bluuebunny/crossref_metadata_2025 huggingface dataset:
Demographics, clinical interests, and ophthalmology skills confidence of medical student volunteers and non-volunteers in an extracurricular community vision screening service-learning program
Authors: Burton Eleanor , Assi Lama , Vongsachang Hursuong , Swenor Bonnielin K. , Srikumaran Divya , Woreta Fasika A. , Johnson Thomas V.
Published: March 2022

Background

Medical school curricular hours dedicated to ophthalmology are low and declining. Extracurricular ophthalmology activities, such as participation in community vision screenings, may serve an important adjunctive role in medical school curricula. The Johns Hopkins University (JHU) Vision Screening In Our Neighborhoods (ViSION) Program is an example of a voluntary medical student-directed community service-learning program.

Methods

We used a mixed-methods cross-sectional approach, including an online survey and semi-structured interviews. JHU School of Medicine students enrolled in MD or MD/PhD programs during the 2019–2020 academic year were surveyed regarding demographics, career and service interests, involvement in ophthalmology-related activities, and confidence in their ophthalmology-related skills. Survey responses were compared between ViSION volunteers and non-volunteers using Fisher’s exact chi-square tests. Semi-structured interviews were conducted via webconference with 8 prior or current ViSION volunteers and responses analyzed using inductive thematic analysis. Data were collected when ViSION volunteers were in variable stages of their medical education and involvement with the ViSION program.

Results

A total of 118 medical students were included, representing an overall response rate of 24.6% of JHU medical students. ViSION volunteers reported greater involvement in ophthalmology-related research (42% vs. 4%,p < 0.001), intent to apply to ophthalmology residency programs (35% vs. 1%,p = 0.001), and confidence with multiple ophthalmology knowledge and clinical skill domains. In particular, ViSION volunteers were more likely to feel confident estimating cup-to-disc ratio using direct ophthalmoscopy (20% vs. 0%,p < 0.001). In open-ended survey and interview questions, most volunteers attributed at least some degree of their ophthalmology skill development and desire to pursue ophthalmology and public health careers to their ViSION experience.

Conclusions

Medical students who volunteered with a student-led community vision screening program were more likely to have a prior interest in ophthalmology than those who did not volunteer, but only 1/3 of volunteers planned to pursue a career in ophthalmology. Overall, volunteers reported higher confidence performing ophthalmology-related clinical skills, suggesting that student-led community vision screening programs may provide an important avenue for medical students to explore public health aspects of ophthalmology, while practicing ophthalmology exam skills and learning about common ophthalmic pathologies, regardless of their career intentions.
“Not yet a doctor”: medical student learning experiences and development of professional identity
Authors: Park Gyu Mi , Hong Ah Jeong
Published: March 2022

Background

To become a good doctor, developing a professional identity is as important as having the right knowledge and skills. Great attention has been given to professional identity in medical school because it plays an important role in the transition from student to doctor. Nonetheless, the necessity of acquiring a tremendous amount of knowledge and skill during medical school training does not create sufficient opportunities for students to develop their professional identities. Thus, this paper pays careful attention to how students’ learning experiences in medical school affect this development. The research questions are as follows. 1) How do medical students’ perceptions of doctors change or strengthen after entering medical school in the process of professional identity development? 2) What kinds of knowledge have medical students accumulated while attending medical school? How do their learning experiences affect professional identity development? 3) What is a doctor’s role and the career’s meaning to medical students, and what understanding does this awareness bring to their learning experiences and lives as future doctors?

Methods

In-depth semi-structured interviews were conducted with 20 Korean students in their fourth year of medical school; all had more than one year of experience in clinical settings. The students’ learning experiences and professional identity development were used to analyze the data using inductive thematic analysis.

Results

When students first entered medical school, they perceived their identities as “given to” them by society. However, various learning experiences during the medical school years affected them, causing them to think about becoming a doctor according to their own perceptions and the meaning of becoming a doctor in the profession. Although an isolated medical community and a competitive student culture hindered them from searching for their professional identities, informal learning experiences, including active interaction with patients, senior doctors, and others outside the medical community, enabled them to develop their professional identities. The medical students experienced a conflict between individual and professional values as they considered what kind of doctor they would be in the future.

Conclusions

The findings noted in this study extend the understanding of professional identity and informal learning experiences in medical school.
Establishing and evaluating physician-pharmacist collaborative clinics to manage patients with type 2 diabetes in primary hospitals in Hunan province: study protocol of a multi-site randomized controlled trial in the era of COVID-19 pandemic
Authors: Tan Sheng-Lan , Xiao Jie , Yuan Hai-Yan , Chen Lei , Wang Qing , Xiang Da-Xiong , Li Xia , Zhou Yan-Gang , Guo Yan , Huang Hai-Ying , Zhao Dan-Hui , Li Yue , Wang Li , Li Qun , Liu Juan , Xu Ping
Published: March 2022

Background

The COVID-19 pandemic has exerted an unprecedented and universal impact on global health system, resulting in noticeable challenges in traditional chronic disease care, of which diabetes was reported to be most influenced by the reduction in healthcare resources in the pandemic. China has the world’s largest diabetes population, and current diabetes management in China is unsatisfactory, particularly in rural areas. Studies in developed countries have demonstrated that physician-pharmacist collaborative clinics are efficient and cost-effective for diabetes management, but little is known if this mode could be adapted in primary hospitals in China. The aim of this proposed study is to develop and evaluate physician-pharmacist collaborative clinics to manage type 2 diabetes mellitus (T2DM) in primary hospitals in Hunan province.

