
Published: February 2023

Background

The genomes of worldwide poultry breeds divergently selected for performance and other phenotypic traits may also be affected by, and formed due to, past and current admixture events. Adaptation to diverse environments, including acclimation to harsh climatic conditions, has also left selection footprints in breed genomes.

Results

Using the Chicken 50K_CobbCons SNP chip, we genotyped four divergently selected breeds: two aboriginal, cold tolerant Ushanka and Orloff Mille Fleur, one egg-type Russian White subjected to artificial selection for cold tolerance, and one meat-type White Cornish. Signals of selective sweeps were determined in the studied breeds using three methods: (1) assessment of runs of homozygosity islands, (2) FST based population differential analysis, and (3) haplotype differentiation analysis. Genomic regions of true selection signatures were identified by two or more methods or in two or more breeds. In these regions, we detected 540 prioritized candidate genes supplemented them with those that occurred in one breed using one statistic and were suggested in other studies. Amongst them, SOX5, ME3, ZNF536, WWP1, RIPK2, OSGIN2, DECR1, TPO, PPARGC1A, BDNF, MSTN, and beta-keratin genes can be especially mentioned as candidates for cold adaptation. Epigenetic factors may be involved in regulating some of these important genes (e.g., TPO and BDNF).

Conclusion

Based on a genome-wide scan, our findings can help dissect the genetic architecture underlying various phenotypic traits in chicken breeds. These include genes representing the sine qua non for adaptation to harsh environments. Cold tolerance in acclimated chicken breeds may be developed following one of few specific gene expression mechanisms or more than one overlapping response known in cold-exposed individuals, and this warrants further investigation.
Functions and mechanisms of lncRNA MALAT1 in cancer chemotherapy resistance
Authors: Hou Junhui , Zhang Gong , Wang Xia , Wang Yuan , Wang Kefeng
Published: February 2023

Chemotherapy is one of the most important treatments for cancer therapy. However, chemotherapy resistance is a big challenge in cancer treatment. Due to chemotherapy resistance, drugs become less effective or no longer effective at all. In recent years, long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been found to be associated with the development of chemotherapy resistance, suggesting that MALAT1 may be an important target to overcome chemotherapy resistance. In this review, we introduced the main mechanisms of chemotherapy resistance associated with MALAT1, which may provide new approaches for cancer treatment.
Cannabis use amongst tinnitus patients: Consumption patterns and attitudes
Authors: Mavedatnia Dorsa , Levin Marc , Lee Jong Wook , Hamour Amr F. , Dizon Kaye , Le Trung
Published: February 2023

Background

Tinnitus has a significant impact on quality of life and causes considerable psychological distress. Cannabis is known to modulate neuron hyperexcitability, provide protection against auditory damage, and has been used for treatment for many diseases which have physiological similarities with tinnitus. The objective of this study was to survey patients presenting with tinnitus regarding their perspectives and usage patterns of cannabis.

Methods

Patients with a primary presenting complaint of tinnitus in a tertiary neuro-otology clinic completed a 18-item questionnaire assessing perception, attitudes, and cannabis usage patterns.

Results

Forty five patients completed the survey (mean age: 54.5 years, 31 females and 14 males). Overall, 96% of patients reported that they would consider cannabis as treatment for their tinnitus. Patients considered cannabis use for auditory symptoms (91%), and symptoms related to their tinnitus, such as emotional complaints (60%), sleep disturbances (64%), and functional disturbances (56%). 36% of patients had previously used cannabis and 22% of patients reported cannabis use at the time of the study. 80% of patients that were actively using cannabis reported that it helped with tinnitus-related symptoms, such as dizziness, anxiety, bodily pain, and sleep disturbances. Most patients would prefer to use edibles (62%), tablet (58%) and cream (47%) formulations of cannabis. Patients were concerned about the cost (29%), potential physical health implications (53%) and psychosocial side effects (60%) of cannabis. Over half of patients learned about cannabis from a friend or family member and only 22% of patients learned about cannabis from a physician or nurse.

Conclusion

Cannabis use is common amongst patients with tinnitus and current users of cannabis reported that it helped with their symptoms. Most patients would consider its use as a potential treatment to alleviate their tinnitus-related symptoms and are interested in learning more regarding its use. By understanding how cannabis is perceived by tinnitus patients, healthcare providers can provide appropriate patient education.

