bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical outcomes of new multifocal intraocular lenses with hydroxyethyl methacrylate and comparative results of contrast sensitivity, objective scatter, and subjective photic phenomena
Authors: Lee Yong Woo , Choi Chul Young , Moon Kun , Jeong Yong Jin , An Sang Il , Lee Je Myung , Lee Jong Ho , Seong Min Cheol
Published: September 2022

Background

We investigate the performance of new hydrophobic diffractive multifocal intraocular lenses (IOL) with hydroxyethyl methacrylate (HEMA) and compare their optical quality, contrast sensitivity, and subjective photic phenomena.

Methods

Medical records of patients who underwent routine simple cataract surgery and insertion of an existing multifocal IOL (TFNT, TF group) or a new multifocal IOL (CNWT, CN group) were retrospectively reviewed. Clinical data was collected 2 months postoperatively and included optical quality analysis system (OQAS) indices, contrast sensitivity, and subjective degrees of photic phenomena.

Results

One hundred thirty-five eyes of 135 patients were included (CN group, 71; TF group, 64). There was no significant difference between the two groups in the visual acuity and defocus curve. The indices of OQAS did not show a significant difference between groups. Contrast sensitivity was significantly better in the CN group at all degrees, including the area under the log contrast sensitivity function (p = 0.01). The subjective photic phenomena survey showed better results for the CN group, with the proportion of patients reporting no photic phenomena as 9.9% and 3.1% in the CN and TF groups, respectively. The proportion of patients who reported severe photic phenomena was 11.3% in the CN group and 25.0% in the TF group. Although the follow-up period was only 2 months, glistening, surface scattering, and posterior capsule opacity were not observed in any patient.

Conclusions

The new multifocal IOL with HEMA is safe, and provides stable visual acuity as well as superior contrast sensitivity and lower subjective photic phenomena, over the prior IOL.
Correlating drug prescriptions with prognosis in severe COVID-19: first step towards resource management
Authors: Levin Anna S. , Freire Maristela P. , Oliveira Maura Salaroli de , Nastri Ana Catharina S. , Harima Leila S. , Perdigão-Neto Lauro Vieira , Magri Marcello M. , Fialkovitz Gabriel , Figueiredo Pedro H. M. F. , Siciliano Rinaldo Focaccia , Sabino Ester C. , Carlotti Danilo P. N. , Rodrigues Davi Silva , Nunes Fátima L. S. , Ferreira João Eduardo ,   HCFMUSP COVID-19 Study Group, Filho Geraldo Busatto , Bonfá Eloisa , Utiyama Edivaldo , Segurado Aluisio , Perondi Beatriz , Morais Anna M. , Montal Amanda , Fusco Solange , Fregonesi Marjorie , Rocha Marcelo , Marcilio Izabel , Rios Izabel C. , Fabiane  , Kawano Y. O. , de Jesus M. Amelia , Kallas Esper G. , Marmo Carolina , Tanaka Clarice , de Souza Heraldo P. , Marchini Julio F. M. , Carvalho Carlos , Ferreira Juliana C. , Guimaraes Thais , Lazari Carolina S. , Duarte Alberto J. S. , Braido M. Cristina , Francisco P. B. , Costa Silvia F.
Published: September 2022

Background

Optimal COVID-19 management is still undefined. In this complicated scenario, the construction of a computational model capable of extracting information from electronic medical records, correlating signs, symptoms and medical prescriptions, could improve patient management/prognosis.

Methods

The aim of this study is to investigate the correlation between drug prescriptions and outcome in patients with COVID-19. We extracted data from 3674 medical records of hospitalized patients: drug prescriptions, outcome, and demographics. The outcome evaluated was hospital outcome. We applied correlation analysis using a Logistic Regression algorithm for machine learning with Lasso and Matthews correlation coefficient.

Results

We found correlations between drugs and patient outcomes (death/discharged alive). Anticoagulants, used very frequently during all phases of the disease, were associated with good prognosis only after the first week of symptoms. Antibiotics very frequently prescribed, especially early, were not correlated with outcome, suggesting that bacterial infections may not be important in determining prognosis. There were no differences between age groups.

Conclusions

In conclusion, we achieved an important result in the area of Artificial Intelligence, as we were able to establish a correlation between concrete variables in a real and extremely complex environment of clinical data from COVID-19. Our results are an initial and promising contribution in decision-making and real-time environments to support resource management and forecasting prognosis of patients with COVID-19.
Pathophysiology of reversible cerebral vasoconstriction syndrome
Authors: Chen Shih-Pin , Wang Shuu-Jiun
Published: September 2022

Reversible cerebral vasoconstriction syndrome (RCVS) is a complex neurovascular disorder being recognized during the past two decades. It is characterized by multiple abrupt severe headaches and widespread cerebral vasoconstrictions, with potential complications such as ischemic stroke, convexity subarachnoid hemorrhage, intracerebral hemorrhage and posterior reversible encephalopathy syndrome. The clinical features, imaging findings, and dynamic disease course have been delineated. However, the pathophysiology of RCVS remains elusive. Recent studies have had substantial progress in elucidating its pathogenesis. It is now believed that dysfunction of cerebral vascular tone and impairment of blood–brain barrier may play key roles in the pathophysiology of RCVS, which explains some of the clinical and radiological manifestations of RCVS. Some other potentially important elements include genetic predisposition, sympathetic overactivity, endothelial dysfunction, and oxidative stress, although the detailed molecular mechanisms are yet to be identified. In this review, we will summarize what have been revealed in the literature and elaborate how these factors could contribute to the pathophysiology of RCVS.
A combined protein toxin screening based on the transcriptome and proteome of Solenopsis invicta
Authors: Cai Liuyang , Yang Fengling , Wang Yongfang , Yang Jishun , Zhu Yina , Ma Xueqi , Höfer Juan , Wang Yichao , Ma Yajun , Xiao Liang
Published: September 2022

Background

Multi-omics technology provides a good tool to analyze the protein toxin composition and search for the potential pathogenic factors of Solenopsis invicta, under the great harm of the accelerated invasion in southern China.