Methods

A multi-site randomized controlled trial will be conducted to evaluate the effectiveness and cost-effectiveness of the physician-pharmacist collaborative clinics compared with usual care for Chinese patients with T2DM. Six primary hospitals will participate in the study, which will recruit 600 eligible patients. Patients in the intervention group will receive services from both physicians and pharmacists in the collaborative clinics, while the control group will receive usual care from physicians. Patients will be followed up at the 3rd, 6th, 9th and 12th month. Comparison between the two groups will be conducted by assessing the clinical parameters, process indicators and costs on diabetes. A satisfaction survey will also be carried out at the end of the study.

Discussion

If effective, the physician-pharmacist collaborative clinics can be adapted and used in primary hospitals of China to improve glycemic control, enhance medication adherence, decrease incidence of complications and reduce patients’ dependence on physicians. Findings from the present study are meaningful for developing evidence-based diabetes care policy in rural China, especially in the COVID-19 pandemic era.

Trial registration

Chinese Clinical Trial Registry, ChiCTR2000031839, Registered 12 April 2020.
A refined procedure for esophageal resection using a full minimally invasive approach
Authors: Ashiku Simon K. , Patel Ashish R. , Horton Brandon H. , Velotta Jeffrey , Ely Sora , Avins Andrew L.
Published: March 2022

Objective

Newer minimally invasive approaches to esophagectomy have brought substantial benefits to esophageal-cancer patients and continue to improve. We report here our experience with a streamlined procedure as part of a comprehensive perioperative-care program that provides additional advances in the continued evolution of this procedure.

Methods

All patients with primary esophageal cancer referred for resection to the Oakland Medical Center of the Kaiser-Permanente Northern California health plan who underwent this approach between January 2013 and August 2018 were included. Operative and clinical outcome variables were extracted from the electronic medical record, operating-room files, and manual chart review.

Results

142 patients underwent the new procedure and care program; 121 (85.2%) were men with mean age of 64.5 years. 127 (89.4%) were adenocarcinoma; 117 (82.4%) were clinical stage III or IVA. 115 (81.0%) required no jejunostomy. Median hospital length-of-stay was 3 days and 8 (5.6%) patients required admission to the intensive care unit. Postoperative complications occurred in 22 (15.5%) patients within 30 days of the procedure. There were no inpatient deaths; one patient (0.7%) died within 30 days following discharge and three additional deaths (2.1%) occurred through 90 days of follow-up.

Conclusions

This approach resulted in excellent clinical outcomes, including short hospital stays with limited need for the intensive care unit, few perioperative complications, and relatively few patients requiring feeding tubes on discharge. This comprehensive approach to esophagectomy is feasible and provides another clinically meaningful advance in the progress of minimally invasive esophagectomy. Further development and dissemination of this method is warranted.
Bi-allelic mutation of CTNNB1 causes a severe form of syndromic microphthalmia, persistent foetal vasculature and vitreoretinal dysplasia
Authors: Taylor Rachel L. , Soriano Carla Sanjuro , Williams Simon , Dzulova Denisa , Ashworth Jane , Hall Georgina , Gale Theodora , Lloyd I. Christopher , Inglehearn Chris F. , Toomes Carmel , Douzgou Sofia , Black Graeme C.
Published: March 2022

Background

Inherited vitreoretinopathies arise as a consequence of congenital retinal vascularisation abnormalities. They represent a phenotypically and genetically heterogeneous group of disorders that can have a major impact on vision. Several genes encoding proteins and effectors of the canonical Wnt/β-catenin pathway have been associated and precise diagnosis, although difficult, is essential for proper clinical management including syndrome specific management where appropriate. This work aimed to investigate the molecular basis of disease in a single proband born to consanguineous parents, who presented with microphthalmia, persistent foetal vasculature, posterior lens vacuoles, vitreoretinal dysplasia, microcephaly, hypotelorism and global developmental delay, and was registered severely visually impaired by 5 months of age.

Methods

Extensive genomic pre-screening, including microarray comparative genomic hybridisation and sequencing of a 114 gene panel associated with cataract and congenital ophthalmic disorders was conducted by an accredited clinical laboratory. Whole exome sequencing (WES) was undertaken on a research basis and in vitro TOPflash transcriptional reporter assay was utilised to assess the impact of the putative causal variant.

Results

In the proband, WES revealed a novel, likely pathogenic homozygous mutation in the cadherin-associated protein beta-1 gene (CTNNB1), c.884C>G; p.(Ala295Gly), which encodes a co-effector molecule of the Wnt/β-catenin pathway. The proband’s parents were shown to be heterozygous carriers but ophthalmic examination did not detect any abnormalities. Functional assessment of the missense variant demonstrated significant reduction of β-catenin activity.

