bluuebunny/crossref_metadata_2025_split huggingface dataset:
Public health genomics capacity assessment: readiness for large-scale pathogen genomic surveillance in Canada’s public health laboratories
Authors: Nadon C. , Croxen M. , Knox N. , Tanner J. , Zetner A. , Yoshida C. , Van Domselaar G. 
Published: September 2022

Abstract
Background
Along with rapid diagnostic testing, contact tracing, and public health measures, an effective pandemic response incorporates genomics-based surveillance. Large-scale SARS-CoV-2 genome sequencing is a crucial component of the global response to COVID-19. Characterizing the state of genomics readiness among Canada’s public health laboratories was necessary to inform strategic planning and deployment of capacity-building resources in the early stages of the pandemic.

Methods
We used a qualitative study design and focus group discussions, encompassing both technical and leadership perspectives, to perform an in-depth evaluation of the state of pathogen genomics readiness in Canada.

Results
We found substantial diversity in the state of readiness for SARS-CoV-2 genomic surveillance across Canada. Despite this variability, we identified common barriers and needs in the areas of specimen access, data flow and sharing, computing infrastructure, and access to highly qualified bioinformatics personnel.

Conclusions
These findings enable the strategic prioritization and deployment of resources to increase Canada’s ability to perform effective public health genomic surveillance for COVID-19 and prepare for future emerging infectious diseases. They also provide a unique qualitative research model for use in capacity building.
Computer grading of lung disease severity in patients with lymphangioleiomyomatosis referred for transplantation
Authors: Taveira-DaSilva Angelo M. , Gopalakrishnan Vissaagan , Yao Jianhua , Chen Marcus Y. , Julien-Williams Patricia , Jones Amanda M. , Pacheco-Rodriguez Gustavo , Moss Joel 
Published: September 2022

Abstract
Objectives
Lymphangioleiomyomatosis (LAM) patients with severe lung disease may be considered for lung transplantation. Clinical, physiologic, and quality of life data are usually employed for referral. The aim of this study was to determine whether computed tomographic measurement of lung volume occupied by cysts (cyst score) complemented clinical and physiologic data in supporting referral for transplantation.

Methods
Forty-one patients were studied. Pre-referral clinical data, pulmonary function tests, exercise testing, and high-resolution computed tomography (HRCT) scans were obtained. From HRCT, a computer-aided diagnostic program was employed to calculate cyst scores. These data were compared to those of 41 age-matched LAM patients not referred for lung transplantation.

Results
Cyst score, and % predicted FEV1 and DLCO were respectively, 48.1 ± 9.4%, 36.5 ± 9.1%, and 35.0 ± 10.7%. For the control group, cyst score, FEV1, and DLCO were respectively, 14.8 ± 8.3%, 77.2 ± 20.3%, and 66.7 ± 19.3%. Cyst score values showed a normal distribution. However, the frequency distribution of FEV1 was skewed to the right while the distribution of DLCO was bimodal. Correlations between cyst score and FEV1 and DLCO for the study group were respectively, r = − 0.319 and r = − 0.421.

Conclusions
LAM patients referred for lung transplantation had nearly 50% of lungs occupied by cysts. Correlations between cyst score and FEV1 or DLCO were weak; as shown previously, DLCO was better related to cyst number while FEV1 had a better association with cyst size. Given its normal distribution, cyst score measurements may assist in evaluation of pre-transplant severity of lung disease before referral for transplantation.
Isolated adrenocorticotropic hormone deficiency associated with sintilimab therapy in a patient with advanced lung adenocarcinoma: a case report and literature review
Authors: Lin Si-Hong , Zhang Ao , Li Lu-Zhen , Zhao Liang-Chen , Wu Le-Xia , Fang Can-Tu 
Published: September 2022

Abstract
Background
Several immune checkpoint inhibitors have been implemented for cancer treatment which have shown some degree of antitumor effcacy, while immune-related adverse events (irAEs) that affect multiple organ functions ensue which obviously should not be neglected. Though less common than other kinds of irAEs, Immune checkpoint inhibitors (ICIs) related Isolated ACTH deficiency (IAD) may cause long-term damage to pituitary-adrenal axis. Several case reports are available about IAD during anti-PD-1 therapy. We report the first case of immune checkpoint inhibitor-induced IAD following 3 month of sintilimab therapy.

