bluuebunny/crossref_metadata_2025 huggingface dataset:
God’s Promise to Hagar in Genesis 16: Rethinking a Problematic Text
Authors: Krayer Patrick
Published: June 2022

God made an incredible promise to Hagar in Gen 16.12; however, the beauty of the promise gets lost in translation. Our English Bibles typically render this promise in a pejorative manner, which has led to centuries of stigmatizing Arabs, primarily Muslim Arabs. The polyvalence of the Hebrew in the verse opens the door for significantly different renderings of God’s promise. Thus, the assumptions translators bring to the text can easily shape their understandings. This paper works through the Hebrew and proposes a suitable alternative to traditional renderings, one that is sensitive to the immediate narrative context and to the broader biblical record. Fresh reflection on this verse can lead to corrected translations and the intentional elimination of any sacred justification for this stigmatization.
Appropriateness versus Naturalness in the Jamaican Creole Bible Translation Project
Authors: Jones Byron M.
Published: June 2022

In May 2007, the Bible Society of the West Indies (BSWI) announced its translation of the New Testament into Jamaican Creole. This paper examines the perceived weak point of the project, the issue of the “crudity” or “vulgarity” of the Jamaican language in the area of sexuality, which renders it unsuitable for the holy Scriptures. The project designed a set of focus-group instruments to test acceptability in the area of sexual terminology. Findings indicated that focus-group participants generally preferred the uses of English-like forms rather than the more natural Jamaican Creole ones when dealing with sexual concepts. They preferred prignant over briid or get beli, and vorjin over uman we neva tek man yet, and so on. The challenge to the project was how to manage the association of Jamaican sexual terms with vulgarity while remaining faithful to the language. The paper concludes with an account of how this was managed.
Taking the Potholes out of the Road: Prepublication Recording as a Means of Editing in Oral Preference Cultures
Authors: Wade Martha L.
Published: June 2022

Many translation projects begin typesetting almost immediately after a “final read through” which may come six months to a year after the final book is checked by a consultant. For some groups, however, following this standard methodology leaves them with an uneven translation that has been produced over several decades and checked by a variety of consultants. In one group, the translation was described as being like a road with potholes. In this paper, the methodology and results of using prepublication recording in two languages of Papua New Guinea will be examined and the impact of distributing prepublication recordings will be described. There is no doubt that prepublication recording is not an “efficient” process. It is expensive and time-consuming, but the resulting improvement in the translation makes it worth the effort.
Exploring Factors Associated With Family Caregivers’ Preparedness to Care for an Older Family Member Together With Home Care Nurses: An Analysis in a Swiss Urban Area
Authors: Ris Irène , Volken Thomas , Schnepp Wilfried , Mahrer-Imhof Romy
Published: June 2022

Introduction:

Home-dwelling older people with chronic diseases often need the support of informal and formal caregivers in order to continue living at home. Family members, however, need to be willing and prepared for caregiving together with home care nurses.

Objectives:

The purpose of this study was to explore factors associated with family caregivers’ preparedness to care for older home-dwelling adults who also receive home care nursing services.

Methods:

For this cross-sectional correlational study, a structured questionnaire was sent to family caregivers of adults aged 65 years or older receiving services from a community care agency. A total of 243 participants returned the questionnaire, of which 199 could be analyzed.

Results:

The stepwise backward regression model explained 29.1% of the variance of family caregivers’ preparedness. Mutuality was the most strongly associated factor with family caregivers’ preparedness whereas professional involvement of family caregiver in care process was important as well. Care intensity showed no significant impact.

Conclusion:

Nurses should support the whole family emotionally, and appreciate, admire, reinforce, and respect the caregivers’ situation. Home care nurses need to invest in helping families to find solutions, to strengthen their relationships between family members and the older person dwelling at home.
When Proficiency and Education Matter: The Mediating Role of English Proficiency and Moderating Effect of Parents’ Education in the SES–Academic Achievement Relationship During EMI
Authors: Muttaqin Syariful , Chuang Hsueh-Hua , Lin Ching-Hui , Cheng Ming-Min
Published: June 2022

This study investigated how socioeconomic status (SES) is associated with academic achievement and English proficiency in an English-medium instruction (EMI) program at a state university in Indonesia. It also examined the mediating effect of English proficiency and moderating effect of parents’ education on the relationship between SES and academic achievement. Data for 234 EMI students were obtained from the academic office of the university. Based on mediation analysis, SES significantly predicted students’ academic achievement and English proficiency. However, it stopped being a significant predictor when mediated through English proficiency. The moderation analysis shows that the degree of increase in EMI students’ grade point average was affected by the level of parents’ education when associated with family income. The article also presents the implications of the findings in enhancing university EMI programs and suggestions for future research.
Donor site morbidity in autologous bone grafting – A comparison between different techniques of anterior iliac crest bone harvesting: A prospective study
Authors: Tonk Gyneshwar , Yadav Pradeep KR , Agarwal Sumit , Jamoh Kalom
Published: June 2022