Methods

Species collection, functional annotation, toxin screening, and 3D modeling construction of three interested toxins were performed based on the successfully constructed transcriptome and proteome of S. invicta.

Results

A total of 33,231 unigenes and 721 proteins were obtained from the constructed transcriptome and proteome, of which 9,842 (29.62%) and 4,844 (14.58%) unigenes, as well as 469 (65.05%) and 71 (99.45%) proteins were annotated against the databases of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, respectively. After comparing with the uniprot toxin database, a total of 316 unigenes and 47 proteins (calglandulin, venom allergen 3, and venom prothrombin activator hopsarin-D, etc.) were successfully screened.

Conclusions

The update of annotations at the transcriptome and proteome levels presents a progression in the comprehension of S. invicta in China. We also provide a protein toxin list that could be used for further exploration of toxicity as well as its antagonistic strategy by S. invicta.
Magnitude of postpartum hemorrhage and associated factors among women who gave birth in Ethiopia: a systematic review and meta-analysis
Authors: Tolossa Tadesse , Fetensa Getahun , Zewde Edgeit Abebe , Besho Merga , Jidha Tafese Dejene
Published: September 2022

Background

Postpartum hemorrhage (PPH) is the leading cause of maternal mortality and morbidity worldwide, particularly in resource-limited countries such as Ethiopia. Findings from a few studies were inconsistent and inconclusive. Therefore, this study aimed to estimates the pooled magnitude of PPH and factors associated with PPH among women who gave birth in Ethiopia.

Methods

Electronic databases such as Medline, Pub Med, Cochrane library, the Web of Science, and Google Scholar were used to search for articles. The search period for articles was conducted from 15th August 2021 to 15th November 2021. Data were extracted using a standardized data extraction checklist and the analyses were conducted using Stata version 14. The Cochrane Q test statistic and I2 statistics were used to assessing heterogeneity. To estimate the pooled magnitude of postpartum hemorrhage, a random-effects model was fitted. Association between PPH and independent variables was reported in odds ratio (OR) with 95% confidence interval (CI). Visual assessment of publication bias was assessed using a funnel plot and Egger’s test was used to check the significant presence of publication bias.

Results

A total of 876 studies were identified from several databases and nine studies fulfilled eligibility criteria and were included in the meta-analysis. The pooled magnitude of PPH in Ethiopia was 11.14% (95% CI 7.21, 15.07). The current meta-analysis revealed that lack of antenatal care follow-up (ANC) (OR = 6.52, 95% CI 2.87, 14.81), being multipara (OR = 1.88, 95% CI 1.25, 2.85), and having the previous history of PPH (OR = 7.59, 95% CI 1.88, 30.55) were found to be significantly associated with PPH.

Conclusion

In Ethiopia the magnitude of PPH was high, and lack of ANC up follow-up, being multipara, and having a previous history of PPH were risk factors for postpartum hemorrhage. Thus, improving antenatal care follow-up is needed to decrease the magnitude of postpartum hemorrhage.
A randomised placebo-controlled trial of the effectiveness of early metformin in addition to usual care in the reduction of gestational diabetes mellitus effects (EMERGE): study protocol
Authors: Dunne F. , Newman C. , Devane D. , Smyth A. , Alvarez-Iglesias A. , Gillespie P. , Browne M. , O’Donnell M.
Published: September 2022

Background

Pregnancies affected by gestational diabetes mellitus (GDM) are associated with an increased risk of adverse maternal and foetal outcomes. Current treatments for GDM involve initial medical nutritional therapy (MNT) and exercise and pharmacotherapy in those with persistent hyperglycaemia. Insulin is considered first-line pharmacotherapy but is associated with hypoglycaemia, excessive gestational weight gain (GWG) and an increased caesarean delivery rate. Metformin is safe in selected groups of women with GDM but is not first-line therapy in many guidelines due to a lack of long-term data on efficacy. The EMERGE trial will evaluate the effectiveness of early initiation of metformin in GDM.

Methods

EMERGE is a phase III, superiority, parallel, 1:1 randomised, double-blind, placebo-controlled trial comparing the effectiveness of metformin versus placebo initiated by 28 weeks (+6 days) plus usual care.

Women aged 18–50 years will be recruited. Women with established diabetes, multiple pregnancies, known major congenital malformation or small for gestational age (<10th centile), intolerance or contraindication to the use of metformin, shock or sepsis, current gestational hypertension or pre-eclampsia, significant gastrointestinal problems, congestive heart failure, severe mental illness or galactose intolerance are excluded.

Intervention

Immediate introduction of metformin or placebo in addition to MNT and usual care. Metformin is initiated at 500mg/day and titrated to a maximum dose of 2500mg over 10 days. Women are followed up at 4 and 12 weeks post-partum to assess maternal and neonatal outcomes.

