bluuebunny/crossref_metadata_2025_split huggingface dataset:
PIONEER-Panc: a platform trial for phase II randomized investigations of new and emerging therapies for localized pancreatic cancer
Authors: Douglas Julia E. , Liu Suyu , Ma Junsheng , Wolff Robert A. , Pant Shubham , Maitra Anirban , Tamm Eric P. , Bhosale Priya , Katz Matthew H. G. , Varadhachary Gauri R. , Koay Eugene J. 
Published: January 2022

Abstract
Background
Personalized and effective treatments for pancreatic ductal adenocarcinoma (PDAC) continue to remain elusive. Novel clinical trial designs that enable continual and rapid evaluation of novel therapeutics are needed. Here, we describe a platform clinical trial to address this unmet need.

Methods
This is a phase II study using a Bayesian platform design to evaluate multiple experimental arms against a control arm in patients with PDAC. We first separate patients into three clinical stage groups of localized PDAC (resectable, borderline resectable, and locally advanced disease), and further divide each stage group based on treatment history (treatment naïve or previously treated). The clinical stage and treatment history therefore define 6 different cohorts, and each cohort has one control arm but may have one or more experimental arms running simultaneously. Within each cohort, adaptive randomization rules are applied and patients will be randomized to either an experimental arm or the control arm accordingly. The experimental arm(s) of each cohort are only compared to the applicable cohort specific control arm. Experimental arms may be added independently to one or more cohorts during the study. Multiple correlative studies for tissue, blood, and imaging are also incorporated.

Discussion
To date, PDAC has been treated as a single disease, despite knowledge that there is substantial heterogeneity in disease presentation and biology. It is recognized that the current approach of single arm phase II trials and traditional phase III randomized studies are not well-suited for more personalized treatment strategies in PDAC. The PIONEER Panc platform clinical trial is designed to overcome these challenges and help advance our treatment strategies for this deadly disease.

Trial registration
This study is approved by the Institutional Review Board (IRB) of MD Anderson Cancer Center, IRB-approved protocol 2020-0075. The PIONEER trial is registered at the US National Institutes of Health (ClinicalTrials.gov) NCT04481204.
The impact of young age (< 40 years) on the outcome of a cohort of patients with primary non-metastatic breast cancer: analysis of 10-year survival of a prospective study
Authors: Bouferraa Youssef , Haibe Yolla , Chedid Andrea , Jabra Elio , Charafeddine Maya , Temraz Sally , Mukherji Deborah , El Saghir Nagi , Shamseddine Ali 
Published: January 2022

Abstract
Background
The role of young age (< 40 years) at diagnosis as an independent risk factor for adverse outcomes in female patients with breast cancer has been highlighted in several studies. In this prospective study, we assessed the difference in 10-year survival between two groups of patients diagnosed with non-metastatic breast cancer based on an age cutoff of 40 years. We also assessed the impact of factors including tumor characteristics, molecular markers and immunohistochemical markers on survival outcomes, highlighting the interaction of those variables with age.

Methods
A total of 119 female patients with newly diagnosed non-metastatic breast cancer were recruited at the American University of Beirut Medical Center (AUBMC) between July 2011 and May 2014. Patients were recruited and divided into 2 age groups (< 40 and ≥ 40 years). In addition to clinical characteristics, we assessed immunohistochemistry including estrogen, progesterone and HER2 receptors, p53, cyclin B1, vascular endothelial growth factor receptor (VEGFR), and ki-67. Germline BRCA mutations were also performed on peripheral blood samples. Patient and tumor characteristics were compared between the age groups. 10-year overall survival (OS) and disease-free survival (DFS) were estimated accordingly. Cox regression analysis was performed in order to assess the effect of the different variables on clinical outcomes.

Results
After a median Follow-up of 96 (13–122) months, the estimated 10-year OS was 98.6% for patients ≥40 as compared to 77.6% in patients < 40 (p = 0.001). A similar trend was found for 10-year DFS reaching 90% for patients ≥40 and 70.4% for those < 40 (p = 0.004). On multivariate analysis for DFS and OS, only younger age (< 40 years), higher stage and triple negative phenotype among other parameters assessed significantly affected the outcome in this cohort.

