bluuebunny/crossref_metadata_2025 huggingface dataset:
Social and physical factors related to depression in the older population of Siberia, Russia: a cross-sectional study
Authors: von Fingerhut Georg , Mizukami Katsuyoshi , Yam Dorothy , Makarov Konstantin , Kim Yuriy , Kondyurina Elena , Yakovleva Lyudmila
Published: April 2021

Background

Depression and suicide rates are relatively high in the colder regions of Russia. Older individuals in these regions are especially susceptible to these issues and are understudied in this regard. This study aims to better understand the current depression prevalence, and the factors related to depression, among the older individuals in these colder regions of Russia by studying a population in Novosibirsk oblast.

Methods

A questionnaire survey was administered to 422 older individuals, assessing basic attributes and health status, and employing the following standardized scales: 8-item Short-Form Health Survey, Pittsburgh Sleep Quality Index, and 15-item Geriatric Depression Scale (GDS). Participants were divided in two groups (GDS ≤ 6, GDS > 6) and compared, using Student’s t test, χ2 test, and logistic regression analysis.

Results

Young old (YO) adults showed significant correlation of depression with asthma (P = 0.005, OR = 6.40, 95%CI: 1.74–23.5), having a spouse (P = 0.016, OR = 1.99, 95%CI: 1.14–3.48), and daily communication with others (P < 0.001, OR = 0.336, 95%CI: 0.197–0.572). Among old old (OO) adults, significant correlation with depression was found for the variables work status (P = 0.047, OR = 0.115, 95%CI: 0.014–0.974), and weekly walking (P = 0.014, OR = 0.288, 95%CI: 0.106–0.778).

Conclusions

Twenty eight percent of the participants have depression. In YO adults, frequent communication and social ties with individuals outside of the family can mitigate depression prevalence. As for OO adults, the factors that have the highest impact on mitigating depression are related to daily activity, including both frequent walking and working or self-employment. Asthma patients are one of the more sensitive groups towards depression, but further research on this topic is needed.
Five long non-coding RNAs establish a prognostic nomogram and construct a competing endogenous RNA network in the progression of non-small cell lung cancer
Authors: Yu Yong , Ren Kaiming
Published: April 2021

Background

Accumulating evidence has revealed that long non-coding RNAs (lncRNAs) play vital roles in the progression of non-small cell lung cancer (NSCLC). But the relationship between lncRNAs and survival outcome of NSCLC remains to be explored. Therefore, we attempt to figure out their survival roles and molecular connection in NSCLC.

Methods

By analyzing the transcriptome profiling of NSCLC from TCGA databases, we divided patients into three groups, and identified differentially expressed lncRNAs (DELs) of each group. Next, we explored the prognostic roles of common DELs by univariate and multivariate Cox analysis, Lasson, and Kaplan-Meier analysis. Additionally, we assessed and compared the prognostic accuracy of 5 lncRNAs through ROC curves and AUC values. Ultimately, we detected their potential function by enrichment analysis and molecular connection through establishing a competing endogenous RNA (ceRNA) network.

Results

One hundred ninety-seven common DELs were spotted. And we successfully screened out 5 lncRNAs related to the patient’s survival, including LINC01833, AC112206.2, FAM83A-AS1, BANCR, and HOTAIR. Combing with age and AJCC stage, we constructed a nomogram that prognostic prediction was superior to the traditional parameters. Furthermore, 275 qualified mRNAs related to 5 lncRNAs were spotted. Functional analysis indicates that these lncRNAs act key roles in the progression of NSCLC, such as P53 and cell cycle signaling pathway. And ceRNA network also suggests that these lncRNAs are tightly connected with tumor progression.

Conclusions

A nomogram and ceRNA network based on 5 lncRNAs indicate that there can effectively predict the overall survival of NSCLC and potentially serve as a therapeutic guide for NSCLC.
Irrational use of antibiotics in Iran from the perspective of complex adaptive systems: redefining the challenge
Authors: Sharif Zahra , Peiravian Farzad , Salamzadeh Jamshid , Mohammadi Nastaran Keshavarz , Jalalimanesh Ammar
Published: April 2021

Background

Irrational use of antibiotics is proving to be a major concern to the health systems globally. This results in antibiotics resistance and increases health care costs. In Iran, despite many years of research, appreciable efforts, and policymaking to avoid irrational use of antibiotics, yet indicators show suboptimal use of antibiotics, pointing to an urgent need for adopting alternative approaches to further understand the problem and to offer new solutions. Applying the Complex Adaptive Systems (CAS) theory, to explore and research health systems and their challenges has become popular. Therefore, this study aimed to better understand the complexity of the irrational use of antibiotics in Iran and to propose potential solutions.

Method

This research utilized a CAS observatory tool to qualitatively collect and analyse data. Twenty interviews and two Focus Group discussions were conducted. The data was enriched with policy document reviews to fully understand the system. MAXQDA software was used to organize and analyze the data.

Result

We could identify several diverse and heterogeneous, yet highly interdependent agents operating at different levels in the antibiotics use system in Iran. The network structure and its adaptive emergent behavior, information flow, governing rules, feedback and values of the system, and the way they interact were identified. The findings described antibiotics use as emergent behavior that is formed by an interplay of many factors and agents over time. According to this study, insufficient and ineffective interaction and information flow regarding antibiotics between agents are among key causes of irrational antibiotics use in Iran. Results showed that effective rules to minimize irrational use of antibiotics are missing or can be easily disobeyed. The gaps and weaknesses of the system which need redesigning or modification were recognized as well.