Conclusions

This is the first report of a biallelic disease-causing variation in CTNNB1. We conclude that this biallelic, transcriptional inactivating mutation of CTNNB1 causes a severe, syndromic form of microphthalmia, persistent foetal vasculature and vitreoretinal dysplasia that results in serious visual loss in infancy.
Mild disease course of SARS-CoV-2 infections and mild side effects of vaccination in Pompe disease: a cohort description
Authors: Ismailova G. , Mackenbach M. J. , van den Hout J. M. P. , van der Ploeg A. T. , Brusse E. , Wagenmakers M. A. E. M.
Published: March 2022

Introduction

Patients with Glycogen Storage Disease type II (GSDII), an inheritable metabolic myopathy also known as Pompe disease, are considered to be at risk for severe COVID-19 due to a reduced respiratory function and a tendency to be overweight. However, so far little is known about the course of SARS-CoV-2 infection and side effects of COVID-19 vaccinations in patients with GSDII.

Methods

169 Dutch Pompe patients are followed at the Erasmus MC Rotterdam. During the COVID-19 pandemic patients were requested to directly inform their physicians about SARS-CoV-2 infection. Infected patients were interviewed regularly by telephone until their symptoms subsided. Furthermore, all patients eligible for vaccination on 16-7-2021 (≥ 17 years, n = 122) were asked to complete a questionnaire.

Results

To date, fifteen patients (8.9% of our cohort) reported a SARS-CoV-2 infection (classic infantile Pompe disease n = 5, late onset n = 10). No patients were admitted to hospital or needed intensivation of ventilatory support. All patients made a recovery within 19 days. 41.8% of patients filled in our questionnaire regarding vaccination, of whom 98% were vaccinated. Besides one case of perimyocarditis, only mild side effects were reported.

Conclusion

Overall, patients with Pompe disease showed mild symptoms from infection with SARS-CoV-2. All patients made a full recovery. Side effects after vaccination were mostly mild.
Activity of putative orexin neurons during cataplexy
Authors: Zhou Shi , Yamashita Akira , Su Jingyang , Zhang Yang , Wang Wuyang , Hao Liying , Yamanaka Akihiro , Kuwaki Tomoyuki
Published: March 2022

It is unclear why orexin-deficient animals, but not wild-type mice, show cataplexy. The current hypothesis predicts simultaneous excitation of cataplexy-inhibiting orexin neurons and cataplexy-inducing amygdala neurons. To test this hypothesis, we measured the activity of putative orexin neurons in orexin-knockout mice during cataplexy episodes using fiber photometry. We created two animal models of orexin-knockout mice with a GCaMP6 fluorescent indicator expressed in putative orexin neurons. We first prepared orexin-knockout mice crossed with transgenic mice carrying a tetracycline-controlled transactivator transgene under the control of the orexin promoter. TetO-GCaMP6 was then introduced into mice via an adeno-associated virus injection or natural crossing. The resulting two models showed restricted expression of GCaMP6 in the hypothalamus, where orexin neurons should be located, and showed excitation to an intruder stress that was similar to that observed in orexin-intact mice in our previous study. The activity of these putative orexin neurons increased immediately before the onset of cataplexy-like behavior but decreased (approximately − 20% of the baseline) during the cataplexy-like episode. We propose that the activity of orexin neurons during cataplexy is moderately inhibited by an unknown mechanism. The absence of cataplexy in wild-type mice may be explained by basal or residual activity-induced orexin release, and emotional stimulus-induced counter activation of orexin neurons may not be necessary. This study will serve as a basis for better treatment of cataplexy in narcolepsy patients.
Spatiotemporal parameters and gait variability in people with psoriatic arthritis (PsA): a cross‐sectional study
Authors: Walha Roua , Gaudreault Nathaly , Dagenais Pierre , Boissy Patrick
Published: March 2022

Background

Foot involvement is a major manifestation of psoriatic arthritis (PsA) and can lead to severe levels of foot pain and disability and impaired functional mobility and quality of life. Gait spatiotemporal parameters (STPs) and gait variability, used as a clinical index of gait stability, have been associated with several adverse health outcomes, including risk of falling, functional decline, and mortality in a wide range of populations. Previous studies showed some alterations in STPs in people with PsA. However, gait variability and the relationships between STPs, gait variability and self‐reported foot pain and disability have never been studied in these populations. Body‐worn inertial measurement units (IMUs) are gaining interest in measuring gait parameters in clinical settings.

Objectives

To assess STPs and gait variability in people with PsA using IMUs, to explore their relationship with self‐reported foot pain and function and to investigate the feasibility of using IMUs to discriminate patient groups based on gait speed‐critical values.

Methods

Twenty‐one participants with PsA (age: 53.9 ± 8.9 yrs.; median disease duration: 6 yrs) and 21 age‐ and sex‐matched healthy participants (age 54.23 ± 9.3 yrs) were recruited. All the participants performed three 10‐m walk test trials at their comfortable speed. STPs and gait variability were recorded and calculated using six body‐worn IMUs and Mobility Lab software (APDM®). Foot pain and disability were assessed in participants with PsA using the foot function index (FFI).

Results

Cadence, gait speed, stride length, and swing phase were significantly lower, while double support was significantly higher, in the PsA group (p < 0.006). Strong correlations between STPs and the FFI total score were demonstrated (|r| > 0.57, p < 0.006). Gait variability was significantly increased in the PsA group, but it was not correlated with foot pain or function (p < 0.006). Using the IMUs, three subgroups of participants with PsA with clinically meaningful differences in self‐reported foot pain and disability were discriminated.