Graphical Abstract
UHPLC‐Q‐TOF‐MS/MS‐guided dereplication to study chemical constituents of Hedera nepalensis leaves in northern Vietnam
Authors: Ngoc Pham Hong , An Tran Chieu , Hiep Nguyen Tuan , Nhu Tran Phan Huynh , Hung Le Ngoc , Trung Nguyen Quang , Minh Bui Quang , Van Trung Phung
Published: February 2023

Hedera nepalensis is commonly used as a traditional medicine for the treatment of several diseases. In this research, the efficient characterization of chemical constituents, especially triterpenoid saponins, contained in H. nepalensis extract was established by applying ultra‐high‐performance liquid chromatography‐quadrupole time‐of‐flight tandem mass spectrometry method (UHPLC‐Q‐TOF‐MS/MS). As a result, a total of 45 compounds including 21 triterpene saponins were tentatively elucidated based on MS and MS/MS data, in which eight structures have been reported for the first time. This study provided an efficient analysis strategy to rapidly determine the chemical constituents and laid a foundation for future study of H. nepalensis planted in Northern Vietnam and other Hedera species.
In silico toxicity assessment and trace level quantification of two genotoxic impurities in silodosin using capillary gas chromatography
Authors: Panchakarla Ravi Kiran , Ravi Punna Rao , Buddha Manidhar Syam Kumar , Mullangi Sumanth , Kondapalli Venkata Gowri Chandra Sekhar
Published: February 2023

A capillary gas chromatographic method using flame ionization detection was developed and validated for the trace quantification of 2-bromoethanol (2-BE) and 2-bromoethylmethanesulfonate (2-BEM) in silodosin, used in the treatment of benign prostatic hyperplasia. Chromatographic separation was performed in spilt mode using nitrogen as carrier gas on a column containing crosslinked polyethylene glycol (30 m × 0.32 mm, 0.25 µm) stationary phase modified with nitroterephthalic acid. A simple matrix precipitation strategy was implemented to eliminate the sample overload and the matrix interference problems. The developed method was linear and accurate in the concentration range of 24–3000 ppm for 2-BE and 24–300 ppm for 2-BEM with r2 ˃ 0.999 and percent recoveries greater than 90% for both the analytes. The developed method was precise for both the analytes with RSD(%) of not more than 4.5%. In silico genotoxicity and carcinogenicity potential of 2-BEM were assessed using ICH M7 principles. The developed method can be applied in the quality control laboratories of pharmaceutical industries for trace level quantification of 2-BE and 2-BEM in silodosin.
Testing determinations of Thellier paleointensities on 1962 and 1983 lava flows and scoriae in Miyakejima, Japan
Authors: Fukuma Koji
Published: February 2023

Using a fully automated magnetometer, test measurements of paleointensity by the Thellier method were performed on basaltic lava sections, including upper and lower clinkers through the lava interior, and scoriae that erupted from Miyakejima Volcano in 1962 and 1983. Curie temperatures showed a bimodal distribution with titanium-rich and -poor titanomagnetites, and in many cases two phases coexisted in a single sample. Thermomagnetic analyses on all samples prior to the Thellier measurements helped set appropriate temperature steps during Thellier measurements for individual samples. The Thellier results were selected using a combination of TTA and curvature criteria to detect thermal alteration and multidomain effects. Two-thirds of the clinker and scoria samples passed the criteria, which is 4.3 times higher compared to the lava interior. Paleointensities at all six sites are not largely different from the expected geomagnetic field intensities, and the averaged paleointensities for the 1962 and 1983 lavas/scoriae are within 5% of the expected intensities. Pass and fail samples have distinctly different hysteresis properties with a threshold ratio of saturation remanence to saturation magnetization ($$M_{\rm r}/M_{\rm s}$$

M
r

/

M
s

) at 0.22. To obtain reliable Thellier paleointensities on volcanic rocks, rapidly cooled clinkers and scoriae are to be collected, screened for the hysteresis properties, and then heated according to the temperature steps assigned to each sample.