Conclusion
This prospective study confirms the association between younger age and adverse survival outcomes in patients with non-metastatic breast cancer. Future studies of the whole genome sequences may reveal the genomic basis underlying the clinical differences we have observed.
Prospective study evaluating dynamic changes of cell-free HPV DNA in locoregional viral-associated oropharyngeal cancer treated with induction chemotherapy and response-adaptive treatment
Authors: Rosenberg Ari J. , Izumchenko Evgeny , Pearson Alexander , Gooi Zhen , Blair Elizabeth , Karrison Theodore , Juloori Aditya , Ginat Daniel , Cipriani Nicole , Lingen Mark , Sloane Hillary , Edelstein Daniel L. , Keyser Kirsten , Fredebohm Johannes , Holtrup Frank , Jones Frederick S. , Haraf Daniel , Agrawal Nishant , Vokes Everett E. 
Published: January 2022

Abstract
Background
Human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) has a favorable prognosis which has led to efforts to de-intensify treatment. Response-adaptive de-escalated treatment is promising, however improved biomarkers are needed. Quantitative cell-free HPV-DNA (cfHPV-DNA) in plasma represents an attractive non-invasive biomarker for grading treatment response and post-treatment surveillance. This prospective study evaluates dynamic changes in cfHPV-DNA during induction therapy, definitive (chemo)radiotherapy, and post-treatment surveillance in the context of risk and response-adaptive treatment for HPV + OPC.

Methods
Patients with locoregional HPV + OPC are stratified into two cohorts: High risk (HR) (T4, N3, $$\ge$$
≥
20 pack-year smoking history (PYH), or non-HPV16 subtype); Low risk (LR) (all other patients). All patients receive induction chemotherapy with three cycles of carboplatin and paclitaxel. LR with ≥ 50% response receive treatment on the single-modality arm (minimally-invasive surgery or radiation alone to 50 Gy). HR with ≥ 50% response or LR with ≥ 30% and < 50% response receive treatment on the intermediate de-escalation arm (chemoradiation to 50 Gy with cisplatin). All other patients receive treatment on the regular dose arm with chemoradiation to 70 Gy with concurrent cisplatin. Plasma cfHPV-DNA is assessed during induction, (chemo)radiation, and post-treatment surveillance. The primary endpoint is correlation of quantitative cfHPV-DNA with radiographic response.

Discussion
A de-escalation treatment paradigm that reduces toxicity without compromising survival outcomes is urgently needed for HPV + OPC. Response to induction chemotherapy is predictive and prognostic and can select candidates for de-escalated definitive therapy. Assessment of quantitative cfHPV-DNA in the context of response-adaptive treatment of represents a promising reliable and convenient biomarker-driven strategy to guide personalized treatment in HPV + OPC.

Trial registration
This trial is registered with ClinicalTrials.gov on October 1st, 2020 with Identifier: NCT04572100.
Integration of breast cancer care in a middle-income country: learning from Suandok Breast Cancer Network (SBCN)
Authors: Chitapanarux Imjai , Onchan Wimrak , Wongmaneerung Panchaporn , Somwangprasert Areewan , Bunyoo Nongnuch , Ditsatham Chagkrit , Watcharachan Kirati , Charoentum Chaiyut , Sripan Patumrat , Chumachote Ausreeya , Maneesai Puttachart 
Published: January 2022

Abstract
Background
Breast cancer incidence in Northern Thailand has shown a continuous increase since records began in 1983. In 2002 the urgency of the situation prompted Maharaj Nakorn Chiang Mai Hospital to initiate the Suandok Breast Cancer Network (SBCN).

Methods
The SBCN is a not-for-profit organization in the university hospital which serves as a training and education center and provides highly specialized medical care for patients in Chiang Mai and in 5 provinces of northern Thailand, with the key mission of improving breast cancer care. The short-term goal was to overcome the barriers to engagement with breast cancer and its treatment and the long-term goal was to increase the overall survival rate of breast cancer patients in our region.

Results
We enrolled breast cancer patients treated at Maharaj Nakorn Chiang Mai Hospital between January 2006 and December 2015 and divided into 2 cohorts: 1485 patients who were diagnosed from 2006 to 2009 (cohort 1: early implementation of SBCN) and 2383 patients who were diagnosed from 2010 to 2015 (cohort 2: full implementation of SBCN). Criteria to measure improved cancer waiting time (CWT) would include: time to diagnosis, time to surgery, and time to radiotherapy. The 5-year overall survival (OS) of the cohort 2 was higher than that in cohort 1, at 73.8 (72.0–75.5) compared to 71.5 (69.2–73.7) (p-value = 0.03).