The composite primary outcome measure is initiation of insulin or fasting blood glucose ≥ 5.1 mmol/L at gestational weeks 32 or 38. The secondary outcomes are the time to insulin initiation and insulin dose required; maternal morbidity at delivery; mode and time of delivery; postpartum glucose status; insulin resistance; postpartum body mass index (BMI); gestational weight gain; infant birth weight; neonatal height and head circumference at delivery; neonatal morbidities (neonatal care unit admission, respiratory distress, jaundice, congenital anomalies, Apgar score); neonatal hypoglycaemia; cost-effectiveness; treatment acceptability and quality of life determined by the EQ5D-5L scale.

Discussion

The EMERGE trial will determine the effectiveness and safety of early and routine use of metformin in GDM.

Trial registration

EudraCT Number 2016-001644-19l; NCT NCT02980276. Registered on 6 June 2017.
Risk factors for SARS-CoV-2 transmission in student residences: a case-ascertained study
Authors: Vanbesien Marte , Molenberghs Geert , Geenen Caspar , Thibaut Jonathan , Gorissen Sarah , André Emmanuel , Raymenants Joren
Published: September 2022

Background

We aimed to investigate the overall secondary attack rates (SAR) of COVID-19 in student residences and to identify risk factors for higher transmission.

Methods

We retrospectively analysed the SAR in living units of student residences which were screened in Leuven (Belgium) following the detection of a COVID-19 case. Students were followed up in the framework of a routine testing and tracing follow-up system. We considered residence outbreaks followed up between October 30th 2020 and May 25th 2021. We used generalized estimating equations (GEE) to evaluate the impact of delay to follow-up, shared kitchen or sanitary facilities, the presence of a known external infection source and the recent occurrence of a social gathering. We used a generalized linear mixed model (GLMM) for validation.

Results

We included 165 student residences, representing 200 residence units (N screened residents = 2324). Secondary transmission occurred in 68 units which corresponded to 176 secondary cases. The overall observed SAR was 8.2%. In the GEE model, shared sanitary facilities (p = 0.04) and the recent occurrence of a social gathering (p = 0.003) were associated with a significant increase in SAR in a living unit, which was estimated at 3% (95%CI 1.5-5.2) in the absence of any risk factor and 13% (95%CI 11.4-15.8) in the presence of both. The GLMM confirmed these findings.

Conclusions

Shared sanitary facilities and the occurrence of social gatherings increase the risk of COVID-19 transmission and should be considered when screening and implementing preventive measures.
Unraveling axonal mechanisms of traumatic brain injury
Authors: Pozo Devoto Victorio M. , Lacovich Valentina , Feole Monica , Bhat Pratiksha , Chovan Jaroslav , Čarna Maria , Onyango Isaac G. , Dragišić Neda , Sűsserová Martina , Barrios-Llerena Martin E. , Stokin Gorazd B.
Published: September 2022

Axonal swellings (AS) are one of the neuropathological hallmark of axonal injury in several disorders from trauma to neurodegeneration. Current evidence proposes a role of perturbed Ca2+ homeostasis in AS formation, involving impaired axonal transport and focal distension of the axons. Mechanisms of AS formation, in particular moments following injury, however, remain unknown. Here we show that AS form independently from intra-axonal Ca2+ changes, which are required primarily for the persistence of AS in time. We further show that the majority of axonal proteins undergoing de/phosphorylation immediately following injury belong to the cytoskeleton. This correlates with an increase in the distance of the actin/spectrin periodic rings and with microtubule tracks remodeling within AS. Observed cytoskeletal rearrangements support axonal transport without major interruptions. Our results demonstrate that the earliest axonal response to injury consists in physiological adaptations of axonal structure to preserve function rather than in immediate pathological events signaling axonal destruction.
Effect of L-carnitine supplementation on lipid accumulation product and cardiovascular indices in women with overweight/obesity who have knee osteoarthritis: a randomized controlled trial
Authors: Sangouni Abbas Ali , Baghban Farnaz , Khosravi Maryam , Mozaffari-Khosravi Hassan , Dehghan Ali , Hosseinzadeh Mahdieh
Published: September 2022

Background

Osteoarthritis is associated with obesity, dyslipidemia and cardiovascular diseases. It has been hypothesized that L-carnitine can improve cardiovascular risk factors. We aimed to investigate the effect of L-carnitine supplementation on lipid accumulation product (LAP) and atherogenic indices in women with overweight/obesity who have knee osteoarthritis.

Methods

In this double-blind randomized controlled trial, seventy-six women with overweight/obesity who had knee osteoarthritis were assigned into the intervention group and control group for 12 weeks. The intervention group received 1000 mg/day L-carnitine as capsule, and the control group received placebo. The primary outcomes were LAP, atherogenic index of plasma (AIP), atherogenic coefficient (AC) and Castelli risk index II (CRI-II).

Results

We found no significant difference between the groups in baseline values of LAP, AIP, AC and CRI-II. After the intervention, a significant reduction in LAP was observed in intervention group compared to the control group (− 11.05 (− 28.24 to 0.40) vs. − 5.82 (− 24.44 to 2.68); P = 0.03). However, there was no significant difference between two groups in AIP (− 0.05 ± 0.16 vs. − 0.01 ± 0.13; P = 0.19), AC (− 0.40 ± 0.81 vs. − 0.30 ± 0.67; P = 0.67) and CRI-II (− 0.20 ± 0.76 vs. − 0.21 ± 0.47; P = 0.11).

