bluuebunny/crossref_metadata_2025 huggingface dataset:
Female Representation Among CORE Grant Recipients by Research Subspeciality
Authors: Roman Kelsey M. , Bui Anh‐Tram , Birkenbeuel Jack , Tjoa Tjoson , Haidar Yarah M. , Kuan Edward C.
Published: February 2022

This study evaluates the gender distribution of Centralized Otolaryngology Research Efforts (CORE) grants by research subspeciality over the past decade. Demographic information on CORE grant recipients from 2010 to 2019 was extracted through an Internet search, and research projects were categorized by subspeciality. Of 343 grants awarded during this period, 127 (37%) were awarded to women. Analysis demonstrated lower absolute rates of CORE funding for women in all fields except pediatrics, but women receive a proportional number of grants for most subspecialities based on their representation within the field.
Hearing Stability in Patients With Unilateral Hearing Loss Due to Congenital CMV
Authors: Tissera Kristin A. , Williams Alisha , Perry Julia , Kawai Kosuke , Kenna Margaret , Mankarious Leila A.
Published: February 2022

Objective

To determine the incidence and severity of progressive hearing loss in both ears in a population of longitudinally‐tracked patients with unilateral hearing loss due to congenital cytomegalovirus (cCMV). By determining the natural history of unilateral hearing loss due to cCMV infection, we aim to facilitate therapeutic recommendations.

Study Design

Retrospective chart review.

Setting

Two tertiary care hospitals.

Methods

Pure‐tone averages (PTAs) based on yearly audiograms were calculated for each patient for both ears, and changes were assessed using a linear mixed‐effects model.

Results

A total of 32 patients with cCMV with congenital, unilateral hearing loss were enrolled. Of these, 4 (12.5%) had progressive losses ≥10 dB by PTA in the initially normal‐hearing ear. For the hearing‐impaired side, the mean (SD) PTA at initial presentation was 67.9 (29.2) dB. Eight patients initially in this cohort had profound hearing impairment, and of the other 24 patients, 17 (70.8%) had hearing loss progression. Hearing levels stabilized in the initially normal‐hearing and hearing‐impaired ear when patients were approximately 10 and 2 years old, respectively.

Conclusion

In 32 patients with unilateral hearing loss related to cCMV, 4 (12.5%) exhibited a shift in hearing levels in the normal‐hearing ear that progressively stabilized by age 10 years. For ears with congenital hearing loss, progressive stabilization of hearing occurred by age 2 years.
Patient Satisfaction With Otolaryngology Care: Stratification by Race, Age, Gender, Income, and Language
Authors: Naunheim Matthew R. , Xu Lucy , Zhou Guohai , Agarwala Aalok
Published: February 2022

Objective

To understand how race, gender, income, and language are correlated with patient satisfaction scores.

Study Design

Cross‐sectional analysis of patient satisfaction data.

Setting

An urban/suburban academic otolaryngology practice.

Methods

Patients presenting for outpatient otolaryngology visits from 2017 to 2020 were surveyed for patient satisfaction following a visit with their otolaryngology provider. Categorical responses and numerical responses were collected regarding overall satisfaction as well as a variety of more specific satisfaction questions. Responses were matched to both provider characteristics and patient demographic data. Differences in satisfaction by demographic data were assessed with descriptive statistics as well as a multivariable mixed‐effect model to adjust for repeated responder data and control for confounding factors.

Results

In total, 55,469 surveys were included, the majority of which were from white, English‐speaking patients. Overall satisfaction levels were very high across all questions. The individual provider was associated highly with satisfaction, but provider gender was not. Race, age, and gender of the patient had a statistically significant impact on patient satisfaction, with higher levels of satisfaction among patients who were older, white, and male; income and language did not.

Conclusion

Patient factors including race, age, and gender had a significant impact on ratings on outpatient otolaryngology patient satisfaction surveys, with nonwhite, younger, female patients reporting lower scores.
Hurdles in Diversifying Otolaryngology: A Survey of Medical Students
Authors: Johnson Bria C. , Hayden Jamil , Jackson Jarrett , Harley Randall , Harley Earl H.
Published: February 2022

The field of otolaryngology has one of the lowest rates of racial and ethnic diversity. An anonymous survey was distributed to members of the Student National Medical Association at different medical schools to identify factors that may contribute to this disparity. Responses were received from 104 students at 36 allopathic medical schools. Most respondents identified as black (86.5%). One‐third of students (34.6%) noted that they were discouraged from pursuing otolaryngology due to lack of mentorship, and among these students, most noted that they lack mentors of the same race (75%). One‐fourth of respondents (25%) indicated that they lack a home otolaryngology program. The most common reasons for participants’ disinterest in otolaryngology included competitiveness, inadequate exposure, research, and the high board scores needed to match. This hypothesis‐generating, proof‐of‐concept study highlights potential barriers that may discourage underrepresented medical students from pursuing a career in otolaryngology.
Psychometric properties of a scale of attitudes toward musical genres linked to social groups in Peru
Authors: Pacheco Manuel , Espinosa Agustin , János Erika
Published: February 2022