Background: The aim of this study is to compare morbidities at the donor site in autologous bone harvesting from an anterior iliac crest via the outer cortex, inner cortex and table splitting technique. Methods: The randomized, prospective and comparative study was conducted in 60 patients who were treated with bone grafting as a part of their treatment plan. Group A underwent the outer cortex technique (20 patients), Group B underwent the inner cortex technique (20 patients) and Group C underwent the table splitting technique (20 patients). The comparison of morbidities associated with various techniques of anterior iliac crest bone graft harvesting was done for a period of one year. Results: Most common morbidity observed was pain, measured by the visual analogue scale score (60/60, 100% of patients). The visual analogue scale score was significantly higher for the outer cortex group followed by the inner cortex group, and then the lowest score was for the table splitting group ( p < 0.05). Followed by numbness (40/60, 66%), least in the table splitting group and maximum in the outer cortex group ( p < 0.05). Next was abnormal gait, which was mostly seen in patients with the outer table method and least in the table split group ( p < 0.05). Other complications were infections (4), itching at the surgical site (3) and hematoma (1). There were no significant difference regarding scar satisfaction among comparison groups. Conclusion: we conclude that few differences do exist in harvest-site morbidities between different techniques used in our study. Overall, the most common morbidity observed were pain, numbness and abnormal gait. However, the table splitting group has the lowest morbidity, therefore bone harvesting by the table splitting appears to be a very good option.
Labor Immobility, Stability Discourse, and LGBQ Young Adults’ Career Plans in Japan
Authors: Ueno Koji
Published: June 2022

Recent US studies showed that many lesbian, gay, bisexual, and queer (LGBQ) young adults develop hopeful views about their occupational careers by emphasizing future workplaces’ friendly climates and denying their risk of experiencing discrimination. The results may partly reflect American labor market conditions and social discourses that endorse these views, and little is known about how LGBQ young adults may perceive their career chances and make plans in different labor market and discursive conditions. To extend the literature, the present study focuses on LGBQ young adults in Japan and contrast the results to those from a US study based on an equivalent design. Analysis of in-depth interviews highlighted Japanese LGBQ young adults’ anticipation of chilly industry climates. Further, they disengaged sexuality from their career plans by prioritizing career stability over industry climates and by deciding to hide their sexual identities from their future colleagues. They explained these decisions by addressing the importance of labor immobility and by drawing on a social discourse that linked career stability to a better life. Overall, the results underscored that the ways in which people respond to social marginalization greatly depend on what structural resources and constraints exist and what social discourses are present in the national context.
European Immigration and Patterns of Intra- and Interracial Mortality Inequality in the United States, 1900 to 1960
Authors: Bakhtiari Elyas
Published: June 2022

European immigrants to the United States in the early twentieth century occupied a “middle tier” in the ethnoracial hierarchy. The author uses mortality data disaggregated by nativity (1900–1960) and parental nativity (1900–1920) to examine intraracial and interracial mortality inequalities during this period. The findings suggest that variation within the white population mirrored the ethnoracial hierarchy: the U.S.-born white population with U.S.-born parents had the lowest rates of mortality from 1900 to 1920, and the foreign-born white population had higher rates than their U.S.-born counterparts. Given this heterogeneity, interracial inequality is higher when various U.S.-born white populations are the reference. Disaggregation also reveals divergent trends, such as the exceptionally high foreign-born mortality rates during the 1918 influenza pandemic. The findings suggest that analyses of mortality inequalities that rely on white population averages may understate intra- and interracial inequalities in relation to the ethnoracial hierarchy of the era.
The Dilemmas of Spatializing Social Issues
Authors: Calderón-Figueroa Fernando A. , Silver Daniel , Bidian Olimpia
Published: June 2022

Cities have established official neighborhood boundaries for targeted social policy in recent decades. The authors propose that a sociological conception of neighborhoods sensitizes us to the potential consequences of imposing categorical divisions onto a largely continuous urban space. The authors specify this idea in three steps. First, they argue that designations affect people’s behavior toward target neighborhoods. Second, the heterogeneity within official boundaries may lead to informational distortion; disadvantaged areas are denied benefits solely because of location. Third, designations may generate negative reputations for targeted areas or extend existing stigma to new areas. To examine these processes, the authors study Toronto’s Priority Area Program (2006–2013). Difference-in-difference models show significant negative effects of the designation on rent, home value, and building permits. The authors provide evidence of informational distortion through income distribution analysis. An analysis of policy documents, newspaper reports, and secondary literature illustrates the stigmatizing aspects that local community members and observers interpreted about the designation.
Psychological distance and fear of crime: Towards a new understanding of risk perception formation
Authors: Mellberg Jacques , Chataway Michael L , Ball Matthew J , Miles-Johnson Toby
Published: June 2022

The current study seeks to enhance the theoretical development of fear of crime by exploring the complex cognitive processes involved in risk perception formation. We apply Trope and Liberman’s construal level theory (CLT) of psychological distance to understand how and why these complex cognitive processes might shape an individual’s worry about crime. We pilot survey measures designed to capture perceptions of psychological distance and worry about crime using a convenience sample of N = 265 residents from Townsville, Queensland, Australia. Results of confirmatory factor analyses (CFA) reveal that these new measures have good scaling properties and that each dimension of psychological distance is empirically distinct. Multiple linear regression demonstrates that temporal, social and hypothetical psychological distance predicted worry at a statistically significant level, however, spatial distance was in the expected direction but was not statistically significant. These findings suggest that CLT is an appropriate lens to understand how individuals perceive their risk of criminal victimisation, but further research is needed to refine spatial distance survey measures. We recommend future research explores how psychological distance may interact with other well-known correlates of worry, such as age, gender and ethnicity.
Effect of chronic intermittent hypoxia-induced HIF-1α/ATAD2 expression on lung cancer stemness
Authors: Hao Shengyu , Li Fan , Jiang Pan , Gao Jian
Published: June 2022

