bluuebunny/crossref_metadata_2025_split huggingface dataset:
Opposite effects of the triple target (DNA-PK/PI3K/mTOR) inhibitor PI-103 on the radiation sensitivity of glioblastoma cell lines proficient and deficient in DNA-PKcs
Authors: Djuzenova Cholpon S. , Fischer Thomas , Katzer Astrid , Sisario Dmitri , Korsa Tessa , Steussloff Gudrun , Sukhorukov Vladimir L. , Flentje Michael 
Published: November 2021

Abstract
Background
Radiotherapy is routinely used to combat glioblastoma (GBM). However, the treatment efficacy is often limited by the radioresistance of GBM cells.

Methods
Two GBM lines MO59K and MO59J, differing in intrinsic radiosensitivity and mutational status of DNA-PK and ATM, were analyzed regarding their response to DNA-PK/PI3K/mTOR inhibition by PI-103 in combination with radiation. To this end we assessed colony-forming ability, induction and repair of DNA damage by γH2AX and 53BP1, expression of marker proteins, including those belonging to NHEJ and HR repair pathways, degree of apoptosis, autophagy, and cell cycle alterations.

Results
We found that PI-103 radiosensitized MO59K cells but, surprisingly, it induced radiation resistance in MO59J cells. Treatment of MO59K cells with PI-103 lead to protraction of the DNA damage repair as compared to drug-free irradiated cells. In PI-103-treated and irradiated MO59J cells the foci numbers of both proteins was higher than in the drug-free samples, but a large portion of DNA damage was quickly repaired. Another cell line-specific difference includes diminished expression of p53 in MO59J cells, which was further reduced by PI-103. Additionally, PI-103-treated MO59K cells exhibited an increased expression of the apoptosis marker cleaved PARP and increased subG1 fraction. Moreover, irradiation induced a strong G2 arrest in MO59J cells (~ 80% vs. ~ 50% in MO59K), which was, however, partially reduced in the presence of PI-103. In contrast, treatment with PI-103 increased the G2 fraction in irradiated MO59K cells.

Conclusions
The triple-target inhibitor PI-103 exerted radiosensitization on MO59K cells, but, unexpectedly, caused radioresistance in the MO59J line, lacking DNA-PK. The difference is most likely due to low expression of the DNA-PK substrate p53 in MO59J cells, which was further reduced by PI-103. This led to less apoptosis as compared to drug-free MO59J cells and enhanced survival via partially abolished cell-cycle arrest. The findings suggest that the lack of DNA-PK-dependent NHEJ in MO59J line might be compensated by DNA-PK independent DSB repair via a yet unknown mechanism.
Colorectal Cancer associated with pediatric inflammatory bowel disease: a case series
Authors: Kim Min Jee , Ko Jae Sung , Shin Minsoo , Hahn Jong Woo , Moon Soo Young , Kim Hyun Young , Moon Jin Soo 
Published: November 2021

Abstract
Background
Inflammatory bowel disease (IBD) is associated with an increased risk of Colorectal cancer (CRC), and its most important risk factors are the duration and extent of the disease. Pediatric-onset inflammatory bowel disease has a tendency for a more extensive, more severe, and longer predicted disease duration than adult-onset inflammatory bowel disease. This study aimed to identify the clinical characteristics of patients with CRC related to pediatric-onset IBD and consider the appropriateness of current surveillance endoscopy recommendations for the detection of premalignant lesions and early-stage CRC.

Methods
We searched a research platform based on the SUPREME electronic medical record data-mining system to identify cases of colorectal malignancy in patients with pediatric IBD that presented between 2000 and 2020.

Results
During the follow-up, 4 (1.29 per 1000 person years) out of 443 patients with PIBD was diagnosed with CRC. The median age at diagnosis of CRC was 18.5 (range: 15–24) years, and the median period from diagnosis of IBD to CRC was 9.42 (range: 0.44–11.96) years. The sigmoid colon was the most frequent location of CRC (in 3 of the 4 cases). Adenocarcinoma was the most common histological type (in 2 of the 4 cases).

Conclusions
Patients with pediatric-onset IBD exhibited a much shorter disease duration than that of adult-onset IBD at the time of diagnosis of CRC, suggesting that surveillance endoscopy for the detection of precancerous lesions and early-stage cancer should be initiated earlier in pediatric patients than in adult patients.
Complementary and alternative medicine use among pediatrics in Palestine: a cross-sectional study
Authors: Al-Jabi Samah W. , Khader Mariam , Hamarsha Islam , Atallh Dina , Bani-Odeh Sereen , Daraghmeh Areen , Bani-Mater Shaima , Zyoud Sa’ed H. 
Published: November 2021