The present research seeks to develop a scale that can measure attitudes toward different musical expressions representative of different social groups, such as the Andean and Afro-Peruvian groups. The participants were 312 individuals between 18 and 83 years of age ( M = 32.42, SD = 14.97), and the majority had no professional musical knowledge. First, Exploratory Factor Analysis was performed using the Unweighted Least Squares as the extraction method and using Oblimin rotation for the Andean and Afro-Peruvian musical genres. An identical factorial structure with two dimensions was found for both musical genres, obtaining optimal reliability according to Cronbach’s alpha coefficients. This similarity was verified by performing an invariance analysis, obtaining evidence that the proposed scale can be used regardless of the musical genre. Furthermore, correlation analyses were performed between the dimensions of the attitudes scale and variables such as stereotypes (toward the Andean and Afro-Peruvian social groups) and conservative ideology; the results provided evidence of discriminant validity. Finally, comparisons were made between musicians and non-musicians using the same dimensions of the attitude scale as evidence for criterion validity. The results are discussed based on scale’s optimal psychometric functioning, as well as its implications at the level of intergroup dynamics.
Police and Transgender and Gender Diverse People in the United States: A Brief Note on Interaction, Harassment, and Violence
Authors: Stenersen Madeline R. , Thomas Kathryn , McKee Sherry
Published: February 2022

Transgender and gender diverse (TGD) people in the United States continue to face dire rates of police violence and harassment. However, little research has examined this phenomenon using large-scale nationwide data. The current study utilized data from the United States Transgender Survey to examine the prevalence and correlates of police interaction, harassment, and violence among TGD people in the United States. Police harassment and violence types examined included reported incidences of (a) officers using the wrong pronouns, (b) officers asking about an individual’s transition, (c) verbal harassment, (d) physical attack, (e) forcing sex to avoid arrest, and (f) unwanted sexual contact from an officer. Results from a weighted sample of 22,456 TGD people revealed that 40.3% reported having interacted with the police in the past year. Among those who interacted with the police in the past year, 45.7% reported experiencing at least one incident of police verbal harassment and 6.1% reported at least one incidence of police physical/sexual violence in the past year. Engaging in sex work was one of the most consistent predictors of police interaction, harassment, and violence. Notably, sex workers were approximately 11 times more likely to report being forced to engage in sex with the police to avoid arrest when compared to non-sex workers. Overall, people of color also reported significantly higher rates of police harassment and violence compared to their White counterparts. Additional correlates included income, educational attainment, and participation in other illegal work. Taken together, the findings of the current study highlight the urgent need for additional examination, intervention, and advocacy to eliminate police harassment and violence against members of the TGD community in the United States.
Act East through India’s Northeast: Limits of Neoliberal Strategies towards Developing an Underdeveloped Region
Authors: Patgiri Rubul , Gogoi Dilip
Published: February 2022

One of the major objectives of the Look East, now rechristened as Act East Policy, of India is to develop the geographically and economically isolated region of Northeast India by economically integrating it with the neighbouring regions of South East Asia through neoliberal economic intervention. In view of this, the present article tries to analyse the rationale of such neoliberal-centric development model for the Northeast India as envisaged under the Look (Act) East Policy, existing gaps in the present policy framework and its impact. It argues that so far, such a strategy has brought very little dividend for the Northeast and may be at odds with some of the existing political, economic and social realities of the region. The article finally concludes by arguing that resources and interests of the region must be protected while trying to expose the region to global market economy for greater economic prosperity.
Secreted protein markers in oral squamous cell carcinoma (OSCC)
Authors: Mumtaz Madiha , Bijnsdorp Irene V. , Böttger Franziska , Piersma Sander R. , Pham Thang V. , Mumtaz Samiullah , Brakenhoff Ruud H. , Akhtar M. Waheed , Jimenez Connie R.
Published: February 2022

Background

Oral squamous cell carcinoma (OSCC) is a main cause of oral cancer mortality and morbidity in central south Asia. To improve the clinical outcome of OSCC patients, detection markers are needed, which are preferably non-invasive and thus independent of a tissue biopsy.

Methods

In the present study, we aimed to identify robust candidate protein biomarkers for non-invasive OSCC diagnosis. To this end, we measured the global protein profiles of OSCC tissue lysates to matched normal adjacent mucosa samples (n = 14) and the secretomes of nine HNSCC cell lines using LC–MS/MS-based proteomics.

Results

A total of 5123 tissue proteins were identified, of which 205 were robustly up- regulated (p-value < 0.01, fold change > + 2) in OSCC-tissues compared to normal adjacent tissues. The biological process “Secretion” was highly enriched in this set of proteins. Other upregulated biological pathways included “Unfolded Protein Response”, “Spliceosomal complex assembly”, “Protein localization to endosome” and “Interferon Gamma Response”. Transcription factor analysis implicated Creb3L1, ESRRA, YY, ELF2, STAT1 and XBP as potential regulators. Of the 205 upregulated tissue proteins, 132 were identified in the cancer cell line secretomes, underscoring their potential use as non-invasive biofluid markers. To further prioritize our candidate markers for non-invasive OSCC detection, we integrated our data with public biofluid datasets including OSCC saliva, yielding 25 candidate markers for further study.

Conclusions

We identified several key proteins and processes that are associated with OSCC tissues, underscoring the importance of altered secretion. Cancer-associated OSCC secretome proteins present in saliva have potential to be used as novel non-invasive biomarkers for the diagnosis of OSCC.