Conclusion

STPs were significantly altered in participants with PsA, which could be associated with self‐reported foot pain and disability. Future studies are required to confirm the increased gait variability highlighted in this study and its potential underlying causes. Using IMUs has been useful to objectively assess foot function in people with PsA.

Trial registration

ClinicalTrials.gov, NCT05075343, Retrospectively registered on 29 September 2021.
miR-4324 inhibits ovarian cancer progression by targeting FEN1
Authors: Wu Haixia , Yan Youliang , Yuan Jialin , Luo Mengze , Wang Yingjian
Published: March 2022

Background

Ovarian cancer is one of the most lethal malignancies, with a 1.9% mortality rate worldwide. The dysregulation of the FEN1 gene and miR-4324 has been associated with cancer progression. However, the relationship between miR-4324 and-FEN1 requires further investigation.

Methods

miR-4324 and FEN1 expressions in ovarian cancer tissues and cell lines were measured via RT-qPCR. The interaction between miR-4324 and FEN1 was assessed using luciferase and RNA pull-down assays. The effects of miR-4324 and FEN1 on cell proliferation, adhesion and apoptosis were determined by CCK-8, BrdU, colony formation, cell adhesion, Caspase-3 and western blot assays in ovarian cancer cell lines CaOV3 and OVCAR3, respectively.

Results

The results showed that miR-4324 expression was significantly decreased and FEN1 expression was enhanced in ovarian cancer tissues and cell lines. miR-4324 inhibitor promoted cell proliferation, adhesion and migration, and prevented apoptosis. Furthermore, the downregulation of FEN1 inhibited ovarian cancer cell growth and increased apoptosis. miR-4324 inhibited FEN1 expression and repressed ovarian cancer progression.

Conclusion

Our study found that miR-4324 inhibited FEN1 expression, suppressed cell growth, and increased apoptosis in ovarian cancer cells. Therefore, we identified miR-4324 and FEN1 as potential therapeutic targets for ovarian cancer treatment.
Hospital management of hyperglycemia in the context of COVID-19: evidence-based clinical considerations
Authors: Mendes Thiago Bosco , Câmara-de-Souza Alexandre Barbosa , Halpern Bruno
Published: March 2022

The COVID-19 pandemic led to an unprecedented crisis, and early on, it has been shown that diabetes is an important risk factor for complications and mortality in infected patients, as demonstrated by several studies. Moreover, hyperglycemia, regardless of whether patients have diabetes, is associated with poorer outcomes, which suggests that adequate monitoring and treatment of elevated glycemia in the hospital setting can improve patient outcomes. In patients with COVID-19, glycemic control may be impaired as a consequence of the infection itself (aggravating pre-existing diabetes and potentially precipitating new-onset diabetes), inflammation, or corticosteroid use—a well-established therapy to reduce COVID-19 complications, especially in the intensive care unit. This article reviews the link between diabetes and hyperglycemia, and COVID-19, with a brief review of potential mechanisms, along with emerging evidence on the effect of glycemic control on COVID-19 outcomes, especially in hospital settings.
Unexpected benefits of and lessons learned from shifting to virtual focus group discussions in the BEECON trial
Authors: Lindau Helen , Ramos-Gomez Francisco , Garza Jeremiah , Finlayson Tracy , Pareja Morgan , Liu Jenny , Gansky Stuart
Published: March 2022

Objective

The COVID-19 pandemic has forced many human subjects research to halt in-person activities and pivot to virtual engagement, including Focus Groups (FGs). We highlight learnings from our experience of hosting virtual FGs from our BEhavioral EConomics for Oral health iNnovation (BEECON) study focusing on oral hygiene behaviors among low-income, predominantly Hispanic families, including practical tips and potential pitfalls to avoid for researchers considering virtual engagement.

Results

There can be particular benefits to holding virtual sessions among minority parents of young children—to provide flexibility, comfort, and reduced logistical barriers for participation—while still facilitating friendly conversation with minimal distractions. However, extensive preparation is needed to ensure smooth execution and minimal distractions.
Accurate categorisation of menopausal status for research studies: a step-by-step guide and detailed algorithm considering age, self-reported menopause and factors potentially masking the occurrence of menopause
Authors: Yap Sarsha , Vassallo Amy , Goldsbury David E. , Salagame Usha , Velentzis Louiza , Banks Emily , O’Connell Dianne L. , Canfell Karen , Steinberg Julia
Published: March 2022

Objective

Menopausal status impacts risk for many health outcomes. However, factors including hysterectomy without oophorectomy and Menopausal Hormone Therapy (MHT) can mask menopause, affecting reliability of self-reported menopausal status in surveys. We describe a step-by-step algorithm for classifying menopausal status using: directly self-reported menopausal status; MHT use; hysterectomy; oophorectomy; intervention timing; and attained age. We illustrate this approach using the Australian 45 and Up Study cohort (142,973 women aged ≥ 45 years).

