bluuebunny/crossref_metadata_2025_split huggingface dataset:
ZIP10 drives osteosarcoma proliferation and chemoresistance through ITGA10-mediated activation of the PI3K/AKT pathway
Authors: Li Hongyu , Shen Xin , Ma Mengjun , Liu Wenzhou , Yang Wen , Wang Peng , Cai Zhaopeng , Mi Rujia , Lu Yixuan , Zhuang Jiahao , Jiang Yuhang , Song Yihui , Wu Yanfeng , Shen Huiyong 
Published: October 2021

AbstractBackgroundThe zinc transporters Zrt- and Irt-related protein (ZIP/SLC39) are overexpressed in human tumors and correlate with poor prognosis; however, their contributions to carcinogenesis and chemoresistance in osteosarcoma (OS) remain unclear.MethodsWe collected 64 OS patient tissues with (n = 12) or without (n = 52) chemotherapy. The expression levels of ZIP10 were measured by immunohistochemistry and applied to prognostic analysis. ZIP10 was knocked down or overexpressed in OS cell lines to explore its effect on proliferation and chemoresistance. RNA sequencing, quantitative real-time PCR, and western blotting analysis were performed to explore ZIP10-regulated downstream target genes. A xenograft mouse model was established to evaluate the mechanisms by which ZIP10 modulates chemoresistance in OS cells.ResultsThe expression of ZIP10 was significantly induced by chemotherapy and highly associated with the clinical outcomes of OS. Knockdown of ZIP10 suppressed OS cell proliferation and chemoresistance. In addition, ZIP10 promoted Zn content-induced cAMP-response element binding protein (CREB) phosphorylation and activation, which are required for integrin α10 (ITGA10) transcription and ITGA10-mediated PI3K/AKT pathway activation. Importantly, ITGA10 stimulated PI3K/AKT signaling but not the classical FAK or SRC pathway. Moreover, overexpression of ZIP10 promoted ITGA10 expression and conferred chemoresistance. Treatment with the CREB inhibitor 666–15 or the PI3K/AKT inhibitor GSK690693 impaired tumor chemoresistance in ZIP10-overexpressing cells. Finally, a xenograft mouse model established by subcutaneous injection of 143B cells confirmed that ZIP10 mediates chemotherapy resistance in OS cells via the ZIP10-ITGA10-PI3K/AKT axis.ConclusionsWe demonstrate that ZIP10 drives OS proliferation and chemoresistance through ITGA10-mediated activation of the PI3K/AKT pathway, which might serve as a target for OS treatment.
Clinical foot measurements as a proxy for plantar pressure testing in people with diabetes
Authors: Chuter Vivienne H. , Spink Martin J. , David Michael , Lanting Sean , Searle Angela 
Published: October 2021

AbstractBackgroundHigh plantar pressures are associated with increased foot ulcer risk in people with diabetes. Identification of high plantar pressures in people with diabetes is clinically challenging due to time and cost constraints of plantar pressure testing. Factors affecting foot biomechanics, including reduced joint range of motion and foot deformity, are implicated in the development of high plantar pressures and may provide a method to clinically identify those at risk of pressure related complications. The aim of this study was to investigate the contribution of joint range of motion and foot deformity measures on plantar pressures in a community dwelling group with diabetes.MethodsBarefoot (Tekscan HR Mat™) and in‐shoe (Novel Pedar‐X®) plantar pressure variables, weight bearing ankle dorsiflexion, hallux range of motion, lesser toe deformities and hallux abductus (HAV) scale were assessed in 136 adults with diabetes (52.2% male; mean age 68.4 years). Multivariate multiple linear regression was used to assess the effect of the four biomechanical factors plus neuropathy and body mass index on plantar pressure variables. Non‐parametric bootstrapping was employed to determine the difference in plantar pressure variables for participants with two or more foot biomechanical pathologies compared to those with less than two pathologies.ResultsAlmost one third (32%) of the cohort had two or more foot biomechanical pathologies. Participants with two or more foot biomechanical pathologies displayed significant increases in all barefoot plantar pressure regions (except forefoot), compared to those with less than two pathologies. No significant changes were found for the in‐shoe plantar pressure variables. The regression model explains between 9.9% (95%CI: 8.4 to 11.4%) and 29.6% (95% CI: 28.2 to 31%), and between 2.5% (1.0 to 4.0%) and 43.8% (95% CI: 42.5–44.9%), of the variance in the barefoot and in‐shoe plantar pressure variables respectively.ConclusionsParticipants presenting with two or more factors affecting foot biomechanics displayed higher peak pressures and pressure time integrals in all foot regions compared to those with less than two factors. The tests used in this study could help clinicians detect elevated plantar pressures in people with diabetes and present an opportunity for early preventative interventions.
phasebook: haplotype-aware de novo assembly of diploid genomes from long reads
Authors: Luo Xiao , Kang Xiongbin , Schönhuth Alexander 
Published: October 2021