AbstractBackgroundRecent use of complementary and alternative medicine (CAM) is growing in children worldwide, so there is a need to evaluate CAM’s use among pediatrics in Palestine. This study aimed to estimate the prevalence of CAM use among a sample of Palestinian children, investigate the factors that affect the use of CAMs, identify the types of CAM used, and assess the purposes of using them.MethodsA cross-sectional descriptive study of parents who had children aged 6 years and below was carried out. A convenient sample of about 420 participants was collected; from Primary care to Motherhood and Childhood Centers in Nablus city in Palestine. Parents who agreed to participate were asked to answer a survey that consists mainly of closed-ended questions. The analysis was performed using SPSS version 16.0.ResultsThe use of CAM was detected in all interviewers 420 (100%). The most common treatment used was herbal therapy (n = 400, 95.2%), and anise was the most common herbal therapy used (n = 334; 79.5%). A total of 371 (88.3%) of the respondents used CAM for digestive system problems. The main reason for using CAM was making the child more comfortable (n = 365; 86.9%). Parents who are 30 years or older were significantly using more CAM than younger parents (P = 0.001). In addition, regarding the number of children in the family, parents who have five children or more used more CAM subtypes significantly more than parents with less than this number (P = 0.025). Moreover, parents living in a refugee camp used more CAM than parents who lived in urban or rural areas (P = 0.031).ConclusionsParents of children use CAM frequently. All parents used CAM, and physicians were not mainly among the sources of CAM information, and almost all parents were unaware of the side effects of CAM. Future research is necessary to direct pediatricians in formulating recommendations for children on CAM modalities, including possible risks and benefits and interactions with conventional medications.
The foundations of the working alliance in assertive community treatment teams
Authors: van Haaren M. , de Jong S. , Roeg D. P. K. 
Published: November 2021

Abstract
Background
In this study, we aimed to identify and define the fundamental components of the working alliance in multidisciplinary (Flexible) Assertive Community Treatment teams with shared caseloads, in order to support their daily practice and further research.

Methods
After reviewing the literature, concept mapping with professionals and clients was used to define the working alliance in (F) ACT teams. The resulting concept maps formed the basis for the working alliance assessment instrument, which was pilot tested with professionals and clients through cognitive interviews with a think-aloud procedure.

Results
The study led to the development of a twenty five-item assessment instrument to evaluate working alliances in multidisciplinary teams (WAM) that was comprised of three subscales: bond, task/goal and team. Two different versions were developed for clients and professionals.

Conclusions
The WAM instrument was developed to determine the quality of the working alliance in (F) ACT teams. Future research will focus on testing its psychometric properties and predictive value.
BDNF, GDNF, NGF and Klotho levels and neurocognitive functions in acute term of schizophrenia
Authors: Turkmen Betul Aslan , Yazici Esra , Erdogan Derya Guzel , Suda Mehmet Akif , Yazici Ahmet Bulent 
Published: November 2021

Abstract
Background
Klotho and its relationship with neurotrophic factors and cognition in schizophrenia has not yet been investigated. In this study, the hypothesis that the blood serum levels of BDNF, GDNF, NGF and Klotho in schizophrenia patients and healthy controls would be related to cognitive functions was investigated.

Methods
In this study, two groups were assessed: schizophrenia patients (case group) who were hospitalised in the Psychiatry Clinic of Sakarya University Training and Research Hospital and healthy volunteers (control group). The patients were evaluated on the 1st and 20th days of their hospitalisation with the Positive and Negative Syndrome Scale (PANSS), the Brief Psychiatric Rating Scale (BPRS), the General Assessment of Functioning Scale (GAF) and the Clinical Global Impression Scale (CGI). For cognitive assessment, both groups were evaluated with the Wechsler Memory Scale-Visual Production Subtest (Wechsler Memory Scale III-Visual Reproduction Subtest) and the Stroop test.

Results
BDNF, GDNF, NGF and Klotho levels were lower in schizophrenia patients than in healthy controls. In the schizophrenia patients, on the 20th day of treatment, there was a statistically significant increase in BDNF compared to the 1st day of treatment. BDNF, GDNF and Klotho showed positive correlations with some cognitive functions in the healthy controls. BDNF, GDNF, NGF and Klotho levels were intercorrelated and predictive of each other in both groups.

Conclusion
This study suggests a relationship between cognitive functions, neurotrophic factors and Klotho. Most of the results are the first of their kind in the extant literature, while other results are either similar to or divergent from those generated in previous studies. Therefore, new, enhanced studies are needed to clarify the role of Klotho and neurotrophic factors in schizophrenia.
The association between first and second wave COVID-19 mortality in Italy
Authors: Vinceti Marco , Filippini Tommaso , Rothman Kenneth J. , Di Federico Silvia , Orsini Nicola 
Published: November 2021

Abstract
Background
The relation between the magnitude of successive waves of the COVID-19 outbreak within the same communities could be useful in predicting the scope of new outbreaks.

Methods
We investigated the extent to which COVID-19 mortality in Italy during the second wave was related to first wave mortality within the same provinces. We compared data on province-specific COVID-19 2020 mortality in two time periods, corresponding to the first wave (February 24–June 30, 2020) and to the second wave (September 1–December 31, 2020), using cubic spline regression.