Conclusions

L-carnitine supplementation for 12 weeks can improve LAP, but it has no effect on cardiovascular outcomes. To reach a definitive conclusion, further clinical trials with larger sample sizes and higher dosages of L-carnitine are needed.

Trial registration

Registered on 27/4/2017 at Iranian Registry of Clinical Trials IRCT2017011932026N2.
Death by late presenting of diaphragmatic hernia in an infant: case report and review of the literature
Authors: Ben Abderrahim Sarra , Jedidi Maher , Ben Daly Amal , Nfikha Zeineb , Ben Dhiab Mohamed , Zemni Majed , Mokni Moncef , Souguir Mohamed Kamel
Published: September 2022

Background

Congenital diaphragmatic hernia (CDH) is a congenital malformation of the diaphragm, resulting in the herniation of the abdominal organs into the thoracic cavity. If not properly diagnosed before or at birth, CDH represents a life-threatening pathology in infants and a major cause of death. We present a fatal case of congenital diaphragmatic hernia corresponding to Bochdalek hernia, discovered incidentally during a sudden death’s autopsy of an infant. To achieve a better view of the range of these anomalies, we also conducted a literature review on this subject describing the pathogenesis, manifestations, diagnosis, and autopsy contribution to addressing these CDH.

Case presentation

The case involved a 4-month-old female infant who presented sudden respiratory difficulties after breastfeeding. External examination found marked cyanosis with no evidence of trauma. Upon opening the chest cavity, the stomach, markedly distended, was occupying much of the left pleural cavity. The left lung was compressed and displaced superiorly, and the heart was also compressed and deviated to the right. This mediastinal deviation was due to an ascension of the stomach into the chest cavity through a 2 × 1.5 cm defect in the posterior left hemidiaphragm. Further examination remarked an ecchymotic appearance of the stomach portion entrapped in the hernia defect suggesting recent strangulation of the stomach. The lungs showed atelectasis with signs of pulmonary infection in the histology study.

Conclusions

CDH might be considered uncommon and not always mentioned in the list of sudden death in infant causes. Forensic pathologists should know of this malformation in order to apply the best autopsy techniques and thus allow positive feedback to pediatricians considering the possible legal implications.
Anti-flotillin-1/2 antibodies in a patient with neurogenic muscle atrophy and mild neuropsychological impairment
Authors: Wagner-Altendorf Tobias A. , Wandinger Klaus-Peter , Markewitz Robert , Antufjew Anna , Boppel Tobias , Münte Thomas F.
Published: September 2022

Autoimmune-mediated neural inflammation can affect both the central and the peripheral nervous system. Recently, antibodies against the peripheral membrane protein flotillin have been described in patients with multiple sclerosis, limbic encephalitis and sensorimotor demyelinating polyneuropathy. Here, we report the case of a 75-year-old male patient presenting with slowly progressive muscle weakness, as well as mild cognitive impairment. MR neurography of the leg showed fascicular enlargement and inflammation of ischiadic nerve fibers, while cerebral MRI showed bilateral hippocampal atrophy. Serological testing revealed positive anti-flotillin-1/2 antibodies in serum (1:100) and CSF (1:1). Assuming autoimmune anti-flotillin antibody-associated neurogenic muscle atrophy, the patient was treated with immunoglobulins, which led to a clinical improvement of muscle weakness. In light of the positive anti-flotillin antibodies and the local CNS immunoglobulin production, the mild cognitive impairment and hippocampal atrophy were interpreted as a cerebral involvement in the sense of a subclinical limbic encephalitis. We conclude that anti-flotillin antibodies can be associated with central and peripheral nervous system autoimmunity and should be considered in diagnostical workup.
Treatment of perianal abscess in children: spontaneous drainage or incision-drainage?
Authors: Erten Elif Emel , Öztorun Can İhsan , Ertürk Ahmet , Güney Doğuş , Bostancı Süleyman Arif , Öcal Medine Ezgi , Demir Sabri , Azılı Müjdem Nur , Şenel Emrah
Published: September 2022

Background

The aim of the study is to evaluate the clinical characteristics and compare the treatment methods for perianal abscesses by assessing our treatment experiences.

Methods

We have retrospectively analyzed the records of the children who received perianal abscess and fistula-in-ano treatment between January 2014 and January 2022. Demographic information of the patients, complaints, treatment procedures, abscess recurrence, and development of fistula-in-ano was evaluated. Patients with systemic diseases and inflammatory bowel diseases were excluded from the study.

Results

A total of 312 children (230 boys, 82 girls) were included in the study. The median age was 24.3 ± 18.1 months (1–216). In the first examination, 61 (19.5%) patients had fistula-in-ano and 25 1(80.5%) patients had a perianal abscess. The most common symptoms were erythema in the perianal region, mass, constipation, rectal bleeding, and inability to defecate. Spontaneous drainage was determined in 34.3% (n = 86) of the perianal abscess, and 65.7% (n = 165) of perianal abscesses were treated with incision-drainage without general anesthesia and systemic antibiotherapy. In the follow-up, fistula-in-ano formed in 27 patients who had a perianal abscess. Twenty-four of the patients who developed fistula-in-ano, were seen after spontaneous drainage, and 3 of them were seen after incision drainage. Perianal abscess recurred in 64 patients. Spontaneously drained abscess significantly increased the development of fistula-in-ano (p = 0.001). However, recurrences in a perianal abscess (25.4%) do not increase the fistula-in-ano formation (p > 0.05). In fistula-in-ano treatment, 10 (11.5%) patients were resolved spontaneously, 70 (79.5%) patients were treated with fistulotomy and 8 (9%) patients were treated with fistulectomy.