Conclusion

The study suggests re-engineering the system by implementing several system-level changes including establishing strong, timely, and effective interactions between identified stakeholders, which facilitate information flow and provision of on-time feedback, and create win-win rules in a participatory manner with stakeholders and the distributed control system.
No changes in adolescent’s sedentary behaviour across Europe between 2002 and 2017
Authors: López-Fernández J. , López-Valenciano A. , Mayo X. , Liguori G. , Lamb M. A. , Copeland R. J. , Jiménez A.
Published: April 2021

Background

Public health organizations have been alerted to the high levels of sedentary behaviour (SB) among adolescents as well as to the health and social consequences of excess sedentary time. However, SB changes of the European Union (EU) adolescents over time have not been reported yet. This study aimed to identify SB of the EU adolescents (15–17 years) in four-time points (2002, 2005, 2013 and 2017) and to analyse the prevalence of SB according to the sex.

Methods

SB of 2542 adolescents (1335 boys and 1207 girls) as a whole sample and country-by-country was analysed in 2002, 2005, 2013, and 2017 using the Sport and Physical Activity EU Special Eurobarometers’ data. SB was measured using the sitting time question from the short version of the International Physical Activity Questionnaire (IPAQ), such that 4h30min of daily sitting time was the delineating point to determine excess SB behaviour (≥4h30min of sitting time) or not (≤4h30min of sitting time). A χ2 test was used to compare the prevalence of SB between survey years. Furthermore, SB prevalence between sexes was analysed using a Z-Score test for two population proportions.

Results

The prevalence of SB among EU adolescents across each of the four survey years ranged from 74.2 and 76.8%, rates that are considered high. High levels of SB were also displayed by both sexes (girls: 76.8 to 81.2%; boys: 71.7 to 76.7%). No significant differences in the prevalence of SB among years (p > 0.05) were found for the whole sample, and for either girls or boys. Also, no significant differences in the prevalence of SB between girls and boys were found.

Conclusion

The SB prevalence in European adolescents is extremely high (76.8% in 2017) with no differences between girls and boys. No significant improvements have been seen between 2002 and 2017. Eurobarometer should increase the adolescents’ sample to make possible benchmarking comparisons among the EU countries and extend the survey to the younger children population.
Development and internal validation of a prediction model of prostate cancer on initial transperineal template-guided prostate biopsy
Authors: Chen Yuliang , Zhou Zhien , Zhou Yi , Wu Xingcheng , Xiao Yu , Ji Zhigang , Li Hanzhong , Yan Weigang
Published: April 2021

Background

Due to the invasiveness of prostate biopsy, a prediction model of the individual risk of a positive biopsy result could be helpful to guide clinical decision-making. Most existing models are based on transrectal ultrasonography (TRUS)-guided biopsy. On the other hand, transperineal template-guided prostate biopsy (TTPB) has been reported to be more accurate in evaluating prostate cancer. The objective of this study is to develop a prediction model of the detection of high-grade prostate cancer (HGPC) on initial TTPB.

Result

A total of 1352 out of 3794 (35.6%) patients were diagnosed with prostate cancer, 848 of whom had tumour with Grade Group 2–5. Age, PSA, PV, DRE and f/t PSA are independent predictors of HGPC with p < 0.001. The model showed good discrimination ability (c-index 0.886) and calibration during internal validation and good clinical performance was observed through decision curve analysis. The external validation of CPCC-RC, an existing model, demonstrated that models based on TRUS-guided biopsy may underestimate the risk of HGPC in patients who underwent TTPB.

Conclusion

We established a prediction model which showed good discrimination ability and calibration in predicting the detection of HGPC by initial TTPB. This model can be used to aid clinical decision making for Chinese patients and other Asian populations with similar genomic backgrounds, after external validations are conducted to further confirm its clinical applicability.
Estimation of salivary matrix metalloproteinases- 12 (MMP- 12) levels among patients presenting with oral submucous fibrosis and oral squamous cell carcinoma
Authors: Saleem Zohra , Shaikh Abdul Hafeez , Zaman Uzma , Ahmed Shaheen , Majeed Muhammad Mansoor , Kazmi Anum , Farooqui Waqas Ahmed
Published: April 2021

Background

Oral squamous cell carcinoma is a global threat and accounts for approximately 90% of malignant oral lesions. The emergence of oral carcinoma is linked to precancerous lesions, which act as precursors of the disease. Matrix metalloproteinases appear to play a significant role in the pathogenesis of both precancerous conditions and oral malignancies due to their participation in remodeling of the extracellular matrix.

Methodology

This is an analytical study conducted at Dow University of Health Sciences, Pakistan. Unstimulated saliva samples were collected from healthy, oral submucous fibrosis and oral squamous cell carcinoma patients. The level of MMP-12 was estimated using enzyme-linked immunosorbent assay. One-way Analysis of variance was run to determine if MMP-12 levels differ between the three groups, which was preceded by post hoc Tuckey test. MMP-12 cut off values were determined using Receiver operating characteristic curve.