Results

We derived a detailed seven-category menopausal status, able to be further consolidated into four categories (“pre-menopause”/“peri-menopause”/“post-menopause”/“unknown”) accounting for participants’ ages. 48.3% of women had potentially menopause-masking interventions. Overall, 93,107 (65.1%), 9076 (6.4%), 17,930 (12.5%) and 22,860 (16.0%) women had a directly self-reported “post-menopause”, “peri-menopause”, “pre-menopause” and “not sure”/missing status, respectively. 61,464 women with directly self-reported “post-menopause” status were assigned a “natural menopause” detailed derived status (menopause without MHT use/hysterectomy/oophorectomy). By accounting for participants’ ages, 105,817 (74.0%) women were assigned a “post-menopause” consolidated derived status, including 15,009 of 22,860 women with “not sure”/missing directly self-reported status. Conversely, 3178 of women with directly self-reported “post-menopause” status were assigned “unknown” consolidated derived status. This algorithm is likely to improve the accuracy and reliability of studies examining outcomes impacted by menopausal status.
Roles for the methyltransferase SETD8 in DNA damage repair
Authors: Xu Libo , Zhang Ling , Sun Jicheng , Hu Xindan , Kalvakolanu Dhan V. , Ren Hui , Guo Baofeng
Published: March 2022

Epigenetic posttranslational modifications are critical for fine-tuning gene expression in various biological processes. SETD8 is so far the only known lysyl methyltransferase in mammalian cells to produce mono-methylation of histone H4 at lysine 20 (H4K20me1), a prerequisite for di- and tri-methylation. Importantly, SETD8 is related to a number of cellular activities, impinging upon tissue development, senescence and tumorigenesis. The double-strand breaks (DSBs) are cytotoxic DNA damages with deleterious consequences, such as genomic instability and cancer origin, if unrepaired. The homology-directed repair and canonical nonhomologous end-joining are two most prominent DSB repair pathways evolved to eliminate such aberrations. Emerging evidence implies that SETD8 and its corresponding H4K20 methylation are relevant to establishment of DSB repair pathway choice. Understanding how SETD8 functions in DSB repair pathway choice will shed light on the molecular basis of SETD8-deficiency related disorders and will be valuable for the development of new treatments. In this review, we discuss the progress made to date in roles for the lysine mono-methyltransferase SETD8 in DNA damage repair and its therapeutic relevance, in particular illuminating its involvement in establishment of DSB repair pathway choice, which is crucial for the timely elimination of DSBs.
DWI-based radiomic signature: potential role for individualized adjuvant chemotherapy in intrahepatic cholangiocarcinoma after partial hepatectomy
Authors: Yang Yang , Zou Xianlun , Zhou Wei , Yuan Guanjie , Hu Daoyu , Shen Yaqi , Xie Qingguo , Zhang Qingpeng , Kuang Dong , Hu Xuemei , Li Zhen
Published: March 2022

Objectives

To develop a diffusion-weighted imaging (DWI) based radiomic signature for predicting early recurrence (ER) (i.e., recurrence within 1 year after surgery), and to explore the potential value for individualized adjuvant chemotherapy.

Methods

A total of 124 patients with intrahepatic cholangiocarcinoma (ICC) were randomly divided into the training (n = 87) and the validation set (n = 37). Radiomic signature was built using radiomic features extracted from DWI with random forest. An integrated radiomic nomogram was constructed with multivariate logistic regression analysis to demonstrate the incremental value of the radiomic signature beyond clinicopathological-radiographic factors. A clinicopathological-radiographic (CPR) model was constructed as a reference.

Results

The radiomic signature showed a comparable discrimination performance for predicting ER to CPR model in the validation set (AUC, 0.753 vs. 0.621, p = 0.274). Integrating the radiomic signature with clinicopathological-radiographic factors further improved prediction performance compared with CPR model, with an AUC of 0.821 (95%CI 0.684–0.959) in the validation set (p = 0.01). The radiomic signature succeeded to stratify patients into distinct survival outcomes according to their risk index of ER, and remained an independent prognostic factor in multivariable analysis (disease-free survival (DFS), p < 0.0001; overall survival (OS), p = 0.029). Furthermore, adjuvant chemotherapy improved prognosis in high-risk patients defined by the radiomic signature (DFS, p = 0.029; OS, p = 0.088) and defined by the nomogram (DFS, p = 0.031; OS, p = 0.023), whereas poor chemotherapy efficacy was detected in low-risk patients.

Conclusions

The preoperative DWI-based radiomic signature could improve prognostic prediction and help to identify ICC patients who may benefit from postoperative adjuvant chemotherapy.
A novel missense mutation in complement factor I predisposes patients to atypical hemolytic uremic syndrome: a case report
Authors: Wei Xin , Li Juan , Zhan Xiaojiang , Tu Luxia , Huang Haowen , Wang Ying
Published: March 2022

Background

Atypical hemolytic uremic syndrome, also called the nondiarrheal form of hemolytic uremic syndrome, is a rare disease characterized by the triad of thrombocytopenia, Coomb’s test-negative microangiopathic hemolytic anemia, and acute renal failure. Approximately 60% of cases of atypical hemolytic uremic syndrome are associated with deficiencies of the complement regulatory protein, including mutations in complement factor H, complement factor I, or the membrane co-factor protein.