Case presentation
A 66-year-old Chinese man was diagnosed with stage IIIB lung adenocarcinoma with involving ipsilateral intrapulmonary and hilar lymph node metastasis. After 3 months of combination therapy of nedaplatin, pemetrexed and sintilimab, the patient presented with general fatigue, nausea and vomiting. Laboratory investigation at admission revealed hyponatremia and hypokalemia. Further investigation revealed adrenocorticotropic hormone and cortisol levels were far below than normal limits. His other pituitary hormone levels were normal, except for mild elevation of follicle stimulating hormone and estradiol. Cranic magnetic resonance imaging showed a normal pituitary gland. Isolated adrenocorticotropic hormone deficiency was diagnosed, and corticosteroid replacement therapy was administered, leading to a significant improvement of his symptoms while ACTH level maintaining low level.

Conclusions
Our patient developed isolated ACTH deficiency during combination cancer treatment with chemotherapy and sintilimab. Although isolated ACTH deficiency due to anti-PD-1 including sintilimab therapy is rare occurrence, it can often cause severe clinical symptoms. Its diagnosis basically relies on clinical symptoms and endocrinological examination. Unlike traditional hypophysitis diagnosed by cranial MRI, pituitary MRI of IAD due to anti-PD-1 often indicates normal pituitary gland implying that over-reliance on imaging findings is not recommended. Even if clinical symptoms have relieved after corticosteroid replacement therapy was commenced, low levels of ACTH or cortisol could maintain for a long period which highlights the need for long term corticosteroid therapy. The purpose of the current report was to provide increased awareness of early detection and therapy of IAD.
Qualitative evaluation of postdoctoral trainee and faculty advisor experiences within a research-intensive school of pharmacy
Authors: McLaughlin JE , Morbitzer KA , Hahn F , Minshew L , Brouwer KLR 
Published: September 2022

AbstractBackgroundPostdoctoral trainees play a vital role in securing grant funding, building alliances, and mentoring graduate students under the guidance of a mentor who can help develop their intellectual independence. However, the experiences of postdoctoral trainees, particularly within health professions schools, is largely unexplored. The purpose of this study was to investigate the experiences of postdoctoral trainees and faculty advisors at a public four-year school of pharmacy and identify areas of opportunity to improve postdoctoral training.MethodsFocus groups and interviews were conducted to elicit participants’ experiences, perceptions, and suggestions for improvement. Stakeholder groups included postdoctoral trainees and faculty who serve as postdoctoral advisors. Thematic coding was used to identify semantic themes, and summaries of participant perceptions were generated. Results were mapped to the identity-trajectory framework.ResultsParticipants described various experiences related to intellectual growth, networking opportunities, and institutional support. In addition, participant agency was critical for developing career goals and navigating transitions. COVID-19 introduced unique challenges associated with transitioning to remote work and managing goals/motivation. Areas of opportunity were identified, such as improving infrastructure, enhancing mentoring, and enhancing communication.ConclusionPostdoctoral trainees play a critical role in the success of academic institutions. Scholarly endeavors that explore postdoctoral experiences, specifically those utilizing qualitative methods, can help pharmacy education better understand and meet the needs of postdoctoral trainees and faculty advisors. This study provides insight into the experiences of postdoctoral scholars and provides evidence for improving these training programs in schools of pharmacy.
Potential of selected plant extracts to control severe subacute ruminal acidosis in vitro as compared with monensin
Authors: Ahmed Mariam G. , Al-Sagheer Adham A. , El-Zarkouny Samir Z. , Elwakeel Eman A. 
Published: September 2022

Abstract
Background
In recent years, researchers have become increasingly interested in developing natural feed additives that can stabilize ruminal pH and thus prevent or eliminate the risk of severe subacute rumen acidosis. Herein, 3 experiments were conducted using a semi-automated in vitro gas production technique. In the experiment (Exp.) 1, the efficacy of 9 plant extracts (1.5 mg/ml), compared to monensin (MON; 12 μg/ml), to counteract ruminal acidosis stimulated by adding glucose (0.1 g/ml) as a fermentable carbohydrate without buffer was assessed for 6 h. In Exp. 2, cinnamon extract (CIN) and MON were evaluated to combat glucose-induced acidosis with buffer use for 24 h. In Exp. 3, the effect of CIN and MON on preventing acidosis when corn or barley grains were used as substrate was examined.