Results

A significant difference in salivary MMP-12 expression was observed in OSF and OSCC (p < 0.001). The expression of salivary MMP-12 was higher in OSF and OSCC patients as compared to the healthy group (p < 0.001). The mean MMP-12 expression in OSCC appeared higher than in OSF cases (p < 0.05). MMP-12 value of$$\ge$$≥4.05 ng/ml and$$\ge$$≥4.20 ng/ml is predictive of OSF and OSCC respectively, with 100% sensitivity and specificity (p < 0.001).

Conclusion

Increased expression of MMP-12 appears as the healthy patient advances to OSF and OSCC. The study results also demonstrate higher MMP-12 expression in OSCC patients as compared to OSF. Therefore, the estimation of salivary MMP-12 serves as a valuable non-invasive early diagnostic tool in diagnosing oral submucous fibrosis and oral squamous cell carcinoma.
Automatic glaucoma detection based on transfer induced attention network
Authors: Xu Xi , Guan Yu , Li Jianqiang , Ma Zerui , Zhang Li , Li Li
Published: April 2021

Background

Glaucoma is one of the causes that leads to irreversible vision loss. Automatic glaucoma detection based on fundus images has been widely studied in recent years. However, existing methods mainly depend on a considerable amount of labeled data to train the model, which is a serious constraint for real-world glaucoma detection.

Methods

In this paper, we introduce a transfer learning technique that leverages the fundus feature learned from similar ophthalmic data to facilitate diagnosing glaucoma. Specifically, a Transfer Induced Attention Network (TIA-Net) for automatic glaucoma detection is proposed, which extracts the discriminative features that fully characterize the glaucoma-related deep patterns under limited supervision. By integrating the channel-wise attention and maximum mean discrepancy, our proposed method can achieve a smooth transition between general and specific features, thus enhancing the feature transferability.

Results

To delimit the boundary between general and specific features precisely, we first investigate how many layers should be transferred during training with the source dataset network. Next, we compare our proposed model to previously mentioned methods and analyze their performance. Finally, with the advantages of the model design, we provide a transparent and interpretable transferring visualization by highlighting the key specific features in each fundus image. We evaluate the effectiveness of TIA-Net on two real clinical datasets and achieve an accuracy of 85.7%/76.6%, sensitivity of 84.9%/75.3%, specificity of 86.9%/77.2%, and AUC of 0.929 and 0.835, far better than other state-of-the-art methods.

Conclusion

Different from previous studies applied classic CNN models to transfer features from the non-medical dataset, we leverage knowledge from the similar ophthalmic dataset and propose an attention-based deep transfer learning model for the glaucoma diagnosis task. Extensive experiments on two real clinical datasets show that our TIA-Net outperforms other state-of-the-art methods, and meanwhile, it has certain medical value and significance for the early diagnosis of other medical tasks.
A comparative performance analysis of the International Classification of Functioning, Disability and Health and the Item-Perspective Classification framework for classifying the content of patient reported outcome measures
Authors: Rosa Derek , MacDermid Joy , Klubowicz Dorota
Published: April 2021

Background

Standardized coding of the content presented in patient reported outcome measures can be achieved using classification frameworks, and the resulting data can be used for ascertaining content validity or comparative analyses. The International Classification of Functioning (ICF) is a framework with a detailed conceptual structure that has been successfully utilized for such purposes through established coding procedures. The Item Perspective Classification (IPC) framework is a newly developed relational coding system that classifies the respondent perspective and conceptual domains addressed in items. The purpose of this study was to compare and describe the performance of these two frameworks when used alone, and in conjunction, for the generation of data pertaining to the content of patient reported outcome measures.

Methods

Six health-related quality of life questionnaires with a total of 159 items were classified by two raters using the Item Perspective Classification framework in conjunction with the International Classification of Functioning. Framework performance indicators included: classification capacity (percent of items amenable to successful classification), coding efficiency (number of codes required to classify items), and content overlap detection (percent of items sharing identical classification codes with at least one other item). Inter-rater reliability of item coding was determined using Krippendorff's alpha.

Results

Classification capacity of the IPC framework was 97%, coding efficiency 26, and content overlap detection was 95%; whereas respective values for the ICF were 68%, 114, and 58%. When used in conjunction values were 63%, 129, and 30%. Krippendorff's alpha exceeded 0.97 for all 3 classification indices.

Conclusion

Inter-rater agreement on classification data was excellent. The IPC framework provided a unique classification of the respondent’s judgment during item response and classified more items using fewer categories, indicated greater content overlap across items and was able to describe the relationship between multiple concepts presented within the context of a single item. The ICF provided a unique classification of item content relating to aspects of disability and generated more detailed and precise descriptions. A combined approach provided a rich description (detailed codes) with each framework providing complementary information. The benefits of this approach in instrument development and content validation require further investigation.
Clinicopathologic features of metastatic small cell carcinoma of the prostate to the liver: a series of four cases
Authors: Bell Phoenix D. , Huber Aaron R. , Agostini-Vulaj Diana
Published: April 2021

Background

Small cell neuroendocrine carcinoma of the prostate (SCNECP) is a rare, aggressive subtype of prostate carcinoma. Most SCNECP arise from conventional prostate adenocarcinoma (CPAC) treated with androgen deprivation therapy (ADT).