Conclusion

Treatment of perianal abscess and fistula-in-ano in children is still controversial. According to our results, incision-drainage and antibiotic usage in the treatment of the perianal abscess are the most appropriate treatment to decrease the rate of fistula-in-ano.
Patient Understanding of Tumor Genomic Testing: A Quality Improvement Effort
Authors: Senter Leigha , Veney Deloris , Surplus Taylor , Haynam Marcy , Adams Elizabeth J. , Hampel Heather , Toland Amanda E. , Presley Carolyn J. , Padamsee Tasleem J. , Lee Clara N. , Hovick Shelly R. , Stover Daniel G.
Published: September 2022

PURPOSE:

Tumor genomic testing (TGT) has become increasingly adopted as part of standard cancer care for many cancers. Despite national guidelines around patient education before TGT, available evidence suggests that most patients' understanding of genomics remains limited, particularly lower-income and minority patients, and most patients are not informed regarding potential incidental germline findings.

METHODS:

To investigate and address limitations in patient understanding of TGT results, a Plan-Do-Study-Act (PDSA) approach is being used to assess needs, identify opportunities for improvement, and implement approaches to optimize patient education. We reviewed published guidelines related to pre-TGT provider-patient education and to identify key points (Plan). A provider quality improvement survey was completed (Do), which highlighted inconsistency in pre-TGT discussion practice across providers and minimal discussion with patients regarding the possibility of incidental germline findings.

RESULTS:

Patient focus groups and interviews (N = 12 patients) were completed with coding of each transcript (Study), which revealed themes including trouble differentiating TGT from other forms of testing, yet understanding that results could tailor therapy. The integration of data across this initial PDSA cycle identified consistent themes and opportunities, which were incorporated into a patient-directed, concise animated video for pre-TGT education (Act), which will form the foundation of a subsequent PDSA cycle. The video addresses how TGT may/may not inform treatment, the process for TGT using existing tissue or liquid biopsy, insurance coverage, and the potential need for germline genetics follow-up because of incidental findings.

CONCLUSION:

This PDSA cycle reveals key gaps and opportunities for improvement in patient education before TGT.
Distinct Clinical Features of Post-COVID-19 Vaccination Early-onset Graves’ Disease
Authors: di Filippo Luigi , Castellino Laura , Allora Agnese , Frara Stefano , Lanzi Roberto , Perticone Francesca , Valsecchi Fanny , Vassallo Alberto , Giubbini Raffaele , Rosen Clifford J , Giustina Andrea
Published: September 2022

Context

Several case reports of Graves’ disease (GD) occurrence after COVID-19 vaccination that are possibly related to the autoimmune syndrome induced by adjuvants (ASIA) were published recently.

Objective

The aim of our study was to evaluate possible distinctive features in the presentation and clinical course of patients with GD occurring early (within 4 weeks) after COVID-19 vaccination who attended our Endocrine Unit in 2021.

Methods

Patients with a first episode of GD attending a tertiary endocrine center between January 1, 2021, and December 31, 2021, were included.

Results

Sixty-four patients with a first episode of GD were seen in 2021: 20 (31.2%) of them had onset within 4 weeks following vaccine administration. Compared with the other 44 patients, the 20 patients with postvaccine early-onset (PoVEO) GD were older (median age 51 years vs 35 years, P = .003) and more likely to be male (40.0% vs 13.6%, P = .018). At diagnosis, the biochemical and immune profiles were similar between the 2 groups. However, at 3 months after starting methimazole, patients with PoVEO GD had significantly lower thyrotropin receptor antibody titer and were taking lower doses of methimazole than the other patients with GD. None in the PoVEO group had sustained free triiodothyronine elevation.

Conclusion

This relatively large series suggests that in 2021 PoVEO GD may be a new nosologic entity representing one-third of patients evaluated for new-onset GD in our center. Distinctive features included older age at onset, higher male prevalence, and a better initial biochemical and immunologic response to treatment. Further studies are warranted to clinically and biochemically differentiate these cases from sporadically occurring GD.
Bile Acids—A Peek Into Their History and Signaling
Authors: Nguyen James T , Shaw Ryan Philip Henry , Anakk Sayeepriyadarshini
Published: September 2022

Bile acids wear many hats, including those of an emulsifier to facilitate nutrient absorption, a cholesterol metabolite, and a signaling molecule in various tissues modulating itching to metabolism and cellular functions. Bile acids are synthesized in the liver but exhibit wide-ranging effects indicating their ability to mediate organ-organ crosstalk. So, how does a steroid metabolite orchestrate such diverse functions? Despite the inherent chemical similarity, the side chain decorations alter the chemistry and biology of the different bile acid species and their preferences to bind downstream receptors distinctly. Identification of new modifications in bile acids is burgeoning, and some of it is associated with the microbiota within the intestine. Here, we provide a brief overview of the history and the various receptors that mediate bile acid signaling in addition to its crosstalk with the gut microbiota.
Deletion of Constitutive Androstane Receptor Led to Intestinal Alterations and Increased Imidacloprid in Murine Liver
Authors: Sen Anushna , Goforth Madison , Cooper Kerry K , Anakk Sayeepriyadarshini
Published: September 2022