Graphical abstract
Historical regional climate changes in Japan in winter as assessed by a 5-km regional climate model with a land surface process
Authors: Kawase Hiroaki , Fukui Shin , Nosaka Masaya , Watanabe Shun-ichi I. , Otomo Keishi , Murata Akihiko , Murazaki Kazuyo , Nakaegawa Tosiyuki
Published: February 2023

We investigate historical regional climate changes in Japan from 1959 to 2020, analyzing a high-resolution dynamical downscaling forced by the Japanese 55-year Reanalysis (JRA-55). One-year continuous simulations are conducted by the non-hydrostatic regional climate model with a land surface model that includes the snow accumulation process, which enables us to evaluate the seasonal variation of snow cover in all of Japan. Our simulation reproduces interannual variations of the annual mean surface air temperature and annual total precipitation, and it shows rapid warming since around 1980. The annual maximum snow depth and annual maximum daily snowfall show significant decreasing trends at lower elevations on the Japan Sea sides of eastern and western Japan. Areas at higher elevations in eastern Japan show no trend in the maximum snow depth and a significant increasing trend in the maximum daily snowfall. In northern Japan, altitudinal dependencies in snow depth and snowfall changes are smaller on the Japan Sea side than on the Pacific Ocean side: the Japan Sea side shows insignificant changes in snow depth at all elevations, while the Pacific Ocean side shows decreasing and significant increasing trends at lower and higher elevations, respectively. The total number of snow-covered days is decreasing at most elevations in all regions, while the rate of decrease is smaller at higher elevations and latitudes. Composite analyses of annual maximum daily snowfall events at one prefectural city facing the Japan Sea in central Japan indicate that heavy daily snowfall occurs when the Japan Polar air mass Convergence Zone appears over the Japan Sea and the snowfall amounts show increasing and decreasing trends over the mountainous and coastal areas, respectively, due to historical warming and moistening. Our results are basically consistent with previous studies that have focused on future changes in snow depth and snowfall.
A SafeML extension for a unified risk assessment to diverse service robots
Authors: Miyoshi Takao , Nakabo Yoshihiro , Fukui Hidetoshi , Yashiro Makoto , Miyazawa Iko , Sakamoto Takeshi , Ando Noriaki , Kuga Toru , Kitamura Atsushi , Ohara Kenichi , Kimura Tetsuya
Published: February 2023

Risk assessment is one of the important processes in the social implementation of robots. In risk assessment and safety design of systems with various stakeholders, modeling and visualization of related elements are important not only for designers but also for users. We examined the use of SafeML in the process and proposed its extension for the purpose for missing elements.
Epidemiology, biology, pathogenesis, clinical manifestations, and diagnosis of dengue virus infection, and its trend in Ethiopia: a comprehensive literature review
Authors: Zerfu Biruk , Kassa Tesfu , Legesse Mengistu
Published: February 2023

Dengue fever is a dengue virus infection, emerging rapidly and posing public health threat worldwide, primarily in tropical and subtropical countries. Nearly half of the world's population is now at risk of contracting the dengue virus, including new countries with no previous history-like Ethiopia. However, little is known about the epidemiology and impact of the disease in different countries. This is especially true in countries, where cases have recently begun to be reported. This review aims to summarize epidemiology, biology, pathogenesis, clinical manifestations, and diagnosis of dengue virus infection and its trend in Ethiopia. It may help countries, where dengue fever is not yet on the public health list-like Ethiopia to alert healthcare workers to consider the disease for diagnosis and treatment. The review retrieved and incorporated 139 published and organizational reports showing approximately 390 million new infections. About 100 million of these infections develop the clinical features of dengue, and thousands of people die annually from severe dengue fever in 129 countries. It is caused by being bitten by a dengue virus-infected female mosquito, primarilyAedes aegyptiand, lesser,Ae. albopictus. Dengue virus is a member of theFlavivirusgenus of theFlaviviridaefamily and has four independent but antigen-related single-stranded positive-sense RNA virus serotypes. The infection is usually asymptomatic but causes illnesses ranging from mild febrile illness to fatal dengue hemorrhagic fever or shock syndrome. Diagnosis can be by detecting the virus genome using nucleic acids amplification tests or testing NS1 antigen and/or anti-dengue antibodies from serum, plasma, circulating blood cells, or other tissues. Dengue cases and outbreaks have increased in recent decades, with a significant public health impact. Ethiopia has had nearly annual outbreaks since 2013, devastating an already fragmented health system and economy. Standardization of medication, population-level screening for early diagnosis and prompt treatment, and minimization of mosquito bites reduce overall infection and mortality rates.
Clinical application of headache impact test (HIT)-6 and epworth sleepiness scale (ESS) for sleep apnea headache
Authors: Tabata Hiromitsu , Kinoshita Masako , Taniguchi Mitsutaka , Ooi Motoharu
Published: February 2023

Background

Sleep apnea headache is a major symptom accompanying obstructive sleep apnea (OSA), but relatively little evidence has been reported on the magnitude of its negative effects on patients or the evaluation of therapeutic effects. We quantitatively assessed sleep apnea headache using the Epworth sleepiness scale (ESS) and headache impact test (HIT)-6.