Results
In Exp. 1, cinnamon, grape seeds, orange, pomegranate peels, propolis, and guava extracts significantly increased (P < 0.05) pH compared to control (CON). Both CIN and MON significantly increased the pH (P < 0.001) but reduced cumulated gas production (P < 0.01) compared to the other treatments. In Exp. 2, the addition of CIN extract increased (P < 0.01) pH value compared to CON at the first 6 h of incubation. However, no significant differences in pH values between CIN and CON at 24 h of incubation were observed. The addition of CIN extract and MON decreased (P < 0.001) lactic acid concentration and TVFA compared to CON at 24 h. The CIN significantly (P < 0.01) increased acetate: propionate ratio while MON reduced it. In Exp. 3, both CIN and MON significantly increased (P < 0.05) ruminal pH at 6 and 24 h and reduced lactic acid concentration at 24 h compared to CON with corn as substrate. However, CIN had no effect on pH with barley substrate at all incubation times.

Conclusions
It can be concluded that CIN can be used effectively as an alternative antibiotic to MON to control ruminal acidosis when corn is used as a basal diet.
Factors influencing health workers’ compliance with the WHO intermittent preventive treatment for malaria in pregnancy recommendations in the Northern Region, Ghana
Authors: Mohammed Abdul Gafaru , Duah Dwomoh , Kenu Ernest , Nonvignon Justice , Manu Alex , Bonful Harriet Affran 
Published: September 2022

Abstract
Background
Although IPTp-SP is a lifesaving World Health Organization (WHO) recommended preventive intervention for pregnant women in malaria-endemic regions, IPTp-SP uptake in the Northern region of Ghana is much lower than the sub-optimal national coverage level. Assessing the extent of health workers’ compliance and its associated factors will generate valuable pointers to be targeted at the program level. The study examined the factors influencing health workers’ compliance with the WHO recommended guidelines for IPTp-SP in the Northern Region.

Methods
A cross-sectional study among 315 health workers in the Northern region was conducted. Semi-structured questionnaires were used to collect data on health workers’ sociodemographic characteristics, facility-based factors and knowledge level. Data were collected on health workers’ compliance with the recommended practices through covert observations using a checklist. Facility observations were carried out using a checklist. Crude and adjusted logistic regression were used to determine predictors of health workers’ compliance, at a 5% significance level adjusting for clustering.

Results
Of the 315 health workers studied, the median age was 29 years (26–34 years). Females constituted (80.5%; 252) of the 313 workers. The majority (47.4%;148) of the 312 health workers were midwives. Overall, 56.2% (CI 51.0 – 62.0) were adequately complying with the recommended guidelines. Lower levels of compliance were recorded in health centres 15.6% (5.0 – 33.0) and CHPS compounds 21.2% (11.0 – 35.0). The factors associated with compliance included health workers’ knowledge (aOR = 7.64, 95% CI 4.21 – 13.87, p < 0.001), job satisfaction (aOR 10.87, 95% CI 7.04 – 16.79, p < 0.001), in-service training (aOR 10.11, 95% CI 4.53 – 22.56, p < 0.001), supervision (aOR 4.01, 95% CI 2.09 – 7.68, p < 0.001), availability of job aids (aOR 3.61, 95% CI 2.44 – 5.35, p < 0.001), health workers experience (aOR = 10.64, 95% CI 5.99 – 18.91, p < 0.001) and facility type (aOR 0.03, 95% CI 0.01–0.07, p < 0.001).

Conclusion
Compliance with the recommended IPTp-SP guidelines is suboptimal in the region, with lower-level health facilities recording the least compliance levels. Health centres and CHPS facilities should be prioritized in distributing limited resources to improve health worker quality of care for antenatal care clients.
Application of MOF-based nanotherapeutics in light-mediated cancer diagnosis and therapy
Authors: Zhao Dan , Zhang Wang , Yu Shuang , Xia Si-Lei , Liu Ya-Nan , Yang Guan-Jun 
Published: September 2022

AbstractLight-mediated nanotherapeutics have recently emerged as promising strategies to precisely control the activation of therapeutic reagents and imaging probe both in vitro and in vivo, largely ascribed to their unique properties, including minimally invasive capabilities and high spatiotemporal resolution. Nanoscale metal–organic frameworks (NMOFs), a new family of hybrid materials consisting of metal attachment sites and bridging ligands, have been explored as a new platform for enhanced cancer diagnosis and therapy due to their tunable size, modifiable surface, good biocompatibility, high agent loading and, most significantly, their ability to be preferentially deposited in tumors through enhanced permeability and retention (EPR). Especially the light-driven NMOF-based therapeutic platform, which not only allow for increased laser penetration depth and enhanced targeting, but also enable imaging-guided or combined treatments. This review provides up-to-date developments of NMOF-based therapeutic platforms for cancer treatment with emphasis on light-triggered therapeutic strategies and introduces their advances in cancer diagnosis and therapy in recent years.Graphic Abstract
Profiles of transcriptome and metabolic pathways after hypobaric hypoxia exposure
Authors: Xu Jin , Chen Wen-jie , Wang Zhan , Xin Ming-yuan , Gao Shen-han , Liu Wen-jing , Wang Kai-kun , Ma Jing-wei , Yan Xin-zong , Ren Yan-ming 
Published: September 2022