Background

Obstructive sleep apnea is associated with increased lung cancer incidence and mortality. Cancer stem cells (CSCs) are characterized by their self-renewing ability, which contributes to metastasis, recurrence, and drug resistance. ATPase family AAA domain-containing protein 2 (ATAD2) induces malignancy in different types of tumors. However, a correlation between ATAD2 expression and CSCs in lung cancer has not yet been reported.

Methods

The relative messenger RNA (mRNA) levels of ATAD2, CD44, CD133, and hypoxia-inducible factor (HIF)-1α were determined using reverse-transcription quantitative polymerase chain reaction. ATAD2 protein levels were determined using Western blotting. Cell counting kit-8, 5-ethynyl-2′-deoxyuridine (EdU), and colony formation assays were performed to analyze the proliferation of lung cancer cells. Transwell migration and invasion assays were performed to evaluate cell migration and invasion, respectively. Tumor sphere formation analysis was used to determine tumor spheroid capacity. The link between ATAD2 and HIF-1α was verified using a dual-luciferase reporter assay. Immunofluorescence staining was performed to assess mitochondrial reactive oxygen species (mtROS) production. Flow cytometry analysis was conducted to determine the CD133 and CD44 positive cell ratio.

Results

We evaluated the relative expression of ATAD2 in four lung cancer cell lines (A549, SPC-A1, H460, and H1299 cells) and found increased mRNA and protein levels of ATAD2 in lung cancer samples. ATAD2 overexpression was a poor prognostic factor for lung cancer patients. Loss of ATAD2 reduced lung cancer cell viability and proliferation. Additionally, ATAD2 knockdown repressed lung cancer cell migration, invasion, stem-cell-like properties, and mtROS production. Chronic intermittent hypoxia (CIH)-induced HIF-1α expression significantly activated ATAD2 during lung cancer progression.

Conclusions

This study found that CIH induced HIF-1α expression, which acts as a transcriptional activator of ATAD2. The present study also suggests a novel mechanism by which the integrity of CIH-triggered HIF-1α/ATAD2 may determine lung cancer aggressiveness via the interplay of mtROS and stemness in lung cancer cells.
OptNCMiner: a deep learning approach for the discovery of natural compounds modulating disease-specific multi-targets
Authors: Shin Seo Hyun , Oh Seung Man , Yoon Park Jung Han , Lee Ki Won , Yang Hee
Published: June 2022

Background

Due to their diverse bioactivity, natural product (NP)s have been developed as commercial products in the pharmaceutical, food and cosmetic sectors as natural compound (NC)s and in the form of extracts. Following administration, NCs typically interact with multiple target proteins to elicit their effects. Various machine learning models have been developed to predict multi-target modulating NCs with desired physiological effects. However, due to deficiencies with existing chemical-protein interaction datasets, which are mostly single-labeled and limited, the existing models struggle to predict new chemical-protein interactions. New techniques are needed to overcome these limitations.

Results

We propose a novel NC discovery model called OptNCMiner that offers various advantages. The model is trained via end-to-end learning with a feature extraction step implemented, and it predicts multi-target modulating NCs through multi-label learning. In addition, it offers a few-shot learning approach to predict NC-protein interactions using a small training dataset. OptNCMiner achieved better prediction performance in terms of recall than conventional classification models. It was tested for the prediction of NC-protein interactions using small datasets and for a use case scenario to identify multi-target modulating NCs for type 2 diabetes mellitus complications.

Conclusions

OptNCMiner identifies NCs that modulate multiple target proteins, which facilitates the discovery and the understanding of biological activity of novel NCs with desirable health benefits.
QuickPed: an online tool for drawing pedigrees and analysing relatedness
Authors: Vigeland Magnus D.
Published: June 2022

Background

The ubiquity of pedigrees in many scientific areas calls for versatile and user-friendly software. Previously published online pedigree tools have limited support for complex pedigrees and do not provide analysis of relatedness between pedigree members.

Results

We introduce QuickPed, a web application for interactive pedigree creation and analysis. It supports complex inbreeding and comes with a rich built-in library of common and interesting pedigrees. The program calculates all standard coefficients of relatedness, including inbreeding, kinship and identity coefficients, and offers specialised plots for visualising relatedness. It also implements a novel algorithm for describing pairwise relationships in words.