Conclusions
Reasons behind the success of project include the uniformity of care encouragement, service network development and timely access to each step of breast cancer management. The model used in SBCN could be adopted as a learning guide to improve healthcare access and outcome for breast cancer patients in low- to middle-income countries.
Using Belgian pharmacy dispensing data to assess antibiotic use for children in ambulatory care
Authors: Dillen Hannelore , Burvenich Ruben , De Burghgraeve Tine , Verbakel Jan Y. 
Published: January 2022

Abstract
Background
The desired effect of antibiotics is compromised by the rapid escalation of antimicrobial resistance. Children are particularly at high-risk for unnecessary antibiotic prescribing, which is owing to clinicians’ diagnostic uncertainty combined with parents’ concerns and expectations. Recent Belgian data on ambulatory antibiotic prescribing practices for children are currently lacking. Therefore, we aim to analyse different aspects of antibiotic prescriptions for children in ambulatory care.

Methods
Pharmacy dispensing data on antibiotics for systematic use referring from 2010 to 2019 were retrieved from Farmanet, a database of pharmaceutical dispensations in community pharmacies. Population data were obtained from the Belgian statistical office (Statbel). Descriptive statistics were performed in Microsoft Excel. The Mann-Kendall test for trend analysis and the seasplot function for seasonality testing were conducted in R.

Results
The past decade, paediatric antibiotic use and expenditures have relatively decreased in Belgian ambulatory care with 35.5% and 44.3%, respectively. The highest volumes of antibiotics for children are prescribed by GPs working in Walloon region and rural areas, to younger children, and during winter. The most prescribed class of antibiotics for children are the penicillins and the biggest relative reduction in number of packages is seen for the sulfonamides and trimethoprim and quinolone antibacterials.

Conclusions
Paediatric antibiotic use has decreased in Belgian ambulatory care. Further initiatives are needed to promote prudent antibiotic prescribing in ambulatory care.
Time to death among HIV-infected under-five children after initiation of anti-retroviral therapy and its predictors in Oromiya liyu zone, Amhara region, Ethiopia: a retrospective cohort study
Authors: Weldemariam Sintayehu Argaw , Dagnew Zewdu , Tafere Yilkal , Bereka Tefera Marie , Bitewa Yibelu Bazezew 
Published: January 2022

Abstract
Background
Human Immunodeficiency Virus (HIV) is infection which mainly attacks immune system of an individual. Its disease progress is rapid in children and if treatment is not initiated nearly half of infected children will die by the second year of infection. In Ethiopia, nearly twenty four percent of HIV related death is happen to under-five children; however studies done in this specific age group are limited are with poor evidence of predictors.

Objectives
To determine time to death and identify predictors of death in HIV infected under- five children on antiretroviral therapy in Amhara regional state, Oromia ‘liyu’ zone, Northeast Ethiopia, from 2014 to 2019.

Methods
Institution based retrospective follow up study was conducted in 376 under-five HIV- infected children on antiretroviral therapy from January 2014 to December 2019 in health institutions in Oromia Liyu Zone, Amhara region, Ethiopia. Multivariable Cox-proportional hazard regression model was used to identify independent predictors of mortality in HIV- infected under-five children on antiretroviral therapy.

Result
At the end of follow up, 304 (80.85%) of HIV-infected children were alive, 39 (10.95%) were lost to follow up, 12 (3.19%) were transferred out and 21 (5.59%) were reported dead due to HIV/AIDS. The cumulative survival probabilities of children after 3, 6, 12, 24 and 36 months were 0.99, 0.98, 0.97, 0.89 and 0.87 respectively. The overall mean time to death was 19.7 months (95%CI = 18.74–20.67) with incidence of 5.9 deaths per 100 child-months (95%CI: 3.89–9.09). Children with severe malnutrition at baseline (AHR = 4.9; 95 CI: 1.04, 23.50), advanced WHO clinical stage at enrolment (AHR = 3.9; CI: 1.37, 10.88), poor adherence to ART (AHR = 6.56; CI: 3.33, 10.14) and with no history of Isoniazide prophylaxis were significantly associated to higher mortality events (AHR = 3.6; CI: 1.24, 10.18).