Case presentations

We identified four cases of CPAC treated with ADT, which evolved to SCNECP with liver metastasis. The average interval between the diagnosis of CPAC and SCNECP was 102 months (range: 12 to 168). Histologically, the tumors showed nests of cells with high nuclear:cytoplasmic ratios, granular chromatin, and frequent mitoses. All cases were synaptophysin, chromogranin, and AE1/AE3 positive, with a Ki-67 labeling index ≥70%. NKX3.1 was negative in all but one case and TTF-1 was positive in half. Weak ERG positivity by IHC was seen in one case which also demonstrated the TMPRSS2-ERG gene rearrangement; all other cases were negative for ERG by IHC. Serum prostate specific antigen (PSA) levels were normal to near-normal in all. The median interval between the diagnosis of SCNECP and death was 3.25 months (range: 0.75 to 26).

Conclusions

Our case series highlights the importance of considering a prostate primary, even in the setting of normal PSA levels and loss of prostate markers, when diagnosing neuroendocrine carcinoma in the liver. Further, we emphasize the significance of diagnosing SCNECP that metastasizes to the liver, as it portends a particularly dismal prognosis.
Perceptions of the barriers, facilitators, outcomes, and helpfulness of strategies to implement screening, brief intervention, and referral to treatment in acute care
Authors: Keen Alyson , Thoele Kelli , Oruche Ukamaka , Newhouse Robin
Published: April 2021

Background

Screening, Brief Intervention, and Referral to Treatment (SBIRT) is a clinical intervention used to address alcohol and illicit drug use. SBIRT use has resulted in positive health and social outcomes; however, SBIRT implementation remains low. Research on implementing interventions, such as SBIRT, lacks information about challenges and successes related to implementation. The Expert Recommendations for Implementing Change (ERIC) provides a framework to guide comprehension, clarity, and relevance of strategies available for implementation research. This framework was applied to qualitative feedback gathered from site coordinators (SCs) leading SBIRT implementation. The purpose of this study was to describe the SCs’ experiences pertaining to SBIRT implementation across a health system.

Methods

Within the context of a larger parent study, a semi-structured interview guide was used to capture 14 SCs’ perceptions of the barriers, facilitators, and outcomes pertaining to SBIRT implementation. Qualitative data were analyzed using standard content analytic procedures. A follow-up survey was developed based on 14 strategies identified from qualitative data and was administered electronically to determine the SC’s perceptions of the most helpful implementation strategies on a scale of 1 (least helpful) to 5 (most helpful).

Results

All 14 invited SCs participated in the SBIRT implementation interview, and 11 of 14 (79%) responded to the follow-up survey. Within the categories of barriers, facilitators, and outcomes, 25 subthemes emerged. The most helpful implementation strategies were reexamining the implementation (M = 4.38; n = 8), providing ongoing consultation (M = 4.13; n = 8), auditing and providing feedback (M = 4.1; n = 10), developing education materials (M = 4.1; n = 10), identifying and preparing champions (M = 4; n = 7), and tailoring strategies (M = 4; n = 7).

Conclusion

SCs who led implementation efforts within a large healthcare system identified several barriers and facilitators to the implementation of SBIRT. Additionally, they identified clinician-related outcomes associated with SBIRT implementation into practice as well as strategies that were helpful in the implementation process. This information can inform the implementation of SBIRT and other interventions in acute care settings.
G-quadruplexes are transcription factor binding hubs in human chromatin
Authors: Spiegel Jochen , Cuesta Sergio Martínez , Adhikari Santosh , Hänsel-Hertsch Robert , Tannahill David , Balasubramanian Shankar
Published: April 2021

Background

The binding of transcription factors (TF) to genomic targets is critical in the regulation of gene expression. Short, double-stranded DNA sequence motifs are routinely implicated in TF recruitment, but many questions remain on how binding site specificity is governed.

Results

Herein, we reveal a previously unappreciated role for DNA secondary structures as key features for TF recruitment. In a systematic, genome-wide study, we discover that endogenous G-quadruplex secondary structures (G4s) are prevalent TF binding sites in human chromatin. Certain TFs bind G4s with affinities comparable to double-stranded DNA targets. We demonstrate that, in a chromatin context, this binding interaction is competed out with a small molecule. Notably, endogenous G4s are prominent binding sites for a large number of TFs, particularly at promoters of highly expressed genes.

Conclusions

Our results reveal a novel non-canonical mechanism for TF binding whereby G4s operate as common binding hubs for many different TFs to promote increased transcription.
Clinical course, radiological findings and late outcome in preterm infant with suspected vertical transmission born to a mother with severe COVID-19 pneumonia: a case report
Authors: Farhadi Roya , Mehrpisheh Shahrokh , Ghaffari Vajiheh , Haghshenas Mohammadreza , Ebadi Aghdas
Published: April 2021

Background

Vertical transmission of coronavirus disease 2019 (COVID-19) from mother to newborn infant is doubtful, and very little is known about disease severity and neonatal outcome.

Case presentation

We present a preterm Iranian infant born to a Persian mother with severe COVID-19 pneumonia. The mother underwent cesarean delivery, and amniotic fluid yielded a positive result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by real-time reverse transcription polymerase chain reaction (RT-PCR). The newborn infant showed early-onset infection with SARS-CoV-2 confirmed on pharyngeal swabs by RT-PCR assay within 24 hours after birth, suggesting vertical transmission. Unfortunately, the mother died 14 days after delivery. We describe the clinical course and outcome of the infant up to 7 months of age.