Conclusion

QuickPed is a user-friendly pedigree tool aimed at researchers, case workers and teachers. It contains a number of features not found in other similar tools, and represents a significant addition to the body of pedigree software by making advanced relatedness analyses available for non-bioinformaticians.
Comprehensive evaluation of the effects of long-term cryopreservation on peripheral blood mononuclear cells using flow cytometry
Authors: Li Bo , Yang Chunmei , Jia Gui , Liu Yansheng , Wang Na , Yang Fangfang , Su Rui , Shang Yulong , Han Ying
Published: June 2022

Human peripheral blood mononuclear cells (PBMCs) originate from hematopoietic stem cells in the bone marrow, which mainly includes lymphocytes (T cells, B cells, and natural killer cells) and monocytes. Cryopreserved PBMCs providing biobank resources are crucial for clinical application or scientific research. Here, we used flow cytometry to explore the influence of long-term cryopreservation on the quality of PBMCs with the aim of providing important evidence for the effective utilization of biobank resources. The PBMCs were isolated from the peripheral blood, which was collected from volunteers in the hospital. After long-term cryopreservation in liquid nitrogen, we analyzed the changes in cell numbers, viability, and multiple subtypes of PBMCs and studied the apoptosis, proliferation, activation, function, and status of T cells in comparison with freshly isolated PBMCs by flow cytometry, and then further tracked the effects of long-term cryopreservation on the same sample. Although the different cell types in the PBMCs dynamically changed compared with those in the freshly isolated samples, PBMC recovery and viability remained stable after long-term cryopreservation, and the number of most innate immune cells (e.g., monocytes and B cells) was significantly reduced compared to that of the freshly isolated PBMCs or long-term cryopreserved PBMCs; more importantly, the proportion of T cell subtypes, apoptosis, proliferation, and functional T cells, except for Tregs, were not affected by long-term cryopreservation. However, the proportions of activated T, naïve T, central memory T, effector T, and effector memory T cells dynamically changed after long-term cryopreservation. This article provides important evidence for the effective utilization of biobank resources. Long-term cryopreserved PBMCs can be partly used as biological resources for clinical research or basic studies, but the effect of cryopreservation on PBMCs should be considered when selecting cell samples, especially in research relating to activating or inhibiting function.
Azacytidine arrests ripening in cultivated strawberry (Fragaria × ananassa) by repressing key genes and altering hormone contents
Authors: Martínez-Rivas Félix Juan , Blanco-Portales Rosario , Molina-Hidalgo Francisco Javier , Caballero José Luis , Perez de Souza Leonardo , Alseekh Saleh , Fernie Alisdair R. , Muñoz-Blanco Juan , Rodríguez-Franco Antonio
Published: June 2022

Background

Strawberry ripening involves a number of irreversible biochemical reactions that cause sensory changes through accumulation of sugars, acids and other compounds responsible for fruit color and flavor. The process, which is strongly dependent on methylation marks in other fruits such as tomatoes and oranges, is highly controlled and coordinated in strawberry.

Results

Repeated injections of the hypomethylating compound 5-azacytidine (AZA) into green and unripeFragaria×ananassareceptacles fully arrested the ripening of the fruit. The process, however, was reversible since treated fruit parts reached full maturity within a few days after AZA treatment was stopped. Transcriptomic analyses showed that key genes responsible for the biosynthesis of anthocyanins, phenylpropanoids, and hormones such as abscisic acid (ABA) were affected by the AZA treatment. In fact, AZA downregulated genes associated with ABA biosynthetic genes but upregulated genes associated with its degradation. AZA treatment additionally downregulated a number of essential transcription factors associated with the regulation and control of ripening. Metabolic analyses revealed a marked imbalance in hormone levels, with treated parts accumulating auxins, gibberellins and ABA degradation products, as well as metabolites associated with unripe fruits.

Conclusions

AZA completely halted strawberry ripening by altering the hormone balance, and the expression of genes involves in hormone biosynthesis and degradation processes. These results contradict those previously obtained in other climacteric and fleshly fruits, where AZA led to premature ripening. In any case, our results suggests that the strawberry ripening process is governed by methylation marks.
Accuracy and influencing factors of the Field Triage Decision Scheme for adult trauma patients at a level-1 trauma center in Korea
Authors: Kang Byung Hee , Jung Kyoungwon , Kim Sora , Youn So Hyun , Song Seo Young , Huh Yo , Chang Hyuk-Jae
Published: June 2022

Background

We evaluated the accuracy of the prehospital Field Triage Decision Scheme, which has recently been applied in the Korean trauma system, and the factors associated with severe injury and prognosis at a regional trauma center in Korea.

Methods

From 2016 to 2018, prehospital data of injured patients were obtained from the emergency medical services of the national fire agency and matched with trauma outcomes at our institution. Severe injury (Injury Severity Score > 15), overtriage/undertriage rate, positive predictive value, negative predictive value, and accuracy were reviewed according to the triage protocol steps. A multivariate logistic regression analysis was performed to identify influencing factors in the field triage.

Results

Of the 2438 patients reviewed, 853 (35.0%) were severely injured. The protocol accuracy was as follows: step 1, 72.3%; step 2, 65.0%; step 3, 66.2%; step 1 or 2, 70.2%; and step 1, 2, or 3, 66.4%. Odds ratios (OR) (95% confidence interval [CIfor systolic blood pressure < 90 mmHg (3.535 [1.920–6.509]; p < 0.001), altered mental status (17.924 [8.980–35.777]; p < 0.001), and pedestrian injuries (2.473 [1.339–4.570], p = 0.04) were significantly associated with 24-h mortality. Penetrating torso injuries (7.108 [4.108–12.300]; p < 0.001); two or more proximal long bone fractures (4.134 [2.316–7.377]); p < 0.001); crushed, degloved, and mangled extremities (8.477 [4.068–17.663]; p < 0.001); amputation proximal to the wrist or ankle (42.964 [5.764–320.278]; p < 0.001); and fall from height (2.141 [1.497–3.062]; p < 0.001) were associated with 24-h surgical intervention.