Conclusion
Death of HIV-infected under-five children on ART is high within the first one year after enrolment. The risk of death increased if the child was malnourished at beginning of treatment, had poor ART adherence, with advanced WHO clinical stages and lack of Isoniazide prophylaxis during their age of infancy.
Significance of the ‘line sign’ in the diagnosis of congenital imperforate anus on prenatal ultrasound
Authors: Yin Chan , Tong Lili , Nie Dan , Fei Zhihui , Tan Xiaoqun , Ma Mingxiang 
Published: January 2022

AbstractBackgroundThe prenatal diagnosis of foetal imperforate anus is difficult. Most previous studies have been case reports. To provide useful information for diagnosing foetal imperforate anus, a retrospective review of diagnostic approaches was conducted. Ultrasonography was performed in 19 cases of foetal imperforate anus from 2016 to 2019 at our prenatal diagnostic centre. The prenatal sonographic features and outcomes of each case were collected and evaluated.ResultThe anal sphincter of a normal foetus shows the ‘target sign’ on cross-sectional observation. Of the 19 cases of imperforate anus, 16 cases were diagnosed by the ultrasound image feature called the ‘line sign’. 1 case with tail degeneration was low type imperforate anus with the irregular ‘target sign’ not a real ‘target sign’. There was two false-negative case, in which the ‘target sign’ was found, but irregular.ConclusionIn this study, we find that the anus of a foetus with imperforate anus presents a ‘line sign’ on sonographic observation. The absence of the ‘target sign’ and then the presence of the ‘line sign’ can assist in the diagnosis of imperforate anus. The ‘line sign’ can be used as a secondary assessment to determine the type of the malformation following non visualization of the ‘target sign’. The higher the position of the imperforate anus is, the more obvious the ‘line sign’. It is worth noting that the finding of the short ‘line sign’ and irregularr ‘target sign’ can not ignore the low type imperforate anus.
Liver transplantation in a child with liver cirrhosis caused by langerhans cell histiocytosis: a case report
Authors: Wang Qi , Jin Shuguang , Xiang Bo , Chen Jing 
Published: January 2022

Abstract
Background
Langerhans cell histiocytosis (LCH) is a rare condition that has a variety of clinical manifestations. But LCH in children localized only in the hepatobiliary system is unusual.
Case presentation.
Here we reported a rare case of a 2-year-old boy who was serendipitously found to have elevated liver enzymes while undergoing treatment of a perianal abscess. After a period of earlier conservative treatment in another hospital, the perianal abscess had resolved but the levels of liver enzymes were still rising slowly. The child was then referred to our institution for a definitive diagnosis. After laboratory tests, imaging and pathological examinations, a diagnosis of liver cirrhosis and sclerosing cholangitis was established, although the cause was unclear. Subsequently, living-donor liver transplantation was performed due to deterioration in liver function. Following successful liver transplantation, a diagnosis of LCH localized only within the hepatobiliary system was finally confirmed, based on additional pathological and imaging investigation. Additionally, the BRAF V600E mutation in this patient was also confirmed. The child has now recovered without evidence of LCH recurrence.

Conclusions
LCH localized only within the hepatobiliary system is unusual. The presence of unexplainable sclerosing cholangitis and liver cirrhosis in any child should raise the suspicion of LCH.
Poor sleep quality is negatively associated with low cognitive performance in general population independent of self-reported sleep disordered breathing
Authors: Wang Zhongrong , Heizhati Mulalibieke , Wang Lin , Li Mei , Yang Zhikang , Lin Mengyue , Abudereyimu Reyila , Hong Jing , Yang Wenbo , Yao Ling , Liu Shasha , Hu Junli , Li Nanfang 
Published: January 2022

Abstract
Background
Sleep disordered breathing (SDB) plays a significant role in both sleep quality and cognition and whether it has an impact on the relationship between above two factors remains to be clear. The study aimed to explore the association between sleep quality and cognitive performance in general population by considering influence of sleep disordered breathing (SDB).

Methods
In this cross-sectional study, we enrolled subjects aged ≥ 18 years using a multi-stage random sampling method. Cognitive status was assessed using Mini Mental State Examination (MMSE) questionnaire, sleep quality using Pittsburgh Sleep Quality Index (PSQI) and SDB was assessed using No-SAS scale, respectively. Multi-variable logistic regression was applied to examine the association of sleep quality and cognitive performance. Subgroup analyses were performed in different age groups, and in those with and without SDB.

Results
Finally, 30,872 participants aged 47.5 ± 13.8 years with 53.5% women were enrolled, of whom 32.4% had poor sleep quality and 18.6% had low cognitive performance. Compared with good sleepers, subjects with poor sleep quality exhibited significantly higher presence of low cognitive performance (23.7% vs 16.2%, P < 0.001). Poor sleepers revealed 1.26 (95%CI: 1.16,1.36), 1.26 (1.08,1.46) and 1.25 (1.14,1.37) fold odds for low cognitive performance in general population and in subjects with and without self-reported SDB respectively. Stratified by age and SDB, the association was observed in young and middle-aged group without SDB (OR = 1.44, 95%CI: 1.30,1.59) and in the elderly group with SDB (OR = 1.30, 95%CI: 1.07,1.58).