Imidacloprid (IMI) is the most frequently detected neonicotinoid pesticide in the environment. Despite typically low toxicity in vertebrates, IMI exposure is associated with liver and gastrointestinal toxicity. The mechanism underlying IMI toxicity in mammals is unclear. Pesticide exposure frequently activates xenobiotic nuclear receptors, such as the constitutive androstane receptor (CAR), to induce detoxification phase I and phase II genes. This study examined the role of CAR in mediating IMI off-target toxicity. Female Car−/− and wild-type (WT) mice were orally administered imidacloprid (50 mg/kg, twice daily) for 21 days, following which serum, liver, and intestinal tissues were collected. Liver tissue analysis indicated mild inflammation and induction of detoxification gene Cyp2b10 in IMI-exposed WT mice. The absence of CAR increased hepatic IMI accumulation. Microbiome analysis of ileal samples revealed IMI altered microbial diversity in a genotype-specific manner, with increased α-diversity in Car−/− mice while decreased α-diversity in WT mice. We observed Car−/− mice exhibit intestinal alterations with decreased CYP-P450 expression, blunted villi height, and increased small intestine length and weight independent of IMI exposure. Our results suggest that IMI is not overtly toxic. However, the absence of xenobiotic nuclear receptor CAR allows increased accumulation of IMI in the liver and disrupts the villi structure and Cyp gene expression in the intestine.
In-Stent Stenosis After Pipeline Embolization Device in Intracranial Aneurysms: Incidence, Predictors, and Clinical Outcomes
Authors: Turhon Mirzat , Kang Huibin , Liu Jian , Zhang Yisen , Zhang Ying , Huang Jiliang , Wang Kun , Li Mengxing , Liu Jianmin , Zhang Hongqi , Li Tianxiao , Song Donglei , Zhao Yuanli , Luo Bin , Maimaiti Aierpati , Aisha Maimaitili , Wang Yunyan , Feng Wenfeng , Wang Yang , Wan Jieqing , Mao Guohua , Shi Huaizhang , Yang Xinjian , Guan Sheng
Published: September 2022

BACKGROUND:

In-stent stenosis (ISS) is a delayed complication that can occur after pipeline embolization device use when treating intracranial aneurysms (IAs).

OBJECTIVE:

To assess the incidence, predictors, and outcomes of ISS.

METHODS:

This was a retrospective, multicenter, observational study. All patient data were collected from a PLUS registry study. We collected data from patients with IA who completed digital subtraction angiography at follow-up and divided patients into “non-ISS,” “mild ISS,” or “severe ISS” groups. Multivariate logistic regression analysis was conducted to determine predictors of ISS.

RESULTS:

A total of 1171 consecutive patients with 1322 IAs participated in this study. Angiographic follow-up was available for 662 patients with 728 IAs, and the mean follow-up time was 9 months. ISS was detected in 73 cases (10.03%), including 61 mild ISS cases and 12 severe ISS cases. Univariate and multivariable analysis demonstrated that current smoking history (mild ISS: OR 2.15, 95% CI 1.122-4.118,P= .021; severe ISS: OR 5.858, 95% CI 1.186-28.93,P= .030) and cerebral atherosclerosis (mild ISS: OR 5.694, 95% CI 3.193-10.15,P= .001; severe ISS: OR 6.103, 95% CI 1.384-26.91,P= .017) were independent predictors of ISS. Compared with the other groups, the severe ISS group had higher rate of ischemic stroke (33.3%).

CONCLUSION:

ISS occurs in approximately 10.03% of cases at a mean follow-up of 9 months. Statistically, current smoking history and cerebral atherosclerosis are the main predictors of ISS. Severe ISS may be associated with higher risk of neurological ischemic events in patients with IA after pipeline embolization device implantation.
Unruly octopuses are the rule: Octopus vulgaris use multiple and individually variable strategies in an episodic-like memory task
Authors: Poncet Lisa , Desnous Coraline , Bellanger Cécile , Jozet-Alves Christelle
Published: September 2022

Episodic-like memory has mainly been studied through experimental tasks in which subjects have to remember what they ate, where and when or in which context. Seemingly quite common in mammals and corvids, episodic-like memory ability has also been demonstrated in the common cuttlefish, a cephalopod mollusc. To explore whether this ability is common to all cephalopods or whether it has emerged to face specific ecological constraints, we conducted an episodic-like memory task with seven Octopus vulgaris. Only one individual learnt the replenishing rates during training and subsequently showed episodic-like memory ability, whereas the other individuals favoured simpler foraging strategies, such as avoidance of familiarity and alternation, use of a win–stay strategy and risk sensitivity. A high variability in the use of these strategies was observed between and within individuals throughout training. As octopuses seem to live under lighter environmental pressure than cuttlefish, they may not need to rely on episodic-like memory ability to optimize foraging as cuttlefish do. These results highlight the differences in the use of complex cognitive abilities between cuttlefish and octopuses, which might be linked to different environmental and predatory constraints.
Improving the predictive power of xenograft and syngeneic anti-tumour studies using mice humanised for pathways of drug metabolism
Authors: Henderson Colin J. , McLaren Aileen W. , Kapelyukh Yury , Wolf C. Roland
Published: September 2022

Drug development is an expensive and time-consuming process, with only a small fraction of drugs gaining regulatory approval from the often many thousands of candidates identified during target validation. Once a lead compound has been identified and optimised, they are subject to intensive pre-clinical research to determine their pharmacodynamic, pharmacokinetic and toxicological properties, procedures which inevitably involve significant numbers of animals - mainly mice and rats, but also dogs and monkeys in much smaller numbers and for specific types of drug candidates. Many compounds that emerge from this process, having been shown to be safe and efficacious in pre-clinical studies, subsequently fail to replicate this outcome in clinical trials, therefore wasting time, money and, most importantly, animals.