AbstractHaplotype-aware diploid genome assembly is crucial in genomics, precision medicine, and many other disciplines. Long-read sequencing technologies have greatly improved genome assembly. However, current long-read assemblers are either reference based, so introduce biases, or fail to capture the haplotype diversity of diploid genomes. We present phasebook, a de novo approach for reconstructing the haplotypes of diploid genomes from long reads. phasebook outperforms other approaches in terms of haplotype coverage by large margins, in addition to achieving competitive performance in terms of assembly errors and assembly contiguity.
Argus II retinal prosthesis for retinitis pigmentosa in the Middle East: The 2015 Pan-American Association of Ophthalmology Gradle Lecture
Authors: Arevalo J. Fernando , Al Rashaed Saba , Alhamad Tariq A. , Al Kahtani Eman , Al-Dhibi Hassan A. ,   for the KKESH Collaborative Retina Study Group, Mura Marco , Al Kahtani Eman , Nowilaty Sawsan , Al Rashaed Saba , Al-Dhibi Hassan A. , Al-Zahrani Yahya A. , Kozak Igor , Al-Sulaiman Sulaiman , Al-Abdullah Abdulelah , Al-Bar Ahmad , Al Dhafiri Yousef , Al Qahtani Abdullah , Al Rubaie Khalid , Al Shahrani Saeed , Al Shehri Maha , Al Ahmadi Badr , Al Hadlaq Abdulaziz , Al Harbi Majed , Al Oreany Abdulaziz , Fernando Arevalo J. 
Published: October 2021

Abstract
Background
To describe the outcomes of patients with retinitis pigmentosa (RP) who received the Argus II Retinal Prosthesis System.

Methods
This retrospective, interventional case series evaluated 10 consecutive patients who received the Argus II retinal implant and underwent visual function tests with the system on and system off. The main outcome measures were safety (the number, seriousness, and relatedness of adverse events), and visual function measured by computer-based objective tests, including square localization (SL) and direction of motion (DOM). Secondary measures included functional vision performance, including orientation and mobility (O&M) tasks.

Results
There were no intraoperative complications and all prostheses remained implanted at the end of follow up. The mean patient age was 41.3 years; mean duration of the implant in vivo was 2.1 years. One patient had a suture exposure over the coil suture tab and over the inferior case suture tab at 2 years postoperatively, which was managed successfully. One patient developed mild vitreous hemorrhage that resolved spontaneously. One patient developed high intraocular pressure postoperatively due to a tight scleral band (SB) that was managed successfully. Patients performed significantly better with the Argus II system on than off on all tasks.

Conclusion
Patients who received the Argus II had a safety profile out to 4 years post-implantation that was markedly better than that observed in the pre-approval phase of the Argus II. In this population of RP patients, the Argus II retinal prosthesis provided useful visual function over several years that likely translates into improved quality of life.
Trial Registration: clinicaltrials.gov identifier, NCT00407602.
Association Between Genetic Testing for Hereditary Breast Cancer and Contralateral Prophylactic Mastectomy Among Multiethnic Women Diagnosed With Early-Stage Breast Cancer
Authors: Ro Vicky , McGuinness Julia E. , Guo Boya , Trivedi Meghna S. , Jones Tarsha , Chung Wendy K. , Rao Roshni , Levinson Elana , Koval Carrie , Russo Donna , Chilton Ilana , Kukafka Rita , Crew Katherine D. 
Published: October 2021