Case presentation

We report the case of a 26-year-old Asian man who presented with pulmonary infection, elevated blood pressure, microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Renal biopsy revealed diffuse capillary fibrin deposition, endothelial swelling, and arteriole narrowing like “onion skinning” consistent with thrombotic microangiopathy. Bidirectional sequencing of CFH, CFHR5, CFHR1, CFI, DGKE, CFB, and MCP confirmed that the patient was heterozygous for a novel missense mutation, p.Cys67Phe, in CFI. This patient had rapid evolution to end-stage renal disease and needed renal replacement therapy. Plasma exchange seemed inefficacious in this patient.

Conclusions

This report confirms the importance of screening patients with atypical hemolytic uremic syndrome for mutations in genes involved in complement system to clarify the diagnosis and demonstrates the challenges in the management of these patients.
Scedosporium apiospermium keratitis: a case report
Authors: Karaca Umut
Published: March 2022

Background

Scedosporium apiospermum, an opportunistic and filamentous fungus, is a rarely seen ocular entity that is difficult to identify and heal. We report a challenging case of S. apiospermium keratitis and discuss the treatment modalities in light of previous studies.

Case presentation

A 30-year-old Turkish farmer with a history of contact lens misuse presented to our clinic with a painful corneal abscess and severe vision loss in his left eye. S. apiospermum was identified by spectrophotometric analysis. The patient was successfully treated with therapeutic penetrating keratoplasty, but was resistant to fluconazole and amphotericin B and susceptible but unresponsive to voriconazole.

Conclusion

S. apiospermum keratitis should be considered in the differential diagnosis of immunocompromised and immunocompetent patients with history of ocular trauma and contact lens use, especially those who do not respond to treatment.
Intensive care unit capacity and mortality in older adults: a three nations retrospective observational cohort study
Authors: Abuhasira Ran , Anstey Matthew , Novack Victor , Bose Somnath , Talmor Daniel , Fuchs Lior
Published: March 2022

Background

Intensive care unit (ICU) admissions among older adults are expected to increase, while the benefit remains uncertain. The availability of ICU beds varies between hospitals and between countries and is an important factor in the decision to admit older adults in the ICU. We aimed to assess if a non-restrictive approach to ICU older adults admission is associated with a corresponding change in survival.

Methods

Retrospective cohort study that included patients ≥ 80 years who were admitted to each of the three participating hospitals in Australia, Israel, and the United States (USA), between the years 2006–2015, each with distinct ICU capacities and admission criteria. The primary outcomes were in-hospital mortality and all-cause mortality at 6, 12, 18, and 24 months following index hospitalization.

Results

The cohort included 62,866 patients with a mean age of 85.9 ± 4.6 years and 58.8% were women. The ICU admission rates were 22.5%, 2.6% and 2.3% in USA, Australia, and Israel, respectively. We constructed a model for ICU admissions based on the USA cohort (highest availability of ICU beds) and then calculated the expected probabilities for the Israeli and Australian cohorts. For the patients in the highest quintile of the admission model, actual ICU admission rates were 67.6% in USA, 22.1% in Australia and 6.0% in Israel. Of these, in-hospital death rates were 52.3% in Israel, 29.8% in Australia, and 22.1% in USA. Two years after hospital discharge, the survival rates in the USA and Australia were 53%, while in Israel 48%.

Conclusion

ICU admission of adults ≥ 80 years is associated with increased in-hospital survival compared to ward admission, but survival rates 2 years later are similar.
Intracranial otogenic complications in adults: New factors that influenced its onset, frequency and nature
Authors: Wierzbicka Małgorzata , Staśkiewicz Michalina , Rosiak Oskar , Karmelita-Katulska Katarzyna , Szyfter Witold , Gawęcki Wojciech
Published: March 2022

Background

To compare the clinical features of two time cohorts of patients: “pre-COVID-19” and “COVID-19”—admitted as emergency with intracranial otogenic complications, with special regard to sigmoid sinus thrombosis (CVST).

Methods

Retrospective analysis of patients documentation concerning urgent procedures of intracranial otogenic complications at tertiary-referral otolaryngology department. Analysed database—pre-COVID-19 cohort (January–February 2019/2020): 1434 otological outpatient visits, 509 planned otosurgeries and 17 urgent otological procedures; COVID-19 cohort (March–April 2020/2021): 1150, 566 and 20 respectively. Overall intracranial complications: 5 and 9 respectively. Analysed outcome measures: incidence proportion of otogenic intracranial complications in relation to planned and urgent otosurgical procedures; incidence proportion of intracranial complications in relation to the total number of emergency and planned outpatient consultations and the total number of planned surgical procedures.

Results

There were 14 intracranial complications, 5 in the pre-COVID and 9 in the COVID cohort, including 1 and 5 sigmoid sinus thrombosis, respectively. Out of them, 3 and 5 patients reported a prior history of chronic otitis media, respectively. In COVID period, CVST was more prevalent, with 2 cases (22.2%) presenting solitary CVST, and 3 cases (33.3%) CVST and a simultaneous brain abscess or meningitis. CVST was much more frequent in the COVID period (p < 0.01).

Conclusions

Despite the published data which suggest that CVST is a rare event associated with COVID-19 infection, based on our experience, CVST can be expected as a frequent component of intracranial otogenic complications during COVID-19 pandemic time. Trial registration This research study was conducted retrospectively from data obtained for clinical purposes. We consulted extensively with the Bioethics Committee at Poznan University of Medical Sciences who determined that our study did not need ethical approval. An official waiver of ethical approval was granted from the Bioethics Committee at Poznan University of Medical Sciences.