AbstractBackgroundHypoxia is a risk factor for non-alcoholic fatty liver diseases, leading to permanent imbalance of liver lipid homeostasis and steatohepatitis. However, a detailed understanding of the metabolic genes and pathways involved remains elusive.MethodsIn vivo experiments were designed to analyze body weight and lipid metabolism changes of rats under hypoxia. After this, we combined microarray analysis and gene overexpression experiments to validate the core mechanisms involved in the response to hypoxia.ResultsThe hypobaric hypoxia treated rats exhibited significantly increased serum triglycerides (TG) (p < 0.05), despite no significant changes in serum alanine aminotransferase (ALT) and blood glucose (BG) were observed. In addition, serum high-density lipoprotein cholesterol (HDL-C) greatly increased after 3 days and then returned to normal level at 30 days. Interestingly, serum low-density lipoprotein cholesterol (LDL-C) showed an opposite pattern. Transcriptome analysis, qRT-PCR, ICC revealed that the genes PPARA, ANGPTL4, CPT-I, ACC and LPL play a crucial role in response to hypobaric hypoxia. IPA pathway analysis further confirmed that PPARA-mediated regulation of ANGPTL4 participated in TG clearance and lipoprotein metabolism. Finally, the PPARA-ANGPTL4 pathway was validated in rats and HL 7702 cells treated with Fenofibrate, a PPARA specific agonist.ConclusionsOur study showed this pathway plays an important role on lipid metabolism caused by hypobaric hypoxia and the potential target genes associated with oxygen-dependent lipid homeostasis in the liver.
Surgical staging of apparent early-stage ovarian mucinous carcinoma
Authors: Yuan Zhen , Zhang Ying , Cao Dongyan , Shen Keng 
Published: September 2022

Abstract
Objectives
The aim of the study was to explore the rate of upstaging after complete surgical staging among patients with apparent FIGO stage I ovarian mucinous carcinoma.

Methods
Ovarian mucinous carcinoma patients with surgical treatment at the Peking Union Medical College Hospital between October 2020 and January 1994 were retrospectively reviewed.

Results
In total, 163 patients were included in this study. Surgical restaging was performed in 89 patients after initial incomplete surgical staging, and one-step complete surgical staging was performed in 74 patients. Among these initially incompletely staged patients, residual tumors were found in 16 patients (16/89, 17.9%). Among the 19 patients with apparent FIGO stage IA, no patient was found to have residual tumors after incomplete staging surgery, according to the final pathology result of restaging surgery. Ovarian cystectomy (OR=4.932, 95% CI= 1.347–18.058, P=0.016) was an independent risk factor for residual tumors after incomplete staging surgery. Among all 163 patients, upstaging occurred in 15 patients (15/163, 9.2%). Among 44 apparent FIGO stage IA patients, no patient was upstaged to FIGO II–IVB. Moreover, both a history of ovarian mucinous tumor (OR=4.745, 95% CI= 1.132–19.886, P=0.033) and bilateral ovary involvement (OR=9.739, 95% CI= 2.016–47.056, P=0.005) were independent risk factors for upstaging to FIGO stage II–IVB.

Conclusions
For patients with apparent FIGO stage IA disease, the possibility of residual tumors and upstaging is relatively low. For patients with cystectomy, bilateral mucinous carcinomas, or a history of ovarian mucinous tumors, complete staging surgery maintains greater significance.
Overexpression of PBK/TOPK relates to poor prognosis of patients with breast cancer: a retrospective analysis
Authors: Qiao Liang , Ba Jinling , Xie Jiping , Zhu Ruiping , Wan Yi , Zhang Min , Jin Zeyu , Guo Zicheng , Yu Jiaxuan , Chen Sijing , Yao Yongqiang 
Published: September 2022

Abstract
Background
PDZ-binding kinase/T-lymphokine-activated killer cell-derived protein kinase (PBK/TOPK) is a potential prognostic indicator for patients with breast cancer. The objective of the present study was to explore the relationship between PBK/TOPK expression and clinicopathological indicators as well as the survival of patients with breast cancer.