Conclusion

COVID-19 infection in pregnant women may increase maternal morbidity, mortality and possibly vertical transmission in severe cases. However, it does not seem to progress to serious early or late neonatal complications.
Segmentation of epithelial human type 2 cell images for the indirect immune fluorescence based on modified quantum entropy
Authors: Hanaa Abu-Zinadah , Gamil Abdel Azim
Published: April 2021

The autoimmune disorders such as rheumatoid, arthritis, and scleroderma are connective tissue diseases (CTD). Autoimmune diseases are generally diagnosed using the antinuclear antibody (ANA) blood test. This test uses indirect immune fluorescence (IIf) image analysis to detect the presence of liquid substance antibodies at intervals the blood, which is responsible for CTDs. Typically human alveolar epithelial cells type 2 (HEp2) are utilized as the substrate for the microscope slides. The various fluorescence antibody patterns on HEp-2 cells permits the differential designation-diagnosis. The segmentation of HEp-2 cells of IIf images is therefore a crucial step in the ANA test. However, not only this task is extremely challenging, but physicians also often have a considerable number of IIf images to examine.In this study, we propose a new methodology for HEp2 segmentation from IIf images by maximum modified quantum entropy. Besides, we have used a new criterion with a flexible representation of the quantum image(FRQI). The proposed methodology determines the optimum threshold based on the quantum entropy measure, by maximizing the measure of class separability for the obtained classes over all the gray levels. We tested the suggested algorithm over all images of the MIVIA HEp 2 image data set.To objectively assess the proposed methodology, segmentation accuracy (SA), Jaccard similarity (JS), the F1-measure,the Matthews correlation coefficient(MCC), and the peak signal-to-noise ratio (PSNR) were used to evaluate performance. We have compared the proposed methodology with quantum entropy, Kapur and Otsu algorithms, respectively.The results show that the proposed algorithm is better than quantum entropy and Kapur methods. In addition, it overcomes the limitations of the Otsu method concerning the images which has positive skew histogram.This study can contribute to create a computer-aided decision (CAD) framework for the diagnosis of immune system diseases
Genetic mechanisms and correlated risk factors of antimicrobial-resistant ESKAPEE pathogens isolated in a tertiary hospital in Malaysia
Authors: Ngoi Soo Tein , Chong Chun Wie , Ponnampalavanar Sasheela Sri La Sri , Tang Soo Nee , Idris Nuryana , Abdul Jabar Kartini , Gregory Michael J. , Husain Tupur , Teh Cindy Shuan Ju
Published: April 2021

Background

Knowledge on the epidemiology, genotypic and phenotypic features of antimicrobial-resistant (AMR) ESKAPEE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., and Escherichia coli) and their association with hospital-acquired infections (HAIs) are limited in Malaysia. Therefore, we evaluated the AMR features and resistance mechanisms of the ESKAPEE pathogens collected in a tertiary hospital located in the capital of Malaysia.

Methods

A total of 378 AMR-ESKAPEE strains were obtained based on convenience sampling over a nine-month study period (2019–2020). All strains were subjected to disk diffusion and broth microdilution assays to determine the antimicrobial susceptibility profiles. Polymerase chain reaction (PCR) and DNA sequence analyses were performed to determine the AMR genes profiles of the non-susceptible strains. Chi-square test and logistic regression analyses were used to correlate the AMR profiles and clinical data to determine the risk factors associated with HAIs.

Results

High rates of multidrug resistance (MDR) were observed in A. baumannii, K. pneumoniae, E. coli, and S. aureus (69–89%). All organisms except E. coli were frequently associated with HAIs (61–94%). Non-susceptibility to the last-resort drugs vancomycin (in Enterococcus spp. and S. aureus), carbapenems (in A. baumannii, P. aeruginosa, and Enterobacteriaceae), and colistin (in Enterobacteriaceae) were observed. Both A. baumannii and K. pneumoniae harbored a wide array of extended-spectrum β-lactamase genes (blaTEM, blaSHV, blaCTX-M, blaOXA). Metallo-β-lactamase genes (blaVEB, blaVIM, blaNDM) were detected in carbapenem-resistant strains, at a higher frequency compared to other local reports. We detected two novel mutations in the quinolone-resistant determining region of the gyrA in fluoroquinolone-resistant E. coli (Leu-102-Ala; Gly-105-Val). Microbial resistance to ampicillin, methicillin, and cephalosporins was identified as important risk factors associated with HAIs in the hospital.

Conclusion

Overall, our findings may provide valuable insight into the microbial resistance pattern and the risk factors of ESKAPEE-associated HAIs in a tertiary hospital located in central Peninsular Malaysia. The data obtained in this study may contribute to informing better hospital infection control in this region.
Perspectives on eco-water security and sustainable development in the Yangtze River Basin
Authors: Xia Jun , Li Zhe , Zeng Sidong , Zou Lei , She Dunxian , Cheng Dandong
Published: April 2021