The poor predictive power of animal models in pre-clinical studies is predominantly due to lack of efficacy or safety reasons, which in turn can be attributed mainly to the significant species differences in drug metabolism between humans and animals. To circumvent this, we have developed a complex transgenic mouse model – 8HUM - which faithfully replicates human Phase I drug metabolism (and its regulation), and which will generate more human-relevant data [REFINEMENT] from fewer animals [REDUCTION] in a pre-clinical setting and reduce attrition in the clinic.

One key area for the pre-clinical application of animals in an oncology setting – almost exclusively mice - is their use in anti-tumour studies. We now further demonstrate the utility of the 8HUM mouse using a murine melanoma cell line as a syngeneic tumour and also present an immunodeficient version 8HUM_Rag2-/- - for use in xenograft studies. These models will be of significant benefit not only to Pharma for pre-clinical drug development work, but also throughout the drug efficacy, toxicology, pharmacology, and drug metabolism communities, where fewer animals will be needed to generate more human-relevant data.
Squalomix: shark and ray genome analysis consortium and its data sharing platform
Authors: Nishimura Osamu , Rozewicki John , Yamaguchi Kazuaki , Tatsumi Kaori , Ohishi Yuta , Ohta Tazro , Yagura Masaru , Niwa Taiki , Tanegashima Chiharu , Teramura Akinori , Hirase Shotaro , Kawaguchi Akane , Tan Milton , D'Aniello Salvatore , Castro Filipe , Machado André , Koyanagi Mitsumasa , Terakita Akihisa , Misawa Ryo , Horie Masayuki , Kawasaki Junna , Asahida Takashi , Yamaguchi Atsuko , Murakumo Kiyomi , Matsumoto Rui , Irisarri Iker , Miyamoto Norio , Toyoda Atsushi , Tanaka Sho , Sakamoto Tatsuya , Semba Yasuko , Yamauchi Shinya , Yamada Kazuyuki , Nishida Kiyonori , Kiyatake Itsuki , Sato Keiichi , Hyodo Susumu , Kadota Mitsutaka , Uno Yoshinobu , Kuraku Shigehiro
Published: September 2022

The taxon Elasmobranchii (sharks and rays) contains one of the long-established evolutionary lineages of vertebrates with a tantalizing collection of species occupying critical aquatic habitats. To overcome the current limitation in molecular resources, we launched the Squalomix Consortium in 2020 to promote a genome-wide array of molecular approaches, specifically targeting shark and ray species. Among the various bottlenecks in working with elasmobranchs are their elusiveness and low fecundity as well as the large and highly repetitive genomes. Their peculiar body fluid composition has also hindered the establishment of methods to perform routine cell culturing required for their karyotyping. In the Squalomix consortium, these obstacles are expected to be solved through a combination of in-house cytological techniques including karyotyping of cultured cells, chromatin preparation for Hi-C data acquisition, and high fidelity long-read sequencing. The resources and products obtained in this consortium, including genome and transcriptome sequences, a genome browser powered by JBrowse2 to visualize sequence alignments, and comprehensive matrices of gene expression profiles for selected species are accessible through https://github.com/Squalomix/info.
Identification of prognostic biomarkers of invasive ductal carcinoma by an integrated bioinformatics approach
Authors: Marrugo-Padilla Albeiro , Márquez-Lázaro Johana , Álviz-Amador Antistio
Published: September 2022

Background: Invasive ductal carcinoma (IDC) is the most common breast cancer worldwide. Nowadays, due to IDC heterogeneity and its high capacity for metastasis, it is necessary to discover novel diagnostic and prognostic biomarkers. Thus, this study aimed to identify new prognostic genes of IDC using an integrated bioinformatics approach.

Methods: Using the Gene Expression Omnibus (GEO) database, we downloaded publicly available data of the whole-genome mRNA expression profile from the first three stages of IDC in two expression profiling datasets, GSE29044 and GSE32291; intra-group data repeatability tests were conducted using Pearson’s correlation test, and the differentially expressed genes (DEGs) were identified using the online tool GEO2R, followed by the construction of a protein‑protein interaction network (PPI-net) with the common DEGs identified in the three analyzed stages using the Search Tool for the Retrieval of Interacting Genes (STRING) database and Cytoscape software, from these PPI-net we identify the hub genes (prognostic genes).

Results: We found seven genes [WW domain-containing E3 ubiquitin-protein ligase 1 (WWP1), STIP1 homology and U-box containing protein 1 (STUB1), F-box and WD repeat domain containing 7 (FBXW7), kelch like family member 13 (KLHL13), ubiquitin-conjugating enzyme E2 Q1 (UBE2Q1), tripartite motif-containing 11 (TRIM11), and the beta-transducin repeat containing E3 ubiquitin-protein ligase (BTRC)] as potential candidates for IDC prognostic biomarkers, which were mainly enriched in the Ubiquitin-specific protease activity, cytoskeletal protein binding, and ligase activity. The role of these genes in the pathophysiology of IDC is not yet well characterized, representing a way to improve our understanding of the process of tumorigenesis and the underlying molecular events of IDC.