Conclusion

The Korean field triage protocol is not yet accurate, with only some factors reflecting injury severity, making reevaluation necessary.
Decreasing boarders in the emergency department by reducing clerical work in the discharge process of in-hospital patients in Brazil – an interrupted time-series analysis
Authors: Moroço Diego Marques , Pazin-Filho Antonio
Published: June 2022

Background

Emergency Department (ED) boarding is related to in-hospital patients' discharge since no beds will be available for receiving ED patients if there is a delay for patients in the yard leaving the hospital. New techniques implemented in hospital institutions, such as digital signatures to facilitate clerical work improve these processes. We evaluated the impact of expediting patients' discharge after medical orders with the number of patients with an unplanned hospital admission from the Hospital Out Clinic directed to ED for waiting for an available bed in a public tertiary hospital in Brazil.

Methods

We conducted a quasi-experimental study before and after an intervention. It consisted of an encrypted digital signature to reduce clerical work and expedite the patient's release from the institution after medical discharge. We used an interrupted time-series analysis based on administrative data (number of hospital discharges, bed turnover, the time between medical discharge, and the time the patient effectively left the hospital) from 2011 to 2020.

Results

We enrolled 210,496 patients admitted to the hospital from January 2011 to December 2020. Of those, 69,897(33%) composed the group after the intervention. There was no difference between the groups' gender, age distribution, the proportion of surgical patients, or in-hospital stay (≤ 7 or > 7 days). The interrupted time series analysis for the time from medical order to effectively hospital discharge showed an immediate change in level (Coefficient β2 -3.6 h—95% confidence interval -3.9;-3.4), but no a difference in the slope of the behavior of the post-intervention curve (β3 0.0005 coefficient—95% confidence interval -0.0040;0.0050). For the number of patients directed to ED, we observed no immediate change in level (Coefficient β2 -0.84 patients—95% confidence interval -0.33;0.16), but a difference in the slope of the behavior of the post-intervention curve (β3 0.0005 coefficient—95% confidence interval -0.0040;0.0050).

Conclusion

Reducing clerical work and expediting patient discharge was associated with decreased potential boarders to ED.
Household and social characteristics associated with COVID-19 vaccine intent among Latino families in the San Francisco Bay Area
Authors: Wojcicki Janet M. , Escobar Milagro , Mendez Andrea DeCastro , Martinez Suzanna M.
Published: June 2022

Background

Latinos have had higher case counts, hospitalization rates and deaths during the COVID-19 pandemic nationally and in the state of California. Meanwhile, Latino vaccination rates remain lower than those of non-Hispanic Whites. COVID-19 vaccine nonintent, defined as intent to not vaccinate against COVID-19, among Latino individuals continues to be an issue in the state of California.

Methods

Families from three Latino longitudinal mother–child cohorts previously recruited in the San Francisco Bay Area were surveyed telephonically from February to June 2021 to assess attitudes towards vaccination against COVID-19 and prior vaccination, in general, for themselves and their children. Risk for vaccine nonintent was assessed using the Mann–Whitney rank sum non-parametric test for continuous predictors and chi-squared tests for categorical ones.

Results

Three hundred and nineteen families were surveyed from the Telomere at Birth (TAB), Hispanic Eating and Nutrition (HEN) and Latino Eating and Diabetes Cohort (LEAD). Approximately 36% from TAB and 28% from HEN/LEAD indicated COVID-19 vaccine nonintent for themselves and/or their children. Risk factors for vaccine nonintent included lower maternal age (p = 0.01), concern about vaccine side effects (p < 0.01) and prior history of a household members being infected with SARS-CoV-2 (p < 0.01) and indexes of household crowding including number of people sharing a bathroom (p = 0.048). Vaccine intent was also associated with receiving vaccine input from friends (p = 0.03), family (p < 0.01) and/or coworkers (p = 0.02) compared with those who were not planning on getting vaccinated against COVID-19.

Conclusions

Latino families living in crowded living situations who may not have received any COVID-19 advice from family, coworkers or friends are at particular risk for nonintent for vaccinatation against COVID-19. Community-based grassroots or promotor/a based interventions centered on trusted individuals with close community ties and counseling concerning vaccination against COVID-19 could help boost vaccination rates in this population group.
Early neurological deterioration in acute ischemic stroke patients after intravenous thrombolysis with alteplase predicts poor 3-month functional prognosis - data from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMS-China)
Authors: Che Fengli , Wang Anxin , Ju Yi , Ding Yarong , Duan Honglian , Geng Xiaokun , Zhao Xingquan , Wang Yongjun
Published: June 2022

Background

We aimed to investigate the risk factors of early neurological deterioration (END) after intravenous thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) and the relationship between END and poor 3-month functional outcomes.