PURPOSE: Increasing usage of multigene panel testing has identified more patients with pathogenic or likely pathogenic (P or LP) variants in low-moderate penetrance genes or variants of uncertain significance (VUS). Our study evaluates the association between genetic test results and contralateral prophylactic mastectomy (CPM) among patients with breast cancer. METHODS: We conducted a retrospective cohort study among women diagnosed with unilateral stage 0-III breast cancer between 2013 and 2020 who underwent genetic testing. We examined whether genetic test results were associated with CPM using multivariable logistic regression models. RESULTS: Among 707 racially or ethnically diverse women, most had benign or likely benign (B or LB) variants, whereas 12.5% had P or LP and 17.9% had VUS. Racial or ethnic minorities were twice as likely to receive VUS. Patients with P or LP variants had higher CPM rates than VUS or B or LB (64.8% v 25.8% v 25.9%), and highest among women with P or LP variants in high-penetrance genes (74.6%). On multivariable analysis, P or LP compared with B or LB variants were significantly associated with CPM (odds ratio = 4.24; 95% CI, 2.48 to 7.26). CONCLUSION: Women with P or LP variants on genetic testing were over four times more likely to undergo CPM than B or LB. Those with VUS had similar CPM rates as B or LB. Our findings suggest appropriate genetic counseling and communication of cancer risk to multiethnic breast cancer survivors.
Validation of a spatial agent-based model for Taenia solium transmission (“CystiAgent”) against a large prospective trial of control strategies in northern Peru
Authors: Pray Ian W. , Pizzitutti Francesco , Bonnet Gabrielle , Gonzales-Gustavson Eloy , Wakeland Wayne , Pan William K. , Lambert William E. , Gonzalez Armando E. , Garcia Hector H. , O’Neal Seth E. ,   for the Cysticercosis Working Group in Peru.
Published: October 2021

Background
The pork tapeworm (Taenia solium) is a parasitic helminth that imposes a major health and economic burden on poor rural populations around the world. As recognized by the World Health Organization, a key barrier for achieving control of T. solium is the lack of an accurate and validated simulation model with which to study transmission and evaluate available control and elimination strategies. CystiAgent is a spatially-explicit agent based model for T. solium that is unique among T. solium models in its ability to represent key spatial and environmental features of transmission and simulate spatially targeted interventions, such as ring strategy.

Methods/Principal findings
We validated CystiAgent against results from the Ring Strategy Trial (RST)–a large cluster-randomized trial conducted in northern Peru that evaluated six unique interventions for T. solium control in 23 villages. For the validation, each intervention strategy was replicated in CystiAgent, and the simulated prevalences of human taeniasis, porcine cysticercosis, and porcine seroincidence were compared against prevalence estimates from the trial. Results showed that CystiAgent produced declines in transmission in response to each of the six intervention strategies, but overestimated the effect of interventions in the majority of villages; simulated prevalences for human taenasis and porcine cysticercosis at the end of the trial were a median of 0.53 and 5.0 percentages points less than prevalence observed at the end of the trial, respectively.

Conclusions/Significance
The validation of CystiAgent represented an important step towards developing an accurate and reliable T. solium transmission model that can be deployed to fill critical gaps in our understanding of T. solium transmission and control. To improve model accuracy, future versions would benefit from improved data on pig immunity and resistance, field effectiveness of anti-helminthic treatment, and factors driving spatial clustering of T. solium infections including dispersion and contact with T. solium eggs in the environment.
Schistosomiasis messaging in endemic communities: Lessons and implications for interventions from rural Uganda, a rapid ethnographic assessment study
Authors: Ssali Agnes , Pickering Lucy , Nalwadda Edith , Mujumbusi Lazaaro , Seeley Janet , Lamberton Poppy H. L. 
Published: October 2021

Background
Over 240 million people are infected with schistosomiasis, the majority in sub-Saharan Africa. In Uganda, high infection rates exist in communities on the shores of Lake Victoria. Praziquantel mass drug administration (MDA) delivered by village health teams is the mainstay of schistosomiasis control. However, treatment uptake remains suboptimal, with many people unaware of treatment or thinking it is only for children. Furthermore, people are often rapidly reinfected post-treatment due to continued exposure. In three Schistosoma mansoni high endemicity lake-shore communities in Mayuge district, Eastern Uganda, we investigated the sources of schistosomiasis information, remembered content of information, and the perception of information and related practices towards the control of schistosomiasis.