Graphical Abstract
Prediction of overall survival in patients with pancreatic ductal adenocarcinoma: histogram analysis of ADC value and correlation with pathological intratumoral necrosis
Authors: Noda Yoshifumi , Tomita Hiroyuki , Ishihara Takuma , Tsuboi Yoshiki , Kawai Nobuyuki , Kawaguchi Masaya , Kaga Tetsuro , Hyodo Fuminori , Hara Akira , Kambadakone Avinash R. , Matsuo Masayuki
Published: February 2022

Background

To evaluate the utility of histogram analysis (HA) of apparent diffusion coefficient (ADC) values to predict the overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC) and to correlate with pathologically evaluated massive intratumoral necrosis (MITN).

Materials and methods

Thirty-nine patients were included in this retrospective study with surgically resected PDAC who underwent preoperative magnetic resonance imaging. Twelve patients received neoadjuvant chemotherapy. HA on the ADC maps were performed to obtain the tumor HA parameters. Using Cox proportional regression analysis adjusted for age, time-dependent receiver-operating-characteristic (ROC) curve analysis, and Kaplan–Meier estimation, we evaluated the association between HA parameters and OS. The association between prognostic factors and pathologically confirmed MITN was assessed by logistic regression analysis.

Results

The median OS was 19.9 months. The kurtosis (P < 0.001), entropy (P = 0.013), and energy (P = 0.04) were significantly associated with OS. The kurtosis had the highest area under the ROC curve (AUC) for predicting 3-year survival (AUC 0.824) among these three parameters. Between the kurtosis and MITN, the logistic regression model revealed a positive correlation (P = 0.045). Lower survival rates occurred in patients with high kurtosis (cutoff value > 2.45) than those with low kurtosis (≤ 2.45) (P < 0.001: 1-year survival rate, 75.2% versus 100%: 3-year survival rate, 14.7% versus 100%).

Conclusions

HA derived kurtosis obtained from tumor ADC maps might be a potential imaging biomarker for predicting the presence of MITN and OS in patients with PDAC.
Erythropoietin and iron for anemia in HIV-infected patients undergoing maintenance hemodialysis in China: a cross-sectional study
Authors: Peng Lei , He Yanan , Zhang Jiong , Hong Daqing , Li Guisen
Published: February 2022

Background

Anemia is a common complication of chronic kidney disease (CKD) and HIV infection. The number of people living with HIV on hemodialysis (HD) is increasing. However, there is no data about anemia and related therapies in this kind of patients in China. We aim to assess the difference in hemoglobin (Hgb) and treatments like erythropoietin and iron between HIV-HD patients and HD patients in Chengdu, China.

Methods

This cross-sectional study was conducted with data collection from January 2020 to June 2020. Thirty-four HIV-infected HD patients and thirty-five non-HIV-infected HD patients were included. Age, gender, dialysis vintage, single-pool (sp) Kt/V, Hgb, the dose of erythropoietin, ferritin, use of iron preparations, and serum albumin were collected in all patients. Time since HIV diagnosis, counts of CD4 + T cells, HIV RNA, and antiretroviral therapy for HIV infection were collected in HIV-infected patients. T-test, Mann–Whitney U test, and chi-square statistics were applied in SPSS.

Results

The Hgb of HIV-HD and HD groups were 105.70 (95.93–112.08) g/L and 112.00 (93.00–126.00) g/L respectively (P = 0.064). There was a statistically significant higher erythropoietin dosage used in the HIV-HD population (222.55 ± 115.47 U/kg/week) compared to the HIV-negative HD group (161.86 ± 110.31 U/kg/week) (P = 0.029). 16/34 (47.06%) HIV-HD patients and 5/35 (14.29%) HD patients were treated with iron preparations (P = 0.003). The ferritin levels were 316.50 (117.38–589.75) ng/ml and 272.70 (205.00–434.00) ng/ml in HIV-HD and HD groups respectively.

Conclusions

A higher erythropoietin dosage and a higher probability of iron preparations may be required to maintain Hgb in HIV-HD patients compared with HD patients.
The short-term and oncologic outcomes of younger VS older colorectal cancer patients undergoing primary surgery: a propensity score matching analysis
Authors: Liu Xiao-Yu , Kang Bing , Cheng Yu-Xi , Yuan Chao , Tao Wei , Zhang Bin , Wei Zheng-Qiang , Peng Dong
Published: February 2022

Purpose

The purpose of the current study is to analyze the difference of short-term and oncologic outcomes between younger and older colorectal cancer (CRC) patients who underwent primary CRC surgery using a propensity score matching (PSM) analysis.

Methods

We retrospectively collected CRC patients who underwent primary surgery in a single clinical database from Jan 2011 to Jan 2020. The short-term and oncologic outcomes were compared between younger aged group and older aged group.

Results

A total of 4599 patients were included in this study, and there were 4196 patients in older aged group and 403 patients in younger aged group. After 1:1 ratio PSM, there were 401 patients in each group. No significant difference was found in terms of baseline information after PSM (p>0.05). Younger aged group had larger retrieved lymph nodes before (p<0.001) and after PSM (p=0.001) than older aged group. In multivariate analysis, younger age was an independent predictor of better overall survival (OS) (p<0.001, HR=2.303, 95% CI=1.658-3.199) and disease-free survival (DFS) (p=0.008, HR=1.425, 95% CI=1.098-1.850). In terms of different tumor stage after PSM, younger aged group had better OS than older group in stage II (p<0.001) and stage IV (p=0.028) CRC, and younger aged group had better DFS than older group in stage II (p=0.016) CRC.