Methods
Immunohistochemical staining was used to detect the expression of PBK/TOPK in 202 cases of breast cancer tissues. The relationship between PBK/TOPK and clinicopathological parameters was evaluated using Spearman’s rank-order correlation. The difference in PBK/TOPK expression among different molecular types was analyzed with the chi-square test. Kaplan-Meier analysis was used to create a survival curve and the log rank test was used to analyze the overall survival (OS) and disease-free survival (DFS). Prognostic correlation was assessed using univariate and multivariate Cox regression analyses.

Results
Among 202 breast cancer samples, PBK/TOPK was expressed (“+” and “++”) in 182 samples (90.1%). In addition, the histological grade, TNM stages, lymph node metastasis, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 were positively associated with PBK/TOPK expression. With regard to the molecular type, the expression of PBK/TOPK is different. The expression level of PBK/TOPK was negatively correlated with both the OS and DFS of breast cancer patients. The difference in the above results is meaningful (P < 0.05).

Conclusions
PBK/TOPK is overexpressed in breast cancer, and the expression is closely related to the clinicopathological characteristics of the disease. Breast cancer patients with high expression of PBK/TOPK have a poor prognosis. Therefore, healthcare providers can optimize breast cancer management using this indicator.
Response to comment on “Pooled analysis of Xpert bladder cancer based on the 5 mRNAs for rapid diagnosis of bladder carcinoma”
Authors: Xie Yu-Fei , Liu Ye-Ling , Guo Xu-Guang 
Published: September 2022

AbstractThis article is a response to “comment on ‘Pooled analysis of Xpert bladder cancer based on the 5 mRNAs for rapid diagnosis of bladder carcinoma’” by Gopal Sharma. With this comment, author highlighted the strengths and limitations of the study. With this response, we respond to this and make a comparison of the results and conclusions.
Development and validation of a pre- and intra-operative scoring system that distinguishes between non-advanced and advanced axillary lymph node metastasis in breast cancer with positive sentinel lymph nodes: a retrospective study
Authors: Murata Takeshi , Watase Chikashi , Shiino Sho , Kurita Arisa , Ogawa Ayumi , Jimbo Kenjiro , Iwamoto Eriko , Yoshida Masayuki , Takayama Shin , Suto Akihiko 
Published: September 2022

Abstract
Background
There are currently no scoring-type predictive models using only easily available pre- and intraoperative data developed for assessment of the risk of advanced axillary lymph node metastasis (ALNM) in patients with breast cancer with metastatic sentinel lymph nodes (SLNs). We aimed to develop and validate a scoring system using only pre- and intraoperative data to distinguish between non-advanced (≤ 3 lymph nodes) and advanced (> 3 lymph nodes) ALNM in patients with breast cancer with metastatic SLNs.

Methods
We retrospectively identified 804 patients with breast cancer (cT1-3cN0) who had metastatic SLNs and had undergone axillary lymph node dissection (ALND). We evaluated the risk factors for advanced ALNM using logistic regression analysis and developed and validated a scoring system for the prediction of ALNM using training (n = 501) and validation (n = 303) cohorts, respectively. The predictive performance was assessed using the receiver operating characteristic (ROC) curve, area under the curve (AUC), and calibration plots.

Results
Ultrasound findings of multiple suspicious lymph nodes, SLN macrometastasis, the ratio of metastatic SLNs to the total number of SLNs removed, and the number of metastatic SLNs were significant risk factors for advanced ALNM. Clinical tumor size and invasive lobular carcinoma were of borderline significance. The scoring system based on these six variables yielded high AUCs (0.90 [training] and 0.89 [validation]). The calibration plots of frequency compared to the predicted probability showed slopes of 1.00 (training) and 0.85 (validation), with goodness-of-fit for the model. When the cutoff score was set at 4, the negative predictive values (NPVs) of excluding patients with advanced ALNM were 96.8% (training) and 96.9% (validation). The AUC for predicting advanced ALNM using our scoring system was significantly higher than that predicted by a single independent predictor, such as the number of positive SLNs or the proportion of positive SLNs. Similarly, our scoring system also showed good discrimination and calibration ability when the analysis was restricted to patients with one or two SLN metastases.

Conclusion
Our easy-to-use scoring system can exclude advanced ALNM with high NPVs. It may contribute to reducing the risk of undertreatment with adjuvant therapies in patients with metastatic SLNs, even if ALND is omitted.