Methods

Patients who accepted intravenous recombinant rt-PA were enrolled continuously. END was defined as an increase in National Institute of Health Stroke (NIHSS) score ≥ 4 points or death within 24 hours after intravenous thrombolysis. The modified Rankin Scale (mRS) score was recorded to evaluate the functional outcome of stroke, and the poor 3-month prognosis was defined as an mRS score ≥ of 3. Univariate and multivariate analyses were used to analyze the risk factors of END. The relation between END and 3-month functional outcome was analyzed by multivariate logistic regression analysis.

Results

A total of 1107 patients (mean age, 63.42 ± 11.33 years; 673 males) were included in the final analysis, and 81(7.32%) patients had END. In multivariate analysis, the serum glucose level was significantly associated with END; the odds ratio was 1.10 (95% CI 1.03 to 1.18, p = 0.004). The multivariate logistic analysis showed END has a notable association with the poor 3-month functional recovery even after adjusting for confounding factors; the adjusted OR was 8.25 (95% CI 3.77 to 18.03, p < 0.0001).

Conclusions

The initial serum glucose level might be an independent risk factor of END, and END might predict a poor 3-month prognosis.
Multidisciplinary treatment of retroperitoneal ectopic pregnancy: a case report and literature review
Authors: Xu Hainan , Cheng Dali , Yang Qing , Wang Dandan
Published: June 2022

Background

Retroperitoneal ectopic pregnancy (REP) is an extremely rare type of ectopic pregnancy, with a total of less than 32 cases reported in the English literature. Early diagnosis of REP is very difficult and all treatments entail a high risk of life-threatening complications.

Case presentation

A 29-year-old nulliparous woman presented a history of 50-day amenorrhea and 7-day upper abdominal pain without vaginal spotting. The serum beta-human chorionic gonadotropin (β-hCG) value was 65,004 m-international units per milliliter (mIU/mL), but no intrauterine gestational sac was found via transvaginal sonography (TVS). Then transabdominal ultrasonography (TAS) and abdominal contrast-enhanced computer tomography (CT) identified a retroperitoneal ectopic pregnancy (REP) tightly adjacent to the inferior vena cava and the abdominal aorta. After consultation from a multidisciplinary team, systemic methotrexate (MTX, intramuscular 20 mg daily for 5 consecutive days) combined with ultrasound-guided local potassium chloride solution injection into the gestational sac was scheduled firstly for the patient. However, serum β-hCG continued to increase and the patient experienced worsening abdominal pain. Laparotomy was performed jointly by a gynecologist and a vascular surgeon. During the operation, the gestational sac with fetal bud measuring about 4.5 × 4.0x3.0 cm, tightly adherent to the surface of inferior vena cava and the left side of abdominal aorta, was carefully dissociated out from the surrounding tissues and removed en bloc. Histopathology examination confirmed the diagnosis of REP. The patient recovered uneventfully and her serum β-hCG returned to normal range on the 23th postoperative day.

Conclusions

Considering the possibility of REP and combined radiological examinations, such as ultrasonography and CT, are crucial for the early diagnosis of this rare condition. A multidisciplinary team is necessary to treat REP.
T-DM1 efficacy in trastuzumab-pertuzumab pre-treated HER2 positive metastatic breast cancer patients: a meta-analysis
Authors: Omarini Claudia , Piacentini Federico , Sperduti Isabella , Cerma Krisida , Barbolini Monica , Canino Fabio , Nasso Cecilia , Isca Christel , Caggia Federica , Dominici Massimo , Moscetti Luca
Published: June 2022

Background

Current guidelines consider T-DM1 the standard 2nd line therapy for HER2 positive metastatic breast cancer (MBC) patients following trastuzumab (T) + pertuzumab (P) and taxane 1st line treatment. Despite this, there are no prospective studies supporting this sequence.

Methods

We performed a meta-analysis using real world data to determine the efficacy of T-DM1 after 1st line TP in HER2 positive MBC patients. We used a random-effect model to find differences in the rate of 1-year progression free survival (PFS) between TP pre-treated population and the EMILIA phase III pivotal trial.

Results

Seven studies were eligible. The meta-analysis showed a combined 1-year PFS risk difference for T-DM1 efficacy after TP in 2nd or more lines of -0.122, with lower and upper limits of -0.253 and 0.010, respectively (p = 0.07), with low heterogeneity among studies (I2 0.01%, p = 0.836). Considering the four studies on T-DM1 in 2nd line setting, 1-year PFS risk was -0.034 (95% CI -0.207 – 0,139; p = 0.701) (I2 0.01%, p = 0.91).

Conclusion

Overall, the efficacy of T-DM1 after TP seems to be similar to that previously reported in the EMILIA trial. In the second line setting, data are not mature enough to confirm T-DM1 efficacy in TP pre-treated population.
Potential prognosis index for m6A-related mRNA in cholangiocarcinoma
Authors: Zhu Huaqiang , Zhao Haini , Wang Jianlu , Zhao Shuchao , Ma Chaoqun , Wang Dongliang , Gao Hengjun , Yang Faji , Ni Qingqiang , Li Hongguang , Zhou Xu , Zhang Chunqing , Lu Jun
Published: June 2022

Background

Cholangiocarcinoma (CHOL) is a malignant tumor that originates in the extrahepatic bile duct and can extend from the hilar region to the lower end of the common bile duct. The prognosis of CHOL patients is particularly poor; therefore, in this study, we screened mRNAs correlated with N6-methyladenosine (m6A) to construct a risk model for prognosis in CHOL.