Conclusion

Younger CRC patients had larger retrieved lymph nodes and better prognosis than older CRC patients after primary CRC surgery.
Lipid-lowering drug adherence and combination therapy effects on gastrointestinal cancer in patients with dyslipidemia without diabetes: a retrospective cohort study in South Korea
Authors: Han Kyu-Tae , Kim Seungju
Published: February 2022

Background

In aging populations, the number of people with high cholesterol levels is increasing. Appropriate management of high cholesterol levels with drugs such as statins may prevent secondary diseases. Despite many studies on the effects of statins on various types of cancer, the effectiveness of lipid-lowering therapy in preventing cancer remains controversial. This study aimed to evaluate its long-term effect on developing gastrointestinal (GI) cancer in patients with dyslipidemia.

Methods

This study used the National Health Insurance Sampling (NHIS) cohort data (2002–2015), which included patients with dyslipidemia without diabetes, and measured patients’ adherence to lipid-lowering therapy using the medication possession ratio. We used the Cox proportional hazard ratio (HR) to identify the association between the continuity of lipid-lowering therapy and the risk of GI cancer. We also evaluated the association between a combination of lipid-lowering drugs and a reduced risk of GI cancer.

Results

A total of 49,351 patients were diagnosed with dyslipidemia, of which 579 were diagnosed with GI cancer. Patients with higher adherence to lipid-lowering therapy had a significantly reduced risk of GI cancer compared to patients without drugs, and high adherence was associated with a reduced incidence of all types of GI cancer. Specifically, the combination of statins and ezetimibe or fibrates appears to reduce GI cancer risk effectively. Overall, the continuity of lipid-lowering therapy had a protective effect on GI cancer in middle-aged and elderly patients with dyslipidemia compared to non-users.

Conclusions

Our findings suggest that the continuity of lipid-lowering therapy is vital in patients with dyslipidemia. In addition, for individuals vulnerable to GI cancer, combination therapy may be associated with more effective protection against GI cancer. Healthcare providers need patient education and monitoring to improve drug adherence in patients with dyslipidemia.
Traumatic aniridia with extensive episcleral pigmentation: a case report
Authors: Yang Hsin-Yu , Liu Catherine Jui-Ling
Published: February 2022

Background

Traumatic aniridia has been documented in eyes with a history of cataract extraction through a clear corneal wound. The proposed hypothesis is that the iris tissue was squeezed out from the corneal wound as it is a relative weak point. However, traumatic aniridia with extensive pigmentation of the episclera has never been reported.

Case presentation

A patient, who has surgical histories of trabeculectomy and cataract surgery many years ago, presented with refractory high intraocular pressure (IOP), almost complete loss of the iris, and diffuse pigmentation of the episclera after he had suffered from a contusion injury. In addition to numerous pigment particles and cells in the anterior chamber and a well-centered intraocular lens, protruding uvea tissue with overlying conjunctiva adjacent to the site of trabeculectomy was noted. Gonioscopy showed absence of the iris with clear view of the ciliary body.

Conclusions

The distinct presentation of this case indicates that the torn iris was displaced to the trapdoor instead of the clear cornea incision and was confined to the subconjunctival space. The scleral fistula serves as a less resistant point for releasing pressure compared to a healed corneal wound when the eye encounters a contusion injury. Further treatment options to lower IOP include repeated trabeculectomy, implantation of glaucoma drainage device, and endoscopic cyclophotocoagulation. Transscleral cyclophotocoagulation may be considered only after episcleral pigmentation has become less so as to avoid the risk of surface burn.
Factors associated with faster axial elongation after orthokeratology treatment
Authors: Qi Ya , Liu Lizhou , Li Yu , Zhang Fengju
Published: February 2022

Background

To study the baseline factors that related to faster axial elongation after orthokeratology (OK) treatment and the characteristics of cases with axial length decrease in a group of myopia children.

Methods

This is a retrospective study. The records of 73 children who had wear OK lens for at least one year were reviewed. Only the data of right eyes were included. Baseline data included: age, gender, parental myopia, refractive error, corneal power, central corneal thickness, axial length and anterior chamber depth. Corneal power, central corneal thickness, anterior chamber depth and axial length after one-year of OK lens wear were also collected. The related factors affecting axial length change were analyzed. A comparison was made on the cases of axial length increase and axial length decrease.

Results

Of the 73 eyes, axial length increased by 0.18 ± 0.17 mm (P < 0.001) after one year of OK lens wear. Correlation analysis showed that one-year axial length change was negatively correlated with age and positively correlated with the parental myopia and baseline myopia. Stepwise multiple linear regression analysis showed that the factors associated with faster axial elongation were lower baseline myopic spherical equivalent (P = 0.018), higher parental myopia degree (P = 0.026), and younger age at the onset of lens wear. (P = 0.039). Nine eyes showed negative axial growth (−0.06 ± 0.04 mm), and had older initial age of lens wear, higher baseline myopic spherical equivalent, and lager baseline corneal power, when compared with cases of axial length increase.