Conclusions
Sleep quality is in a negative association with cognitive performance in general population independent of SDB, implying improvement of sleep disturbances is a potential objective of intervention strategies for cognitive protection at population level.
Anterior cervical corpectomy and fusion with stand-alone cages in patients with multilevel degenerative cervical spine disease is safe
Authors: Tohamy Mohamed H. , Osterhoff Georg , Abdelgawaad Ahmed Shawky , Ezzati Ali , Heyde Christoph-E. 
Published: January 2022

Abstract
Background
In case of spinal cord compression behind the vertebral body, anterior cervical corpectomy and fusion (ACCF) proves to be a more feasible approach than cervical discectomy. The next step was the placement of an expandable titanium interbody in order to restore the vertebral height. The need for additional anterior plating with ACCF has been debatable and such technique has been evaluated by very few studies. The objective of the study is to evaluate radiographic and clinical outcomes in patients with multilevel degenerative cervical spine disease treated by stand-alone cages for anterior cervical corpectomy and fusion (ACCF).

Methods
Thirty-one patients (66.5 ± 9.75 years, range 53–85 years) were analyzed. Visual Analog Scale (VAS) and the 10-item Neck Disability Index (NDI) were assessed preoperatively and during follow-up on a regular basis after surgery and after one year at least. Assessment of radiographic fusion, subsidence, and lordosis measurement of Global cervical lordosis (GCL); fusion site lordosis (FSL); the anterior interbody space height (ant. DSH); the posterior interbody space height (post. DSH); the distance of the cage to the posterior wall of the vertebral body (CD) were done retrospectively. Mean clinical and radiographic follow-up was 20.0 ± 4.39 months.

Results
VAS-neck (p = 0.001) and VAS-arm (p < 0.001) improved from preoperatively to postoperatively. The NDI improved at the final follow-up (p < 0.001). Neither significant subsidence of the cages nor significant loss of lordotic correction were seen. All patients showed a radiographic union of the surgically addressed segments at the last follow up.

Conclusions
Application of a stand-alone expandable cage in the cervical spine after one or two-level ACCF without additional posterior fixation or anterior plating is a safe procedure that results in fusion. Neither significant subsidence of the cages nor significant loss of lordotic correction were seen.

Trial registration
Retrospectively registered. According to the Decision of the ethics committee, Jena on 25th of July 2018, that this study doesn’t need any registration. https://www.laek-thueringen.de/aerzte/ethikkommission/registrierung/.
Hybrid surgery with PEEK rods for lumbar degenerative diseases: a 2-year follow-up study
Authors: Zhao Yao , Xu Beiyu , Qi Longtao , Li Chunde , Yue Lei , Yu Zhengrong , Wang Shijun , Sun Haolin 
Published: January 2022

Abstract
Background
Finite element analyses and biomechanical tests have shown that PEEK rods promote fusion and prevent adjacent segment degeneration. The purpose of this study was to evaluate the effects and complications of hybrid surgery with PEEK rods in lumbar degenerative diseases.

Methods
From January 2015-December 2017, 28 patients who underwent lumbar posterior hybrid surgery with PEEK rods were included in the study. The patients were diagnosed with lumbar disc herniation, lumbar spinal stenosis, or degenerative grade I spondylolisthesis. Before the operation and at the last follow-up, the patients completed lumbar anteroposterior and lateral X-ray, dynamic X-ray, MRI examinations. In addition, at the last follow-up the patients also completed lumbar CT examinations. The radiographic parameters, clinical visual analog scale (VAS) score and Oswestry disability index (ODI) score were compared.

Results
The average age of the patients was 44.8 ± 12.6 years, and the average follow-up duration was 26.4 ± 3.6 months. The VAS score improved from 6.3 ± 1.6 to 1.0 ± 0.9, and the ODI score decreased from 38.4 ± 10.8 to 6.8 ± 4.6. The fusion rate of the fused segment was 100%. There were no significant changes in the modified Pfirrmann classifications or disc height index for the nonfused segments and the upper adjacent segments from pre- to postoperatively. No cases of screw loosening, broken screws, broken rods or other mechanical complications were found.

Conclusion
Hybrid surgery with PEEK rods for lumbar degenerative diseases can yield good clinical results and effectively reduce the incidence of complications such as adjacent segment diseases.