Conclusions: Genes identified may lead to the discovery of new prognostic targets and precise therapeutics for IDC.
Identification of qPCR reference genes suitable for normalising gene expression in the developing mouse embryo
Authors: Hildyard John C.W. , Wells Dominic J. , Piercy Richard J.
Published: September 2022

Background: Progression through mammalian embryogenesis involves many interacting cell types and multiple differentiating cell lineages. Quantitative polymerase chain reaction (qPCR) analysis of gene expression in the developing embryo is a valuable tool for deciphering these processes, but normalisation to stably-expressed reference genes is essential for such analyses. Gene expression patterns change globally and dramatically as embryonic development proceeds, rendering identification of consistently appropriate reference genes challenging.

Methods: We have investigated expression stability in mouse embryos from mid to late gestation (E11.5–E18.5), both at the whole-embryo level, and within the head and forelimb specifically, using 15 candidate reference genes ( ACTB, 18S, SDHA, GAPDH, HTATSF1, CDC40, RPL13A, CSNK2A2, AP3D1, HPRT1, CYC1, EIF4A, UBC, B2M and PAK1IP1), and four complementary algorithms (geNorm, Normfinder, Bestkeeper and deltaCt).

Results: Unexpectedly, all methods suggest that many genes within our candidate panel are acceptable references, though AP3D1, RPL13A and PAK1IP1 are the strongest performing genes overall (scoring highly in whole embryos, heads or forelimbs alone, and in all samples collectively). HPRT1 and B2M are conversely poor choices, and show strong developmental regulation. We further show that normalisation using our three highest-scoring references can reveal subtle patterns of developmental expression even in genes ostensibly ranked as acceptably stable ( CDC40, HTATSF1).

Conclusion: AP3D1, RPL13A and PAK1IP1 represent universally suitable reference genes for expression studies in the E11.5-E18.5 mouse embryo.
FEATURES OF PASSIVE SAFETY ASSESSMENT OF VEHICLES BY THE CRITERION – HUMAN INJURY IN ROAD TRAFFIC ACCIDENTS
Authors: Konovalova Tatyana V. , Litvinov Artem E. , Balaev Etibar , Senin Ivan S. , Mironova Maria P.
Published: September 2022

Road safety is influenced by a large number of factors, among the most negative factors are traffic accidents and their consequences. In road accidents, all categories of the population die and are injured, which entails a decrease in the population of the country and the level of health, life expectancy, length of the working period, and the distortion of the age pyramid. Existing methods for evaluating measures to improve passive safety do not fully allow establishing a correspondence between the characteristics of the car’s structural elements that ensure its passive safety and the severity of the consequences in an accident.

Purpose – the main criteria for evaluating the design of vehicles in the field of passive safety are determined.

Methodology: the article used mathematical and statistical methods of analysis.

Results: the most informative parameters for assessing the severity of injury to a person in an accident were determined, the elements of the vehicle interior were divided into groups of injury hazard in an accident.

Practical implications: Applied research in the field of post-accident safety of vehicles; carrying out experimental design work aimed at creating new high-tech technologies for the production of vehicle parts.
ELEMENTS OF ROAD INFRASTRUCTURE AND THEIR IMPACT ON ROAD SAFETY
Authors: Konovalova Tatyana V. , Nadiryan Sofiya L. , Izyumsky Alexander A. , Kotsurba Sofiya V.
Published: September 2022

In this article, the authors consider the issues of road infrastructure and their impact on road safety. The road network affects the risk of road accidents because it determines how road users perceive the environment. The basis for comparing a number of events in a traffic accident with categories of factors contributing to the accident.

Purpose – the measures and methods by which it is possible to achieve a safe level of roads are defined.

Methodology: the article used a full-scale experiment, statistical analysis, risk theory.

Results: the factors that increase road safety, provide a comfortable environment for drivers and pedestrians, and reduce the cost of repair and construction of highways are identified.

Practical implications: identification of the most effective and priority measures to improve highways in order to ensure safety and a comfortable environment. Research activities on the development of new approaches in the field of traffic management.
Achieving Reliable Causal Inference with Data-Mined Variables: A Random Forest Approach to the Measurement Error Problem
Authors: Yang Mochen , McFowland Edward , Burtch Gordon , Adomavicius Gediminas
Published: September 2022

Combining machine learning with econometric analysis is becoming increasingly prevalent in both research and practice. A common empirical strategy uses predictive modeling techniques to “mine” variables of interest from available data and then includes those variables into an econometric framework to estimate causal effects. However, because the predictions from machine learning models are inevitably imperfect, econometric analyses based on the predicted variables likely suffer from bias due to measurement error. We propose a novel approach to mitigate these biases, leveraging the random forest technique. We propose using random forest not just for prediction but also for generating instrumental variables for bias correction. The random forest algorithm performs best when comprised of a set of trees that are individually accurate in their predictions, yet which also make “different” mistakes, that is, have weakly correlated prediction errors. A key observation is that these properties are closely related to the relevance and exclusion requirements of valid instrumental variables. We design a data-driven procedure to select tuples of individual trees from a random forest, in which one tree serves as the endogenous covariate and the others serve as its instruments. Simulation experiments demonstrate its efficacy in mitigating estimation biases and its superior performance over alternative methods.

History: David Martens served as the senior editor for this article.

Data Ethics & Reproducibility Note: The code capsule is available on Code Ocean at https://codeocean.com/capsule/7039927/tree/v1 and in the e-Companion to this article (available at https://doi.org/10.1287/ijds.2022.0019 ).