Conclusions

Myopia children with lower baseline myopic spherical equivalent, younger initial age and higher parental myopia had faster axial elongation after orthokeratology treatment. More aggressive treatment should be considered. In children with slow axial elongation, OK lens wear may lead to negative axial growth. Whether there are reasons other than central corneal thinning and choroidal thickening needs further study.
Residents and staff perceptions of a pediatric clinical teaching unit in a large tertiary care center in Saudi Arabia
Authors: Hameed Tahir Kamal , Jamil Syed Furrukh , Alkhalaf Hamad Abdullah
Published: February 2022

Background

The clinical teaching unit (CTU) is a commonly used model of patient care and teaching. Despite being a common model of care, very few studies have looked at its impact on the education of trainees. In addition, it is a relatively new structure for pediatric inpatient care in Saudi Arabia. The purpose of this study was to compare postgraduate trainees (residents) and staff perceptions of the old and the new (the CTU) inpatient team structures, and to evaluate the impact of the CTU on residents’ education.

Methods

An online survey was sent to nurses, pediatric residents, and attending physicians who worked under both structures. Questions for residents were adopted from the National training survey of the General Medical Council, United Kingdom.

Results

A total of 147 pediatric healthcare workers completed the survey (97 nurses, 39 residents, and 11 attending physicians), most of whom worked in both the old and new inpatient team structures. More than 97% of residents reported being supervised by their attending on a daily basis in the CTU structure as compared with 15% in the old structure. A higher proportion of residents favored the old structure in terms of the opportunity it provided to develop their leadership skills. Eighty-seven percent of nurses believed the CTU had improved patient safety of pediatric inpatients. Overall, 82% of residents, 91% of nurses, and 100% of attending physicians favoured the CTU structure over the old inpatient model.

Conclusions

Our study shows that pediatric residents and staff perceived the CTU structure as superior to the old inpatient team structure, especially in terms of patient safety. Although the CTU seemed to have a positive impact on residents’ education, this must be further examined especially with respect to its impact on residents’ leadership skills.
A qualitative study of an undergraduate online emergency medicine education program at a teaching Hospital in Kampala, Uganda
Authors: Ayoola Adeoluwa S. , Acker Peter C. , Kalanzi Joseph , Strehlow Matthew C. , Becker Joseph U. , Newberry Jennifer A.
Published: February 2022

Background

Globally, half of all years of life lost is due to emergency medical conditions, with low- and middle-income countries (LMICs) facing a disproportionate burden of these conditions. There is an urgent need to train the future physicians in LMICs in the identification and stabilization of patients with emergency medical conditions. Little research focuses on the development of effective emergency medicine (EM) medical education resources in LMICs and the perspectives of the students themselves. One emerging tool is the use of electronic learning (e-learning) and blended learning courses. We aimed to understand Uganda medical trainees’ use of learning materials, perception of current e-learning resources, and perceived needs regarding EM skills acquisition during participation in an app-based EM course.

Methods

We conducted semi-structured interviews and focus groups of medical students and EM residents. Participants were recruited using convenience sampling. All sessions were audio recorded and transcribed verbatim. The final codebook was approved by three separate investigators, transcripts were coded after reaching consensus by all members of the coding team, and coded data were thematically analyzed.

Results

Twenty-six medical trainees were included in the study. Analysis of the transcripts revealed three major themes: [1] medical trainees want education in EM and actively seek EM training opportunities; [2] although the e-learning course supplements knowledge acquisition, medical students are most interested in hands-on EM-related training experiences; and [3] medical students want increased time with local physician educators that blended courses provide.

Conclusions

Our findings show that while students lack access to structured EM education, they actively seek EM knowledge and practice experiences through self-identified, unstructured learning opportunities. Students value high quality, easily accessible EM education resources and employ e-learning resources to bridge gaps in their learning opportunities. However, students desire that these resources be complemented by in-person educational sessions and executed in collaboration with local EM experts who are able to contextualize materials, offer mentorship, and help students develop their interest in EM to continue the growth of the EM specialty.
Hospital factor and prognosis of COVID-19 in New York City, the United States of America: insights from a retrospective cohort study
Authors: Takahashi Mai , Egorova Natalia N. , Iwagami Masao , Kuno Toshiki
Published: February 2022

Background

April 22nd, 2020, New York City (NYC) was the epicenter of the pandemic of Coronavirus disease 2019 (COVID-19) in the US with differences of death rates among its 5 boroughs. We aimed to investigate the difference in mortality associated with hospital factors (teaching versus community hospital) in NYC.

Design

Retrospective cohort study.

Methods

We obtained medical records of 6509 hospitalized patients with laboratory confirmed COVID-19 from the Mount Sinai Health System including 4 teaching hospitals in Manhattan and 2 community hospitals located outside of Manhattan (Queens and Brooklyn) retrospectively. Propensity score analysis using inverse probability of treatment weighting (IPTW) with stabilized weights was performed to adjust for differences in the baseline characteristics of patients initially presenting to teaching or community hospitals, and those who were transferred from community hospitals to teaching hospitals.