Methods

The first part of this study enrolled 86 patients (72 male; mean [± standard deviation] age 53.2 ± 13.8 years) who had been diagnosed with OSA by polysomnography in our sleep center and investigated the prevalence and characteristics of sleep apnea headache. The second part enrolled 21 patients (12 male; mean age, 47.5 ± 13.0 years) diagnosed with sleep apnea headache by polysomnography and/or peripheral arterial tonometry and evaluated the effects of OSA therapy on headache. Medical records including ESS, HIT-6, and polysomnographic data were retrospectively analyzed.

Results

The prevalence of sleep apnea headache among OSA patients was 22.1%, and was higher in female (50.0%) than in male (16.7%). The proportion of N3 and HIT-6 score showed a significant negative correlation (Pearson’s R = -0.51, p < 0.05). In female, median apnea–hypopnea index (AHI) was significantly lower in patients with headache (26.1 /h [interquartile range 21.4–29.6 /h]) than in patients without (54.2 /h [41.3–73.9 /h], p < 0.05, Wilcoxon rank-sum test). HIT-6 and ESS scores improved from 56.4 ± 9.7 to 45.9 ± 8.4 and from 9.0 ± 4.4 to 5.3 ± 4.2 in patients with oral appliance (OA), and from 54.3 ± 10.7 to 44.6 ± 6.1 and from 10.0 ± 4.0 to 4.9 ± 2.9 with continuous positive airway pressure (CPAP). In patients with good CPAP adherence, these scores improved from 58.1 ± 10.8 to 44.0 ± 6.0 and from 9.6 ± 3.8 to 3.6 ± 1.7.

Conclusion

Among patients with OSA, prevalence of sleep apnea headache was higher in female than in male. In female, headache was associated with relatively mild OSA. OA showed substantial effects on headache in mild to moderate OSA patients. CPAP adherence was important for improving the headache. HIT-6 score appears useful for the diagnosis and management of sleep apnea headache.
Assessment of genotoxic effects of wastewater of Kitchener pool, Nile Delta Region, North Egypt, using Allium test
Authors: El-Kholy Aziza S. , Haroun Soliman A. , Labeeb May
Published: February 2023

Background

In the present study, Allium test bioassay was utilized to evaluate the effects of mixed wastewater of agricultural and sewage effluents at Kitchener pool, Gharbia governate, Middle Delta region, North Egypt. Germination indices, mitotic index and aberrations, α, β-esterase isozymes and inter-simple sequence repeat (ISSR) fingerprinting were tested by different concentrations of the wastewater (tap water as control, 25%, 50% and 100% wastewater).

Results

Water analysis recorded high levels of electrical conductivity, cations and anions compared to control, but were in the permitted limits according to FAO (Food and Agricultural Organization) except Mg2+ and K1+ were above the limits. P, N and heavy metals as Pb, Mn and Ni were also higher than the control. Germination indices showed reduction for all parameters studied (root and shoot lengths, root and shoot fresh and dry weights, and tolerance index). Mitotic index decreased, and the percentage of mitotic aberrations increased as the concentration of treatments increased and the time prolonged. Different types of aberrations were recorded in all treatments and its percentage is time and dose independent. Goat cells are the most common type recorded after different times in all treatments. The expression of α, β-esterase enzymes showed variation in different treatments compared to control and ISSR profiles showed considerable polymorphism. Concentration of 25% mixed water induced different profiles for expression of both α- and β-esterase from other treatments, and the cluster analysis based on polymorphism in ISSR fingerprinting revealed the distinction of plants treated with this concentration and the control plants from those treated with high concentrations.

Conclusion

It was suggested that concentration of 25% mixed water may be suitable for growth and act as fertilizer. Mixed water from this pool may be genotoxic for Allium cepa plants at early growth if it is used for irrigation in its present form and usage of this wastewater for agricultural purposes may be harmful and must be partially treated and biologically tested before use.
Estrogen Receptor Status by Immunohistochemistry Is Superior to the Ligand-Binding Assay for Predicting Response to Adjuvant Endocrine Therapy in Breast Cancer
Authors: Harvey Jennet M. , Clark Gary M. , Osborne C. Kent , Allred D. Craig
Published: February 2023

PURPOSE

Immunohistochemistry (IHC) is a newer technique for assessing the estrogen receptor (ER) status of breast cancers, with the potential to overcome many of the shortcomings associated with the traditional ligand-binding assay (LBA). The purpose of this study was to evaluate the ability of ER status determination by IHC, compared with LBA, to predict clinical outcome—especially response to adjuvant endocrine therapy—in a large number of patients with long-term clinical follow-up.