Graphical Abstract
Rapid prototyping for series of tasks in atypical environment: robotic system with reliable program-based and flexible learning-based approaches
Authors: Ito Hiroshi , Nakamura Satoshi
Published: March 2022

We propose a novel robotic system that combines both a reliable programming-based approach and a highly generalizable learning-based approach. How to design and implement a series of tasks in an atypical environment is a challenging issue. If all tasks are implemented using a programming-based approach, the development costs will be huge. However, if a learning-based approach is used, reliability is an issue. In this paper, we propose novel design guidelines that focus on the respective advantages of programming-based and learning-based approaches and select them so that they complement each other. We use a program-based approach for motions that is rough behavior and a learning-based approach for motion that is required complex interaction between robot and object of robot tasks and are difficult to achieve with a program. Our learning approach can easily and rapidly accomplish a series of tasks consisting of various motions because it does not require a computational model of an object to be designed in advance. We demonstrate a series of tasks in which randomly arranged parts are assembled using an actual robot.
Internal Training Load Perceived by Athletes and Planned by Coaches: A Systematic Review and Meta-Analysis
Authors: Inoue Allan , dos Santos Bunn Priscila , do Carmo Everton Crivoi , Lattari Eduardo , da Silva Elirez Bezerra
Published: March 2022

Background

Rating of perceived exertion (RPE) and session RPE (sRPE) has been widely used to verify the internal load in athletes. Understanding the agreement between the training load prescribed by coaches and that perceived by athletes is a topic of great interest in sport science.

Objective

This systematic review and meta-analysis aimed to investigate differences between the training/competition load perceived by athletes and prescribed/intended/observed by coaches.

Methods

A literature search (September 2020 and updated in November 2021) was conducted using PubMed, Web of Science, Embase, and SPORTDiscus databases. The protocol was registered in the Open Science Framework (osf.io/wna4x). Studies should include athletes and coaches of any sex, age, or level of experience. The studies should present outcomes related to the RPE or sRPE for any scale considering overall training/competition sessions (physical, strength, tactical, technical, games) and/or classified into three effort categories: easy, moderate, and hard.

Results

Twenty-seven studies were included in the meta-analysis. No difference was found between coaches and athletes for overall RPE (SMD = 0.19, P = 0.10) and overall sRPE (SMD = 0.05, P = 0.75). There was a difference for easy RPE (SMD = − 0.44, small effect size, P = 0.04) and easy sRPE (SMD = − 0.54, moderate effect size, P = 0.04). No differences were found for moderate RPE (SMD = 0.05, P = 0.74) and hard RPE (SMD = 0.41, P = 0.18). No difference was found for moderate (SMD = -0.15, P = 0.56) and hard (SMD = 0.20, P = 0.43) sRPE.

Conclusion

There is an agreement between coaches and athletes about overall RPE and sRPE, and RPE and sRPE into two effort categories (moderate and hard). However, there were disagreements in RPE and sRPE for easy effort category. Thus, despite a small disagreement, the use of these tools seems to be adequate for training monitoring.
Rapid detection of single nucleotide polymorphisms using the MinION nanopore sequencer: a feasibility study for perioperative precision medicine
Authors: Tabata Yoshiteru , Matsuo Yoshiyuki , Fujii Yosuke , Ohta Atsufumi , Hirota Kiichi
Published: March 2022

Introduction

Precision medicine is a phrase used to describe personalized medical care tailored to specific patients based on their clinical presentation and genetic makeup. However, despite the fact that several single nucleotide polymorphisms (SNPs) have been reported to be associated with increased susceptibility to particular anesthetic agents and the occurrence of perioperative complications, genomic profiling and thus precision medicine has not been widely applied in perioperative management.

Methods

We validated six SNP loci known to affect perioperative outcomes in Japanese patients using genomic DNA from saliva specimens and nanopore sequencing of each SNP loci to facilitate allele frequency calculations and then compared the nanopore results to those produced using the conventional dideoxy sequencing method.

Results

Nanopore sequencing reads clustered into the expected genotypes in both homozygous and heterozygous cases. In addition, the nanopore sequencing results were consistent with those obtained using conventional dideoxy sequencing and the workflow provided reliable allele frequency estimation, with a total analysis time of less than 4 h.

Conclusion

Thus, our results suggest that nanopore sequencing is a promising and versatile tool for SNP genotyping, allowing for rapid and feasible risk prediction of perioperative outcomes.
LPAR2 correlated with different prognosis and immune cell infiltration in head and neck squamous cell carcinoma and kidney renal clear cell carcinoma
Authors: Sun Kai , Chen Ri-xin , Li Jing-zhang , Luo Zhan-xiong
Published: March 2022

Background

Lysophosphatidic acid (LPA) and its receptors play a key role in regulating cancer progression. Upregulation of LPA receptor 2 (LPAR2) plays a role in carcinogenesis; however, the exact role of LPAR2 in tumors remains elusive. This study aims to explore the correlation between LPAR2 expression with tumor prognosis and immune infiltration in pan-cancers.