Results

Among 6509 patients, 4653 (72.6%) were admitted in teaching hospitals, 1462 (22.8%) were admitted in community hospitals, and 293 (4.6%) were originally admitted in community and then transferred into teaching hospitals. Patients in community hospitals had higher mortality (42.5%) than those in teaching hospitals (17.6%) or those transferred from community to teaching hospitals (23.5%, P < 0.001). After IPTW-adjustment, when compared to patients cared for at teaching hospitals, the hazard ratio (HR) and 95% confidence interval (CI) of mortality were as follows: community hospitals 2.47 (2.03-2.99); transfers 0.80 (0.58-1.09)).

Conclusions

Patients admitted to community hospitals had higher mortality than those admitted to teaching hospitals.
Screens in fly and beetle reveal vastly divergent gene sets required for developmental processes
Authors: Hakeemi Muhammad Salim , Ansari Salim , Teuscher Matthias , Weißkopf Matthias , Großmann Daniela , Kessel Tobias , Dönitz Jürgen , Siemanowski Janna , Wan Xuebin , Schultheis Dorothea , Frasch Manfred , Roth Siegfried , Schoppmeier Michael , Klingler Martin , Bucher Gregor
Published: February 2022

Background

Most of the known genes required for developmental processes have been identified by genetic screens in a few well-studied model organisms, which have been considered representative of related species, and informative—to some degree—for human biology. The fruit fly Drosophila melanogaster is a prime model for insect genetics, and while conservation of many gene functions has been observed among bilaterian animals, a plethora of data show evolutionary divergence of gene function among more closely-related groups, such as within the insects. A quantification of conservation versus divergence of gene functions has been missing, without which it is unclear how representative data from model systems actually are.

Results

Here, we systematically compare the gene sets required for a number of homologous but divergent developmental processes between fly and beetle in order to quantify the difference of the gene sets. To that end, we expanded our RNAi screen in the red flour beetle Tribolium castaneum to cover more than half of the protein-coding genes. Then we compared the gene sets required for four different developmental processes between beetle and fly. We found that around 50% of the gene functions were identified in the screens of both species while for the rest, phenotypes were revealed only in fly (~ 10%) or beetle (~ 40%) reflecting both technical and biological differences. Accordingly, we were able to annotate novel developmental GO terms for 96 genes studied in this work. With this work, we publish the final dataset for the pupal injection screen of the iBeetle screen reaching a coverage of 87% (13,020 genes).

Conclusions

We conclude that the gene sets required for a homologous process diverge more than widely believed. Hence, the insights gained in flies may be less representative for insects or protostomes than previously thought, and work in complementary model systems is required to gain a comprehensive picture. The RNAi screening resources developed in this project, the expanding transgenic toolkit, and our large-scale functional data make T. castaneum an excellent model system in that endeavor.
Capillary microscopy is a potential screening method for connective tissue disease in children with Raynaud’s phenomenon
Authors: Farenhorst Claudette A. , Roon Anniek M. , Gessel Anne I. , Stel Alja J. , Bootsma Hendrika , Armbrust Wineke , Mulder Douwe J.
Published: February 2022

Background

Nailfold capillary microscopy (NCM) is a cornerstone in the diagnosis of Systemic Sclerosis (SSc) in adulthood. Although Raynaud’s phenomenon (RP) is very common in childhood, studies on diagnostic methods to differentiate between primary RP (PRP) and secondary RP (SRP) at a young age are scarce. The aim of this study was to determine the value of NCM in differentiating between PRP and SRP in children and adolescents with RP.

Methods

In this nested case–control study, 83 patients diagnosed with RP and having underwent NCM in childhood were retrospectively included. Based on whether they were diagnosed with a connective tissue disease (CTD) during follow-up, patients were classified as PRP or SRP. NCM was performed by a vascular technician. PRP and SRP patients were compared on demographics, NCM and serology. Variables associated with SRP were included in a multivariate logistic regression model. Predictive values were calculated for NCM, ANA positivity and the combination of NCM and ANA positivity.

Results

At the time of the NCM, the mean age of the RP patients was 15.4 ± 2.3 years. Of these patients, 78.3% were classified as PRP and 21.7% as SRP at mean follow-up of 6.4 ± 3.20 years. CTDs were miscellaneous, with only one patient having developed SSc. Of the NCM parameters, only capillary loss was associated with SRP (p = 0.01). In a multivariate logistic regression model including ANA, capillary loss was not a predictor of SRP. In a model without ANAs, capillary loss was an independent predictor (OR = 3.98, CI 95% 1.22–12.99). Capillary loss had a sensitivity of 44.4% and a specificity of 84.4% for SRP. ANA combined with capillary loss had a sensitivity of 66.7% and a specificity of 85.7%.

Conclusion

Whereas RP in adulthood is most strongly associated with SSc, children with RP seem to be at risk for developing other CTDs with less apparent NCM abnormalities. Of all NCM findings, only capillary loss was predictive for SRP. NCM did not add to the predictive value of ANA screening. However, with a specificity of 84.4% and being non-invasive, NCM shows potential as a screening method for SRP. More research with a larger study population is required before drawing conclusions.
PD-L1 signaling in reactive astrocytes counteracts neuroinflammation and ameliorates neuronal damage after traumatic brain injury
Authors: Gao Xiang , Li Wei , Syed Fahim , Yuan Fang , Li Ping , Yu Qigui
Published: February 2022

Background

Tissue damage and cellular destruction are the major events in traumatic brain injury (TBI), which trigger sterile neuroimmune and neuroinflammatory responses in the brain. While appropriate acute and transient neuroimmune and neuroinflammatory responses facilitate the repair and adaptation of injured brain tissues, prolonged and excessive neuroimmune and neuroinflammatory responses exacerbate brain damage. The mechanisms that control the intensity and duration of neuroimmune and neuroinflammatory responses in TBI largely remain elusive.