The Yangtze River, the largest river in China, has been facing major challenges in massive flooding and eco-environmental health over the past decades. Sustainable socioeconomic development in the Yangtze River Basin depends on water and ecosystem security. This overview addresses eco-water security under the changing environment of the Yangtze River Basin. Looking forward to a healthy Yangtze River in the future, there are still uncertainties regarding how to assess and wisely manage the Yangtze River through a systematic, integrated approach applied to multiple dimensions, water, biodiversity, ecological services, and resilience, for the sustainable development of ecosystems and human beings. The Yangtze Simulator, an integrated river basin model powered by artificial intelligence and interdisciplinary science, is introduced and discussed, and it will serve as a robust tool for good governance of the Yangtze River Basin.
Treating Acute Leukemia During the COVID-19 Pandemic in an Environment With Limited Resources: A Multicenter Experience in Four Latin American Countries
Authors: Demichelis-Gómez Roberta , Alvarado-Ibarra Martha , Vasquez-Chávez Jule , Delgado-López Nancy , Gómez-Cortés Cynthia , Espinosa-Bautista Karla , Cooke-Tapia Ana , Milán-Salvatierra Andrea , Gómez-De León Andrés , Lee-Tsai Yu Ling , Rosales-López Daniel , Cabrera-García Álvaro , Amador-Medina Fabián , Córdoba-Ramírez Alejandra , Murrieta-Álvarez Iván , Solís-Poblano Juan Carlos , Apodaca-Chávez Elia , Rangel-Patiño Juan , Álvarez-Vera José Luis , Arana-Luna Luara , De la Peña-Celaya José Antonio , Espitia-Ríos María Eugenia , Hernández-Ruiz Eleazar , Pérez-Zúñiga Juan Manuel , Peña-López Estefanía , González-Rivera Rosa , García-Leyva María Fernanda , Tejeda-Romero Mónica , Cruz-Rico Jorge , Balderas-Delgado Carolina , Ruíz-Argüelles Guillermo J. , Gómez-Almaguer David
Published: April 2021

PURPOSE

The COVID-19 pandemic is a colossal challenge for global health; nonetheless, specific subgroups face considerably higher risks for infection and mortality. Among patients with malignant diseases, those with hematologic neoplasms are at a higher risk for poor outcomes. The objective of this study was to register treatment modifications associated with the COVID-19 pandemic and their short-term consequences in Latin America.

METHODS

Multicenter, prospective, observational, cohort study including patients older than 14 years from 14 centers in four countries (Mexico, Peru, Guatemala, and Panama) who had a confirmed diagnosis of acute leukemia, and who were undergoing active treatment since the first COVID-19 case in each country until the cutoff on July 15, 2020.

RESULTS

We recruited 635 patients. Treatment modifications because of the COVID-19 pandemic were reported in 40.8% of cases. The main reason for such modifications was logistic issues (55.0%) and the most frequent modification was chemotherapy delay (42.0%). A total of 13.1% patients developed COVID-19 disease, with a mortality of 37.7%. Several factors were identified as independently associated with mortality, including a diagnosis of acute myeloid leukemia (odds ratio 2.38 [95% CI, 1.47 to 3.84]; P < .001), while the use of telemedicine was identified as a protective factor (odds ratio 0.36 [95% CI, 0.18 to 0.82]; P = .014).

CONCLUSION

These results highlight the collateral damage of COVID-19 in oncology patients.
Association of Germline BRCA Pathogenic Variants With Diminished Ovarian Reserve: A Meta-Analysis of Individual Patient-Level Data
Authors: Turan Volkan , Lambertini Matteo , Lee Dong-Yun , Wang Erica , Clatot Florian , Karlan Beth Y. , Demeestere Isabelle , Bang Heejung , Oktay Kutluk
Published: April 2021

PURPOSE

To determine whether germline BRCA (g BRCA) pathogenic variants are associated with decreased ovarian reserve.

MATERIALS AND METHODS

An individual patient-level data meta-analysis was performed using five data sets on 828 evaluable women who were tested for g BRCA. Of those, 250 carried g BRCA, whereas 578 had tested negative and served as controls. Of the women with g BRCA, four centers studied those affected with breast cancer (n = 161) and one studied unaffected individuals (n = 89). The data were adjusted for the center, age, body mass index, smoking, and oral contraceptive pill use before the final analysis. Anti-Müllerian hormone (AMH) levels in affected women were drawn before presystemic therapy.

RESULTS

The mean age of women with versus without g BRCA1/2 (34.1 ± 4.9 v 34.3 ± 4.8 years; P = .48) and with g BRCA1 versus g BRCA2 (33.7 ± 4.9 v 34.6 ± 4.8 years; P = .16) was similar. After the adjustments, women with g BRCA1/2 had significantly lower AMH levels compared with controls (23% lower; 95% CI, 4 to 38; P = .02). When the adjusted analysis was limited to affected women (157 with g BRCA v 524 without, after exclusions), the difference persisted (25% lower; 95% CI, 9 to 38; P = .003). The serum AMH levels were lower in women with g BRCA1 (33% lower; 95% CI, 12 to 49; P = .004) but not g BRCA2 compared with controls (7% lower; 95% CI, 31% lower to 26% higher; P = .64).

CONCLUSION

Young women with g BRCA pathogenic variants, particularly those affected and with g BRCA1, have lower serum AMH levels compared with controls. They may need to be preferentially counseled about the possibility of shortened reproductive lifespan because of diminished ovarian reserve.
Cognitive and Adaptive Functioning in Youth With Retinoblastoma: A Longitudinal Investigation Through 10 Years of Age
Authors: Willard Victoria W. , Qaddoumi Ibrahim , Pan Haitao , Hsu Chia-Wei , Brennan Rachel C. , Wilson Matthew W. , Rodriguez-Galindo Carlos , Goode Kristin , Parris Kendra , Phipps Sean
Published: April 2021

PURPOSE

To describe the trajectory of cognitive and adaptive functioning in pediatric patients with retinoblastoma from diagnosis through age 10. This is an extension of a previous report that discussed findings from diagnosis through age 5.