Methods and principal findings
Data were collected from September 2017 to March 2018 using a rapid ethnographic assessment that included transect walks, observations, individual in-depth interviews and focus group discussions. Data were analysed thematically using iterative categorisation. We found that the main sources of schistosomiasis information included health workers at government facilities, village health teams, teachers, and radio programmes produced by the Ministry of Health. These messages described the symptoms of schistosomiasis, but did not mention the side effects of praziquantel treatment. Despite this messaging, the main cause of the disease and transmission was unclear to most participants. The translation of schistosomiasis on the radio into the local language ‘ekidada’—meaning swollen stomach—increased, rather than reduced, confusion about the cause(s) of schistosomiasis, due to believed links between ekidada and witchcraft, and prompted a reluctance to engage with treatment or preventative efforts.

Conclusion and significance
This study highlights gaps in schistosomiasis messaging. We recommend MDA is complemented by effective, evidence-based messaging on schistosomiasis transmission, prevention, and treatment, that is sensitive to local language and context issues, resulting in clear, concise, and consistent messages, to increase effectiveness.
Data quality assessment and associated factors in the health management information system among health centers of Southern Ethiopia
Authors: Solomon Mastewal , Addise Mesfin , Tassew Berhan , Balcha Bahailu , Abebe Amene 
Published: October 2021

Background
A well designed Health management information system is necessary for improving health service effectiveness and efficiency. It also helps to produce quality information and conduct evidence based monitoring, adjusting policy implementation and resource use. However, evidences show that data quality is poor and is not utilized for program decisions in Ethiopia especially at lower levels of the health care and it remains as a major challenge.

Method
Facility based cross sectional study design was employed. A total of 18 health centers and 302 health professionals were selected by simple random sampling using lottery method from each selected health center. Data was collected by health professionals who were experienced and had training on HMIS tasks after the tools were pretested. Data quality was assessed using accuracy, completeness and timeliness dimensions. Seven indicators from national priority area were selected to assess data accuracy and monthly reports were used to assess completeness and timeliness. Statistical software SPSS version 20 for descriptive statistics and binary logistic regression was used for quantitative data analysis to identify candidate variable.

Result
A total of 291 respondents were participated in the study with response rate of 96%. Overall average data quality was 82.5%. Accuracy, completeness and timeliness dimensions were 76%, 83.3 and 88.4 respectively which was lower than the national target. About 52.2% respondents were trained on HMIS, 62.5% had supervisory visits as per standard and only 55.3% got written feedback. Only 11% of facilities assigned health information technicians. Level of confidence [AOR = 1.75, 95% CI (0.99, 3.11)], filling registration or tally completely [AOR = 3.4, 95% CI (1.3, 8.7)], data quality check, supervision AOR = 1.7 95% CI (0.92, 2.63) and training [AOR = 1.89 95% CI (1.03, 3.45)] were significantly associated with data quality.

Conclusion
This study found that the overall data quality was lower than the national target. Over reporting of all indicators were observed in all facilities. It needs major improvement on supervision quality, training status to increase confidence of individuals to do HMIS activities.
Is physician implicit bias associated with differences in care by patient race for metastatic cancer-related pain?
Authors: Fiscella Kevin , Epstein Ronald M. , Griggs Jennifer J. , Marshall Mary M. , Shields Cleveland G. 
Published: October 2021

Rationale
Implicit racial bias affects many human interactions including patient-physician encounters. Its impact, however, varies between studies. We assessed the effects of physician implicit, racial bias on their management of cancer-related pain using a randomized field experiment.