Methods

We used the controlled cortical impact (CCI) model of TBI to study the role of immune checkpoints (ICPs), key regulators of immune homeostasis, in the regulation of neuroimmune and neuroinflammatory responses in the brain in vivo.

Results

We found that de novo expression of PD-L1, a potent inhibitory ICP, was robustly and transiently induced in reactive astrocytes, but not in microglia, neurons, or oligodendrocyte progenitor cells (OPCs). These PD-L1+reactive astrocytes were highly enriched to form a dense zone around the TBI lesion. Blockade of PD-L1 signaling enlarged brain tissue cavity size, increased infiltration of inflammatory Ly-6CHighmonocytes/macrophages (M/Mɸ) but not tissue-repairing Ly-6CLowF4/80+M/Mɸ, and worsened TBI outcomes in mice. PD-L1 gene knockout enhanced production of CCL2 that is best known for its ability to interact with its cognate receptor CCR2 on Ly-6CHighM/Mϕto chemotactically recruit these cells into inflammatory sites. Mechanically, PD-L1 signaling in astrocytes likely exhibits dual inhibitory activities for the prevention of excessive neuroimmune and neuroinflammatory responses to TBI through (1) the PD-1/PD-L1 axis to suppress the activity of brain-infiltrating PD-1+immune cells, such as PD-1+T cells, and (2) PD-L1 intrinsic signaling to regulate the timing and intensity of astrocyte reactions to TBI.

Conclusions

PD-L1+astrocytes act as a gatekeeper to the brain to control TBI-related neuroimmune and neuroinflammatory responses, thereby opening a novel avenue to study the role of ICP–neuroimmune axes in the pathophysiology of TBI and other neurological disorders.
Prenatal inflammation causes obesity and abnormal lipid metabolism via impaired energy expenditure in male offspring
Authors: Ni Meng , Zhang Qianqian , Zhao Jiuru , Yao Dongting , Wang Tao , Shen Qianwen , Li Wei , Li Baihe , Ding Xiya , Liu Zhiwei
Published: February 2022

Introduction

Obesity has becoming a global health issue. Fetus exposed to adversity in the uterine are susceptible to unhealth stimulus in adulthood. Prenatal inflammation is related to poor neonatal outcomes like neurodevelopmental impairments and respiratory complications. Recent studies suggested prenatal lipopolysaccharide (LPS) exposure could result in metabolic disorders. Thus, we hypothesized that offspring exposed to prenatal inflammation could develop into metabolic disorder.

Methods

The pregnant C57BL/6J mice were intraperitoneally injected with 50 μg/kg LPS or saline only once at GD15. The male offspring were weighted weekly until sacrificed. Indirect calorimetry and body composition were both performed at 9 and 18 weeks old. At 20 weeks old, mice were fasted overnight before collecting blood samples and liver for metabolomics analysis and RNA sequencing, respectively. Differentially expressed genes were further verified by RT-qPCR and western blotting.

Results

Prenatal inflammation resulted in obesity with increased fat percentage and decreased energy expenditure in middle-age male offspring. Abnormal lipid accumulation, changes of gene expression profile and upregulation of multi-component mechanistic target of rapamycin complex 1 (mTOR)/Peroxisome proliferator-activated receptor-γ pathway was observed in liver, accompanied with decreased bile acids level, unsaturated fatty acids androgens and prostaglandins in serum. Indirect calorimetry showed increased respiratory exchange rate and deceased spontaneous activity at 9 weeks in LPS group. Impaired energy expenditure was also observed at 18 weeks in LPS group.

Conclusion

Prenatal LPS exposure led to obesity and abnormal lipid metabolism through impaired energy expenditure.
CNS endothelial derived extracellular vesicles are biomarkers of active disease in multiple sclerosis
Authors: Mazzucco Michael , Mannheim William , Shetty Samantha V. , Linden Jennifer R.
Published: February 2022

Background

Multiple sclerosis (MS) is a complex, heterogenous disease characterized by inflammation, demyelination, and blood–brain barrier (BBB) permeability. Currently, active disease is determined by physician confirmed relapse or detection of contrast enhancing lesions via MRI indicative of BBB permeability. However, clinical confirmation of active disease can be cumbersome. As such, disease monitoring in MS could benefit from identification of an easily accessible biomarker of active disease. We believe extracellular vesicles (EV) isolated from plasma are excellent candidates to fulfill this need. Because of the critical role BBB permeability plays in MS pathogenesis and identification of active disease, we sought to identify EV originating from central nervous system (CNS) endothelial as biomarkers of active MS. Because endothelial cells secrete more EV when stimulated or injured, we hypothesized that circulating concentrations of CNS endothelial derived EV will be increased in MS patients with active disease.