PATIENTS AND METHODS

Ninety-eight participants with retinoblastoma completed psychological assessments as part of their enrollment on an institutional treatment protocol, with 73 completing an additional assessment at age 10. Trajectories of adaptive and cognitive functioning were determined, with data analyzed by treatment strata, and patients with 13q- analyzed separately.

RESULTS

Longitudinal trajectories identified a significant change point in trends at age 5, with functioning declining from diagnosis through age 5 and then increasing from age 5 to age 10. This pattern was observed for all strata for adaptive functioning, but only for enucleation-only patients (strata C low) for cognitive functioning. Cognitive trajectories were also influenced by laterality and enucleation status. At age 10, overall functioning was generally within the average range, although estimated intelligence quotient was significantly below the normative mean for enucleation-only (C low) patients. Patients with 13q- demonstrated very low functioning, but few analyses were significant because of small sample size.

CONCLUSION

The results generally indicate that previously demonstrated declines in functioning from diagnosis through age 5 improve by age 10. However, these early declines, as well as the continuous difficulties observed in patients treated with enucleation only, suggest the need for early intervention services for young patients with retinoblastoma. Continuous monitoring of the psychological functioning of patients with retinoblastoma, increased awareness of risk factors such as unilateral disease, enucleation, race, and surgery-only treatment plans, and referral to Early Intervention for all patients are indicated.
Life-course Exposure to Perfluoroalkyl Substances in Relation to Markers of Glucose Homeostasis in Early Adulthood
Authors: Valvi Damaskini , Højlund Kurt , Coull Brent A , Nielsen Flemming , Weihe Pal , Grandjean Philippe
Published: April 2021

Objective

To investigate the prospective associations of life-course perfluoroalkyl substances (PFASs) exposure with glucose homeostasis at adulthood.

Methods

We calculated insulin sensitivity and beta-cell function indices based on 2-h oral glucose tolerance tests at age 28 in 699 Faroese born in 1986–1987. Five major PFASs were measured in cord whole blood and in serum from ages 7, 14, 22, and 28 years. We evaluated the associations with glucose homeostasis measures by PFAS exposures at different ages using multiple informant models fitting generalized estimating equations and by life-course PFAS exposures using structural equation models.

Results

Associations were stronger for perfluorooctane sulfonate (PFOS) and suggested decreased insulin sensitivity and increased beta-cell function—for example, β (95% CI) for log-insulinogenic index per PFOS doubling = 0.12 (0.02, 0.22) for prenatal exposures, 0.04 (−0.10, 0.19) at age 7, 0.07 (−0.07, 0.21) at age 14, 0.05 (−0.04, 0.15) at age 22, and 0.04 (−0.03, 0.11) at age 28. Associations were consistent across ages (P for age interaction > 0.10 for all PFASs) and sex (P for sex interaction > 0.10 for all PFASs, except perfluorodecanoic acid). The overall life-course PFOS exposure was also associated with altered glucose homeostasis (P = 0.04). Associations for other life-course PFAS exposures were nonsignificant.

Conclusions

Life-course PFAS exposure is associated with decreased insulin sensitivity and increased pancreatic beta-cell function in young adults.
Cardiovascular Neuroendocrinology: Emerging Role for Neurohypophyseal Hormones in Pathophysiology
Authors: Aikins Ato O , Nguyen Dianna H , Paundralingga Obed , Farmer George E , Shimoura Caroline Gusson , Brock Courtney , Cunningham J Thomas
Published: April 2021

Arginine vasopressin (AVP) and oxytocin (OXY) are released by magnocellular neurosecretory cells that project to the posterior pituitary. While AVP and OXY currently receive more attention for their contributions to affiliative behavior, this mini-review discusses their roles in cardiovascular function broadly defined to include indirect effects that influence cardiovascular function. The traditional view is that neither AVP nor OXY contributes to basal cardiovascular function, although some recent studies suggest that this position might be re-evaluated. More evidence indicates that adaptations and neuroplasticity of AVP and OXY neurons contribute to cardiovascular pathophysiology.
The use of an inhibitor of protein synthesis to investigate the roles of ecdysteroids and sex-determination genes on the expression of the genes encoding theDrosophilayolk proteins
Authors: Bownes Mary , Scott Ann , Blair Mairead
Published: April 2021

The three yolk-protein genes of Drosophila are normally expressed only in adult female fat bodies and ovaries. 20-hydroxyecdysone can affect the transcription of these genes in males and females, as can mutations in the sex-determining genes tra, tra-2, ix and dsx. We have asked a number of basic questions about how these genes are regulated, using an inhibitor of protein synthesis (cycloheximide), labelling RNA in vivo, a temperature-sensitive sex-determination mutant (tra-2tsl), and 20-hydroxyecdysone. We have found that the yolk-protein genes are continuously transcribed in the fat bodies of adult females and that maintenance of this transcription requires protein synthesis. Hormone induction in males is also inhibited by cycloheximide, suggesting that the products of other genes are essential both for 20-hydroxyecdysone to be able to switch on the genes, and for their continuous transcription in the female fat body. The products of the tra-2 gene are also required for continuous transcription of the yolk-protein genes, suggesting that the pathway inhibited by the cycloheximide is that of the sex-determination hierarchy. 20-hydroxyecdysone can override the sex-determination system and induce yolk protein synthesis in normal males and tra-2ts reared and maintained at the restrictive temperature.
Identification of incomplete coding sequences for steroid sulphatase on the human Y chromosome: evidence for an ancestral pseudoautosomal gene?
Authors: Fraser N. , Ballabio A. , Zollo M. , Persico G. , Craig I.
Published: April 2021