Materials and methods

The expression of LPAR2 in pan-cancers was analyzed using the Online Cancer Microarray Database (Oncomine), Tumor Immune Estimation Resource (TIMER), and UALCAN databases. The effects of LPAR2 on the clinical prognosis in pan-cancer were examined using the Kaplan–Meier plotter (KM plotter) as well as Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, and Human Protein Atlas (HPA) databases. Moreover, the R software program was applied for validation of expression and prognostic value of LPAR2 in tumor patients in the Cancer Genome Atlas (TCGA) dataset and the Gene Expression Omnibus (GEO) database. The relationship between the expression level of LPAR2 and the clinical and molecular criteria of head and neck squamous cell carcinoma (HNSC) and kidney renal clear cell carcinoma (KIRC) was analyzed using UALCAN, whereas the relationship between LPAR2 expression and prognosis in patients with HNSC and KIRC with different clinical characteristics was examined using the KM plotter. Furthermore, the correlation between LPAR2 expression and tumor immune infiltration was examined using TIMER. The correlation between LPAR2 expression and gene markers of tumor immune infiltrates was analyzed using TIMER and GEPIA. In addition, the cBioPortal for Cancer Genomics was used to calculate the mutations, methylations, and altered neighbor genes of LPAR2.

Results

The expression of LPAR2 was significantly correlated with the outcome of multiple types of cancer, especially HNSC and KIRC. Furthermore, high expression of LPAR2 was significantly associated with various immune markers in the immune cell subsets of HNSC and KIRC.

Conclusions

High expression of LPAR2 plays significantly different prognostic roles in HNSC and KIRC possibly owing to its association with different immune markers. LPAR2 is correlated with tumor immune cell infiltration and is a valuable prognostic biomarker for HNSC and KIRC. However, further experiments are required to validate these findings.
Interaction of prior category knowledge and novel statistical patterns during visual search for real-world objects
Authors: Moon Austin , Zhao Jiaying , Peters Megan A. K. , Wu Rachel
Published: March 2022

Two aspects of real-world visual search are typically studied in parallel: category knowledge (e.g., searching for food) and visual patterns (e.g., predicting an upcoming street sign from prior street signs). Previous visual search studies have shown that prior category knowledge hinders search when targets and distractors are from the same category. Other studies have shown that task-irrelevant patterns of non-target objects can enhance search when targets appear in locations that previously contained these irrelevant patterns. Combining EEG (N2pc ERP component, a neural marker of target selection) and behavioral measures, the present study investigated how search efficiency is simultaneously affected by prior knowledge of real-world objects (food and toys) and irrelevant visual patterns (sequences of runic symbols) within the same paradigm. We did not observe behavioral differences between locating items in patterned versus random locations. However, the N2pc components emerged sooner when search items appeared in the patterned location, compared to the random location, with a stronger effect when search items were targets, as opposed to non-targets categorically related to the target. A multivariate pattern analysis revealed that neural responses during search trials in the same time window reflected where the visual patterns appeared. Our finding contributes to our understanding of how knowledge acquired prior to the search task (e.g., category knowledge) interacts with new content within the search task.
Association of inflammatory biomarker abnormalities with mortality in COVID-19: a meta-analysis
Authors: Suri Arpita , Singh Naveen Kumar , Perumal Vanamail
Published: March 2022

Background

COVID-19 outbreak has engulfed different parts of the world, affecting more than 163 million people and causing more than 3 million deaths worldwide due to human transmission. Thus, it has become critical to identify the risk factors and laboratory parameters to identify patients who have high chances of worsening clinical symptoms or poor clinical outcomes. Therefore, the study aims to identify inflammatory markers that can help identify patients at increased risk for progression to critical illness, thus decreasing the risk of any mortality. Our study focussed on the predictive utility of C-reactive protein, Interleukin-6, D-dimer and Procalcitonin in assisting the management of COVID-19 patients with adverse clinical effects. Through literature search in electronic databases, we included the retrospective studies that evaluated the biomarkers among confirmed COVID-19 patients before initiation of treatment and who had a definite outcome (dead or discharged). Biomarkers were expressed in standardized difference in mean value, calculated based on study sizes and mean values between survivors and non-survivors considered the effect size. We carried out a meta-regression analysis to identify the causes of the heterogeneity between the studies.

Results

Number of studies eligible for C-reactive protein, D-dimer and Interleukin-6 markers were eight, seven and four, respectively. Using random effect model revealed that the overall effect size with 95% confidence interval (CI) for C-reactive protein, D-dimer and Interleukin-6 were 1.45 (0.79–2.12) milligrams/litre, 1.12 (0.64–1.59) micrograms/millilitre Fibrinogen Equivalent Units and 1.34 (0.43–2.24) picograms/millilitre respectively was statistically significant (P < 0.05) inferring that the mean scores of these marker were significantly higher among the non-survivors compared to the survivors. Two studies were eligible for Procalcitonin marker and there was no heterogeniety (I2-statistics = 0) between these studies. Therefore, fixed-effect model revealed that the overall effect size (95% CI) for Procalcitonin was 0.75 (0.30–1.21) Nanograms/millilitre was also high among non-survivors.

Conclusions

The study found that serum levels of C-reactive protein, Interleukin-6 and D-dimer showed significant elevation in non-survivors compared to survivors. Raised inflammatory markers aid in the risk stratification of COVID-19 patients and their proper management.