Methods

The TCGA-CHOL dataset was applied to obtain and analyze the coexpression of 1281 m6A-related mRNAs, from which 14 were selected for further analysis through univariate proportional hazards (cox) regression analysis. Aryl hydrocarbon receptor interacting protein (AIP), CCAAT/enhancer binding protein beta (CEBPB), syndecan1 (SDC1), vacuolar protein sorting 25 homolog (VPS25) and syntaxin binding protein 2 (STXBP2) were then screened out through the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis to develop a precise m6A-related mRNA prognosis risk model (MRMRPM) with an area under curve (AUC) of 0.908 and 0.923 after 1 and 2 years, respectively. We divided the samples into high-risk and low-risk groups using the m6A-related mRNA prognosis risk model.

Results

Kaplan–Meier analysis indicated poor overall survival (OS) for the high-risk group. Two Gene Expression Omnibus (GEO) datasets (GSE89748 and GSE107943) were used to validate the risk model. The results of drug sensitivity and immune cell infiltration analysis showed that the risk model could serve as a prognosis index of potential immunotherapeutic characteristics and drug sensitivity. Furthermore, the proportion of resting dendritic cells and regulatory T cells was positively associated with an increased expression of four m6A-related mRNAs — AIP, CEBPB, SDC1, and VPS25 — in the high-risk CHOL group.

Conclusions

Our findings suggest that this model can be a prognostic indicator for CHOL patients.
Suboptimal use of hormonal therapy among German men with localized high-risk prostate Cancer during 2005 to 2015: analysis of registry data
Authors: Abera Semaw Ferede , Bedir Ahmed , Glowka André , Vordermark Dirk , Medenwald Daniel
Published: June 2022

Background

This study assesses the use of hormonal therapy to treat high-risk localized prostate cancer (HRLPCa) cases diagnosed between 2005 and 2015.

Methods

All N0-XM0 with ≥T3a, or PCa cases with poorly differentiated feature (equivalent to Gleason score ≥ 8), diagnosed between 2005 and 2015 were extracted from German population-based cancer registries. Cases treated by surgery or chemotherapy were excluded. Description of hormonal therapy use by HRLPCa cases’ profile was presented. Relative risk (RR) was computed with a log-link function to identify factors associated with hormonal therapy use among radiotherapy-treated HRLPCa cases.

Results

A total of 5361 HRLPCa cases were analyzed. Only 27.6% (95% confidence interval [CI]: 26.4–28.8%) of the HRLPCa cases received hormonal therapy in combination with radiotherapy. The use of combined hormonal therapy and radiotherapy varied from 19.8% in Saxony to 47.8% in Schleswig-Holstein.

Application of hormonal therapy was higher for the locally advanced cases compared to the poorly differentiated cases (relative risk [RR] = 1.28; 95%CI: 1.19, 1.37). Older patients showed a slightly increased use of hormonal therapy (RR for a 10-year age increase = 1.09; 95%CI: 1.02, 1.16). Compared to PCa cases from the most affluent residential areas, cases from the least affluent (RR = 0.71; 95%CI: 0.55, 0.92) and medium (RR = 0.75; 95%CI: 0.58, 0.96) areas had decreased use of hormonal therapy. The introduction of the German S3-guideline did not make a marked difference in the uptake of both hormonal therapy and radiotherapy (RR = 1.02; 95%CI: 0.95, 1.09).

Conclusion

This study found a low use of hormonal therapy among HRLPCa patients treated without surgery. The introduction of the German S3-guideline for prostate cancer treatment does not seem to have impacted hormonal therapy use.
An iron metabolism and immune related gene signature for the prediction of clinical outcome and molecular characteristics of triple-negative breast cancer
Authors: Li Xiao-Fen , Fu Wen-Fen , Zhang Jie , Song Chuan-Gui
Published: June 2022

Background

An imbalance of intracellular iron metabolism can lead to the occurrence of ferroptosis. Ferroptosis can be a factor in the remodeling of the immune microenvironment and can affect the efficacy of cancer immunotherapy. How to combine ferroptosis-promoting modalities with immunotherapy to suppress triple-negative breast cancer (TNBC) has become an issue of great interest in cancer therapy. However, potential biomarkers related to iron metabolism and immune regulation in TNBC remain poorly understand.

Methods

We constructed an optimal prognostic TNBC-IMRGs (iron metabolism and immune-related genes) signature using least absolute shrinkage and selection operator (LASSO) cox regression. Survival analysis and ROC curves were analyzed to identify the predictive value in a training cohort and external validation cohorts. The correlations of gene signature with ferroptosis regulators and immune infiltration are also discussed. Finally, we combined the gene signature with the clinical model to construct a combined model, which was further evaluated using a calibration curve and decision curve analysis (DCA).