Methods

To test this, we developed a novel method to identify EV originating from CNS endothelial cells isolated from patient plasma using flow cytometry. Endothelial derived EV were identified by the absence of lymphocyte or platelet markers CD3 and CD41, respectively, and positive expression of pan-endothelial markers CD31, CD105, or CD144. To determine if endothelial derived EV originated from CNS endothelial cells, EV expressing CD31, CD105, or CD144 were evaluated for expression of the myelin and lymphocyte protein MAL, a protein specifically expressed by CNS endothelial cells compared to endothelial cells of peripheral organs.

Results

Quality control experiments indicate that EV detected using our flow cytometry method are 0.2 to 1 micron in size. Flow cytometry analysis of EV isolated from 20 healthy controls, 16 relapsing–remitting MS (RRMS) patients with active disease not receiving disease modifying therapy, 14 RRMS patients with stable disease not receiving disease modifying therapy, 17 relapsing-RRMS patients with stable disease receiving natalizumab, and 14 RRMS patients with stable disease receiving ocrelizumab revealed a significant increase in the plasma concentration of CNS endothelial derived EV in patients with active disease compared to all other groups (p = 0.001). Conclusions: For the first time, we have identified a method to identify CNS endothelial derived EV in circulation from human blood samples. Results from our pilot study indicate that increased levels of CNS endothelial derived EV may be a biomarker of BBB permeability and active disease in MS.
Development of a split fluorescent protein-based RNA live-cell imaging system to visualize mRNA distribution in plants
Authors: Huang Nien-Chen , Luo Kai-Ren , Yu Tien-Shin
Published: February 2022

Background

RNA live-cell imaging systems have been used to visualize subcellular mRNA distribution in living cells. The RNA-binding protein (RBP)-based RNA imaging system exploits specific RBP and the corresponding RNA recognition sequences to indirectly label mRNAs. Co-expression of fluorescent protein-fused RBP and target mRNA conjugated with corresponding RNA recognition sequences allows for visualizing mRNAs by confocal microscopy. To minimize the background fluorescence in the cytosol, the nuclear localization sequence has been used to sequester the RBP not bound to mRNA in the nucleus. However, strong fluorescence in the nucleus may limit the visualization of nucleus-localized RNA and sometimes may interfere in detecting fluorescence signals in the cytosol, especially in cells with low signal-to-noise ratio.

Results

We eliminated the background fluorescence in the nucleus by using the split fluorescent protein-based approach. We fused two different RBPs with the N- or C-terminus of split fluorescent proteins (FPs). Co-expression of RBPs with the target mRNA conjugated with the corresponding RNA recognition sequences can bring split FPs together to reconstitute functional FPs for visualizing target mRNAs. We optimized the system with minimal background fluorescence and used the imaging system to visualize mRNAs in living plant cells.

Conclusions

We established a background-free RNA live-cell imaging system that provides a platform to visualize subcellular mRNA distribution in living plant cells.
Do clinical guidelines facilitate or impede drivers of treatment in Fabry disease?
Authors: Hughes Derralynn A. , Aguiar Patrício , Lidove Olivier , Nicholls Kathleen , Nowak Albina , Thomas Mark , Torra Roser , Vujkovac Bojan , West Michael L. , Feriozzi Sandro
Published: February 2022

Background

Variable disease progression confounds accurate prognosis in Fabry disease. Evidence supports the long-term benefit of early intervention with disease-specific therapy, but current guidelines recommend treatment initiation based on signs that may present too late to avoid irreversible organ damage. Findings from the ‘PRoposing Early Disease Indicators for Clinical Tracking in Fabry Disease’ (PREDICT-FD) initiative included expert consensus on 27 early indicators of disease progression in Fabry disease and on drivers of and barriers to treatment initiation in Fabry disease. Here, we compared the PREDICT-FD indicators with guidance from the European Fabry Working Group and various national guidelines to identify differences in signs supporting treatment initiation and how guidelines themselves might affect initiation. Finally, anonymized patient histories were reviewed by PREDICT-FD experts to determine whether PREDICT-FD indicators supported earlier treatment than existing guidance.

Results

Current guidelines generally aligned with PREDICT-FD on indicators of renal involvement, but most lacked specificity regarding cardiac indicators. The prognostic significance of neurological indicators such as white matter lesions (excluded by PREDICT-FD) was questioned in some guidelines and excluded from most. Some PREDICT-FD patient-reported signs (e.g., febrile crises) did not feature elsewhere. Key drivers of treatment initiation in PREDICT-FD were: (A) male sex, young age, and clinical findings (e.g., severe pain, organ involvement), (B) improving clinical outcomes and preventing disease progression, and (C) a family history of Fabry disease (especially if outcomes were severe). All guidelines aligned with (A) and several advocated therapy for asymptomatic male patients. There was scant evidence of (B) in current guidance: for example, no countries mandated ancillary symptomatic therapy, and no guidance advocated familial screening with (C) when diagnosis was confirmed. Barriers were misdiagnosis and a lack of biomarkers to inform timing of treatment. Review of patient histories generally found equal or greater support for treatment initiation with PREDICT-FD indicators than with other guidelines and revealed that the same case and guideline criteria often yielded different treatment recommendations.

Conclusions

Wider adoption of PREDICT-FD indicators at a national level could promote earlier treatment in Fabry disease. Clearer, more concise guidance is needed to harmonize treatment initiation in Fabry disease internationally.