PATIENTS AND METHODS

ER status was evaluated in 1,982 primary breast cancers by IHC on formalin-fixed paraffin-embedded tissue sections, using antibody 6F11 and standard methodology. Slides were scored on a scale representing the estimated proportion and intensity of positive-staining tumor cells (range, 0 to 8). Results were compared with ER values obtained by the LBA in the same tumors and to clinical outcome.

RESULTS

An IHC score of greater than 2 (corresponding to as few as 1% to 10% weakly positive cells) was used to define ER positivity on the basis of a univariate cut-point analysis of all possible scores and disease-free survival (DFS) in patients receiving any adjuvant endocrine therapy. Using this definition, 71% of all tumors were determined to be ER-positive by IHC, and the level of agreement with the LBA was 86%. In multivariate analyses of patients receiving adjuvant endocrine therapy alone, ER status determined by IHC was better than that determined by the LBA at predicting improved DFS (hazard ratios/ P = 0.474/.0008 and 0.707/.3214, respectively) and equivalent at predicting overall survival (0.379/.0001 and 0.381/.0003, respectively).

CONCLUSION

IHC is superior to the LBA for assessing ER status in primary breast cancer because it is easier, safer, and less expensive, and has an equivalent or better ability to predict response to adjuvant endocrine therapy.
Berberine Ameliorates Obesity by Inducing GDF15 Secretion by Brown Adipocytes
Authors: Li Chang , Leng Qingyang , Li Lihua , Hu Fan , Xu Yuejie , Gong Sa , Yang Ying , Zhang Hongli , Li Xiaohua
Published: February 2023

Berberine (BBR), which is a compound derived from the Chinese medicinal plant Coptis chinensis, promotes weight loss, but the molecular mechanisms are not well understood. Here, we show that BBR increases the serum level of growth differentiation factor 15 (GDF15), which is a stress response cytokine that can reduce food intake and lower body weight in diet-induced obese (DIO) mice. The body weight and food intake of DIO mice were decreased after BBR treatment, and the weight change was negatively correlated with the serum GDF15 level. Further studies show that BBR induced GDF15 mRNA expression and secretion in the brown adipose tissue (BAT) of DIO mice and primary mouse brown adipocytes. In addition, we found that BBR upregulates GDF15 mRNA expression and secretion by activating the integrated stress response (ISR) in primary mouse brown adipocytes. Overall, our findings show that BBR lowers body weight by inducing GDF15 secretion via the activation of the ISR in BAT.
Bartter Syndrome Type 1 Due to Novel SLC12A1 Mutations Associated With Pseudohypoparathyroidism Type II
Authors: Kiuchi Zentaro , Nozu Kandai , Yan Kunimasa , Jüppner Harald
Published: February 2023

Bartter syndrome type 1 is caused by mutations in the solute carrier family 12 member 1 (SLC12A1), encoding the sodium-potassium-chloride cotransporter-2 (NKCC2). In addition to causing renal salt-losing tubulopathy, SLC12A1 mutations are known to cause nephrocalcinosis due to hypercalciuria, as well as failure to thrive associated with abnormal calcium and phosphorus homeostasis. We report a now 7-year-old Japanese girl with polyuria, hyponatremia, hypokalemia, and metabolic alkalosis, in whom compound heterozygous novel SLC12A1 mutations were identified. Elevated parathyroid hormone (PTH) levels were consistently noted after the age of 1 year in conjunction with gradually declining serum calcium and increasing serum phosphorus levels. To confirm suspected PTH-resistance, Ellsworth Howard tests were performed at the ages of 6 years 8 months and 6 years 10 months in the absence or presence of ibuprofen, respectively. Urinary adenosine 3′,5′-cyclic monophosphate excretion increased on both occasions in response to PTH(1-34) infusion suggesting pseudohypoparathyroidism type II. However, only during treatment with ibuprofen did PTH induce an almost normal phosphaturic response. The nonsteroidal anti-inflammatory drugs thus enhanced growth velocity, alleviated hypercalciuria, and increased PTH-stimulated urinary phosphorus excretion without significantly affecting renal function.