Methods
We conducted an analysis of a randomized field experiment between 2012 and 2016 with 96 primary care physicians and oncologists using unannounced, Black and White standardized patients (SPs)who reported uncontrolled bone pain from metastatic lung cancer. We assessed implicit bias using a pain-adaptation of the race Implicit Association Test. We assessed clinical care by reviewing medical records and prescriptions, and we assessed communication from coded transcripts and covert audiotapes of the unannounced standardized patient office visits. We assessed effects of interactions of physicians’ implicit bias and SP race with clinical care and communication outcomes. We conducted a slopes analysis to examine the nature of significant interactions.

Results
As hypothesized, physicians with greater implicit bias provided lower quality care to Black SPs, including fewer renewals for an indicated opioid prescription and less patient-centered pain communication, but similar routine pain assessment. In contrast to our other hypotheses, physician implicit bias did not interact with SP race for prognostic communication or verbal dominance. Analysis of the slopes for the cross-over interactions showed that greater physician bias was manifested by more frequent opioid prescribing and greater discussion of pain for White SPs and slightly less frequent prescribing and pain talk for Black SPs with the opposite effect among physicians with lower implicit bias. Findings are limited by use of an unvalidated, pain-adapted IAT.

Conclusion
Using SP methodology, physicians’ implicit bias was associated with clinically meaningful, racial differences in management of uncontrolled pain related to metastatic lung cancer. There is favorable treatment of White or Black SPs, depending on the level of implicit bias.
Expression analysis of p16 and TOP2A protein biomarkers in cervical cancer lesions and their correlation with clinico-histopathological characteristics in a referral hospital, Tanzania
Authors: Zuberi Zavuga , Mremi Alex , Chilongola Jaffu O. , Semango George , Sauli Elingarami 
Published: October 2021

Introduction
Biomarkers yield important information for early diagnosis of cervical cancer. However, they are rarely applied for prognosis of cervical cancer in Tanzania, where visual inspection assay with acetic acid or Lugol’s iodine and Pap test are being used as the standard screening/ diagnostic methods.

Methods
This was a retrospective hospital-based cross-sectional study that was conducted to assess cyclin-dependent kinase inhibitor (p16) and topoisomerase II-alpha (TOP2A) proteins expression among women seeking cervical cancer care at Kilimanjaro Christian Medical Centre, Tanzania between May 1, 2017 and May 10, 2018. Immunohistochemistry technique was used to detect the expressions of p16 and TOP2A proteins from the retrieved formalin-fixed and paraffin-embedded (FFPE) cervical biopsies.

Results
A total of 145 patients, with a mean age of 52.1 ± 12.9 years, were included in this study. Upon immunohistochemistry staining, 103 (71.0%) and 90 (62.1%) were p16 and TOP2A positive respectively. There was a strong association between histopathological class and p16/TOP2A expression levels (Fisher’s exact test, p<0.001). Moreover, there was a strong positive correlation between p16/TOP2A and cancerous cervical lesions (Spearman’s rank correlation coefficients = 0.833 and 0.687, p = 0.006 and 0.005, respectively). The age-adjusted odds ratio for predicting cervical cancer lesions were independently significant for p16/TOP2A biomarkers in FFPE cervical tissues [p16: OR = 1.142 (95% CI: 1.059–1.232, p<0.001) and TOP2A: OR = 1.046 (95% CI: 1.008–1.085, p = 0.015)]. Importantly, the diagnostic performance of p16 was higher than that of TOP2A in the diagnosis of cancerous lesions from non-cancerous cervical lesions (sensitivity: 97.2% versus 77.6%, accuracy: 92.8% versus 87.8%, respectively).

Conclusion
Our study has highlighted that over-expression of TOP2A is related to the grade of cervical intraepithelial neoplasia but does not predict prognosis in cervical cancer. Similarly, expression of p16 is related to degree of histological dysplasia and malignancy, suggesting its prognostic and predictive value in the management of cervical cancers. Further bigger studies are needed to validate their applications in the early diagnosis of cervical cancer.