Results

Compared with the high-risk group, TNBC patients with low-risk scores had a remarkably better prognosis in both the training set and external validation sets. Both the IMRGs signature and combined model had a high predictive capacity, 1/3/5- year AUC: 0.866, 0.869, 0.754, and 1/3/5-yaer AUC: 0.942, 0.934, 0.846, respectively. The calibration curve and DCA also indicate a good predictive performance of the combined model. Gene set enrichment analysis (GSEA) suggests that the high-risk group is mainly enriched in metabolic processes, while the low-risk group is mostly clustered in immune related pathways. Multiple algorithms and single sample GSEA further show that the low-risk score is associated with a high tumor immune infiltration level. Differences in expression of ferroptosis regulators are also observed among different risk groups.

Conclusions

The IMRGs signature based on a combination of iron metabolism and immune factors may contribute to evaluating prognosis, understanding molecular characteristics and selecting treatment options in TNBC.
Rationale and design of ON-TRK: a novel prospective non-interventional study in patients with TRK fusion cancer treated with larotrectinib
Authors: Yang James C. H. , Brose Marcia S. , Castro Gilberto , Kim Edward S. , Lassen Ulrik N. , Leyvraz Serge , Pappo Alberto , López-Ríos Fernando , Reeves John A. , Fellous Marc , Penault-Llorca Frédérique , Rudzinski Erin R. , Tabatabai Ghazaleh , Vassal Gilles , Drilon Alexander , Trent Jonathan
Published: June 2022

Background

Tropomyosin receptor kinase (TRK) fusion proteins resulting from neurotrophic tyrosine receptor kinase (NTRK) gene fusions are rare primary oncogenic drivers in a wide array of tumors. Larotrectinib is a first-in-class, highly selective, central nervous system-active TRK inhibitor approved by the US Food and Drug Administration (FDA), European Medicines Agency (EMA), and over 40 countries for the treatment of TRK fusion solid tumors in adult and pediatric patients. Due to the rarity of TRK fusion cancer, larotrectinib was granted accelerated approval based on a relatively small number of patients enrolled in three early phase trials. ON-TRK aims to evaluate the safety profile of larotrectinib in a broader population and over extended time periods.

Methods

ON-TRK is a prospective, non-interventional, open-label, multicenter, multi-cohort, post-approval study in adult and pediatric patients with locally advanced or metastatic TRK fusion cancer treated with larotrectinib that will describe the safety and effectiveness of larotrectinib in real-world practice conditions. Adult patients will be grouped by tumor type and followed for at least 2 years. Patients < 18 years old will be enrolled under a ‘pediatric’ cohort regardless of tumor type and will be followed for 5 years to evaluate the risk of potential long-term adverse effects of larotrectinib on their growth and development. The effectiveness of larotrectinib in the overall study population as well as in patient subgroups will also be evaluated. Procedures avoided in patients with infantile fibrosarcoma (e.g., amputation) and the number of patients who were able to undergo surgery with a curative intent (excluding amputation) because of the use of larotrectinib will be described. Larotrectinib treatment patterns in real-world practice, including dosing and duration of treatment, will be described.

Discussion

The FDA Accelerated Approval Program allows for earlier approval of and patient access to drugs that treat serious conditions and fill an unmet medical need. This study is designed to fulfill post-approval requirements set by the FDA as well as post-marketing requirements set forth by local regulatory bodies and is part of the risk management plan for the EMA.

Study registration

This study is registered at ClinicalTrials.gov (NCT04142437).

Protocol version

v2.5, 25 March 2021.
Predictors for elevation of Intraocular Pressure (IOP) on glaucoma patients; a retrospective cohort study design
Authors: Birhanu Getasew , Tegegne Awoke Seyoum
Published: June 2022

Objective

Because of the increase in the number of cases, currently, glaucoma is a significant public health issue that it leads to optic nerve damage and vision loss. High Intraocular Pressure reading indicates that the treatment given to a glaucoma patient is not sufficient/ adequate. Hence, the elevation of intraocular pressure is one of the indicators that, the therapy given to glaucoma patients under treatment is inadequate. Therefore, the main objective of the current study was to investigate predictors for the variation of elevation of IOP readings on glaucoma patients.

Materials and methods

A retrospective cohort study design was conducted on 1254 glaucoma patients, whose followed-ups were from September 2015 to August 2016 at Felege Hiwot Teaching and Specialized Hospital, North West Ethiopia. Data analysis was conducted using Statistical Analysis of Systems (SAS) software version 9.2 and AMOS software. The parameter estimation was conducted using the maximum likelihood estimation technique.

Results

Main effects like age (β = 0.01, t-value = 0.15, p-value = 0.018), patients with normal blood pressure (β = -3.35, t-value = -2.28, p-value = 0.0263), patients without diabetics (β = -3.79, t-value = -2.47, p-value = 0.014), visiting times (β = -6.00, t-value = -5.02, p-value = 0.0001), farmer glaucoma patients (β = -6.04, t-value = 3.87, p-value = 0.0001) had significant and indirect effect for the variation of elevation of IOP on glaucoma patients. Interaction effects like visiting time with existence of diabetes, visiting time with cataract surgery significantly effected on the variable of interest. Hence, both main and interaction effects had significant effects on the variable of interest.

This study had identified socio-demographic characteristics, personal/individual behaviors, and clinical factors for the variation of elevation of IOP. The findings, in the current investigation, help health staff to conduct health-related education for awareness creation. Health-related education, about the progression of glaucoma, should be conducted on patients.