A cDNA clone (p422) containing about 200 bp of coding sequences for steroid sulphatase (STS) has been isolated from a λgt11 expression library by antibody screening and has been assigned by mapping with a somatic cell hybrid panel and by in situ hybridization to Xp22.3; a localization coincident with the previously identified locus for STS expression. Although no significant hybridization of this clone to the Y chromosome was observed, p422 has been used to isolate a longer cDNA clone and genomic sequences which do recognize Y-specific restriction fragments. An abbreviated STS gene has been localized to Yqll.2. The coding sequences for the human enzyme shows little homology to sequences in mice.
The role of F-actin in determining the division plane of carrot suspension cells. Drug studies
Authors: Lloyd Clive W. , Traas Jan A.
Published: April 2021

Following the report that a network of F-actin is associated with the nucleus throughout the division cycle, we have examined the involvement of F-actin in determining the division plane of carrot suspension cells. This was achieved by treating cells with drugs and then staining the unfixed cells with rhodaminyl lysine phallotoxin in detergent extraction buffer.

In interphase, actin cables radiate from the nucleus but at the cortex become more or less transversely arranged in the pattern already known for cortical microtubules. Concentration of the cortical F-actin into a band at preprophase draws most of the nucleus-associated actin into a transvacuolar disc, thereby forming the phragmosome within which mitosis and cytokinesis occur.

In addition to this transversely aligned structure, F-actin is also associated with the spindle poles during mitosis but these filaments tend to align at right angles to the phragmosomal actin. F-actin therefore defines transverse and longitudinal vectors as division approaches. Depolymerization of F-actin with cyto-chalasin D can cause the spindle axis to reorientate such that the pole-pole axis comes to lie, abnormally, parallel with the phragmosome.

The cytokinetic apparatus (the phragmoplast) develops centrifugally within the phragmosome. There has been considerable speculation on the nature of the elements that guide the phragmoplast to the cortical site previously occupied by the preprophase band of microtubules. This study demonstrates that F-actin bridges the leading margin of the outgrowing phragmoplast to the opposing cortex. Radial actin strands therefore provide a ‘memory’ of the predetermined division plane whose perimeter had been marked at preprophase by a band composed of microtubules and F-actin.

This relationship was perturbed with the herbicide, chloroisopropylphenyl carbamate. Preprophase bands of actin appear to form normally in herbicidetreated cells. However, cytokinesis does not occur within this predicted plane since the drug perturbs the mitotic spindle, forming three nuclei which become separated by Y-shaped, actin-containing phragmoplasts. Cytoplasmic actin strands connect the edges of the phragmoplast to the cortex. It is suggested that the irregular distribution of F-actin, which radiates from the herbicide-altered mitotic apparatus, provides alternative paths for outgrowth of the abnormal phragmoplasts.

Caffeine is known to cause failure of cell plate formation. But apart from inducing cytoplasmic ‘starbursts’ of F-actin in interphase cells it does not appear to have any effect on F-actin-containing division structures.

It is concluded that the formation of a transvacuolar phragmosome, spindle alignment and the ‘correct’ outgrowth of a planar cytokinetic apparatus to the predetermined boundary of the division site all involve F-actin.
Concanavalin A receptor ‘tipping’ inTetrahymenaand its relationship to cell adhesion during conjugation
Authors: Wolfe Jason , Feng Sunlian
Published: April 2021

Shortly after mixing cells of complementary mating types of Tetrahymena, the cells develop the ability to pair, a process inhibited by ConA, and the region joining the cells becomes ringed with ConA receptors. This study examines the arrival of ConA receptors at the conjugation junction by looking at cells in the period between mixing and pairing. By brief incubations with F-ConA at intervals after mixing, it was ascertained that some cells had fluorescent tips as early as 15 min. A kinetic analysis revealed that ‘tipping’ occurs in a manner that appears to be related to subsequent cell pairing. Cytoskeletal frameworks (CFs) were isolated under conditions in which ConA receptors remain attached. Western blot analysis of these structures revealed four major and several minor ConA-binding proteins. However, between mixing and the establishment of over 80 % paired cells, changes occurring in the banding pattern were slight. This indicates that new populations of ConA receptors are not produced to any great extent after mixing. Head-on examination of CFs showed that it was possible to monitor simultaneously the process of tip transformation (widening of the nonciliated area of the tip) and ConA-receptor localization. ConA receptors originate posterior to the tip, begin to occupy the surface of the tip in clusters as the tip widens and eventually coat the transformed tip. Finally, as cells join pairs, the receptors relocate to a ring around the conjugation junction. These data suggest that ConA receptors accumulate at the anterior tips and then concentrate at the edge of the junction. This could provide a mechanism for controlling cell-cell adhesion.