Results
For provinces with the lowest crude mortality rate in the first wave (February–June), i.e. < 22 cases/100,000/month, mortality in the second wave (September–December) was positively associated with mortality during the first wave. In provinces with mortality greater than 22/100,000/month during the first wave, higher mortality in the first wave was associated with a lower second wave mortality. Results were similar when the analysis was censored at October 2020, before the implementation of region-specific measures against the outbreak. Neither vaccination nor variant spread had any role during the study period.

Conclusions
These findings indicate that provinces with the most severe initial COVID-19 outbreaks, as assessed through mortality data, faced milder second waves.
A novel care guide for personalised palliative care – a national initiative for improved quality of care
Authors: Birgisdóttir Dröfn , Duarte Anette , Dahlman Anna , Sallerfors Bengt , Rasmussen Birgit H. , Fürst Carl Johan 
Published: November 2021

Abstract
Background
Even when palliative care is an integrated part of the healthcare system, the quality is still substandard for many patients and often initiated too late. There is a lack of structured guidelines for identifying and caring for patients; in particular for those with early palliative care needs. A care guide can act as a compass for best practice and support the care of patients throughout their palliative trajectory. Such a guide should both meet the needs of health care professionals and patients and families, facilitating discussion around end-of-life decision-making and enabling them to plan for the remaining time in life. The aim of this article is to describe the development and pilot testing of a novel Swedish palliative care guide.

Methods
The Swedish Palliative Care Guide (S-PCG) was developed according to the Medical Research Council framework and based on national and international guidelines for good palliative care. An interdisciplinary national advisory committee of over 90 health care professionals together with patient, family and public representatives were engaged in the process. The feasibility was tested in three pilot studies in different care settings.

Results
After extensive multi-unit and interprofessional testing and evaluation, the S-PCG contains three parts that can be used independently to identify, assess, address, follow up, and document the individual symptoms and care-needs throughout the whole palliative care trajectory. The S-PCG can provide a comprehensive overview and shared understanding of the patients’ needs and possibilities for ensuring optimal quality of life, the family included.

Conclusions
Based on broad professional cooperation, patients and family participation and clinical testing, the S-PCG provides unique interprofessional guidance for assessment and holistic care of patients with palliative care needs, promotes support to the family, and when properly used supports high-quality personalised palliative care throughout the palliative trajectory. Future steps for the S-PCG, entails scientific evaluation of the clinical impact and effect of S-PCG in different care settings – including implementation, patient and family outcomes, and experiences of patient, family and personnel.
Improved preventive care clinical decision-making efficiency: leveraging a point-of-care clinical decision support system
Authors: Laing Scott , Mercer Jay 
Published: November 2021

Abstract
Background
Electronic medical records are widely used in family practices across Canada and can improve health outcomes. However, recent reports indicate that physicians using electronic medical records work longer and have less direct patient contact which may contribute to burnout. Therefore, new and innovative digital tools are essential to reduce physician workloads and improve patient-physician interaction to address physician burnout. The objective of this study was to assess the efficiency and accuracy of clinical decision-making when using a new preventive care point-of-care clinical decision support system (CDSS). An estimate of the potential annual time savings was also determined. This study also assessed physician reported perceived usefulness and ease of use of the CDSS.

Methods
Quantitative and qualitative data were collected during this study. Each participant evaluated two simulated patient charts and identified which preventive care metrics were due. The participants recorded their decisions and the time required to assess each chart. Participants then completed a Technology Acceptance Model survey regarding the perceived usefulness and ease of use of the CDSS, which included qualitative feedback. The amount of time saved was determined and participants’ clinical decision-making accuracy was scored against current Canadian preventive care guidelines. The number of preventive care specific visits completed per year was determined using clinic billing data.

Results
The preventive care CDSS saved an average of 195.7 s of chart review time (249.5 s vs 445.2 s; P < 0.001). A total of 1520 preventive visits were performed at Primrose and Bruyère Family Medicine Centres. Extrapolated across the organization, implementation of the new tool could save 82.6 h per year. Decision-making accuracy was not affected by the new tool (78.4% vs 80.9%, P > 0.05). Participants rated the perceived ease of use and usefulness to be very high.

Conclusions
New digital tools may reduce providers’ workload without impacting clinical decision-making accuracy. Participants indicated that the preventive care CDSS was useful and easy to use. Further software development and clinical studies are required to further improve and characterize the effect this new CDSS has when implemented in clinical practice.
Challenges to the utilization of Community-based Health Planning and Services: the views of stakeholders in Yendi Municipality, Ghana
Authors: Bassoumah Bougangue , Adam Andani Mohammed , Adokiya Martin Nyaaba 
Published: November 2021

Abstract
Background
The Community-based Health Planning and Services (CHPS) is a national health reform programme that provides healthcare at the doorsteps of rural community members, particularly, women and children. It seeks to reduce health inequalities and promote equity of health outcomes. The study explored implementation and utilization challenges of the CHPS programme in the Northern Region of Ghana.

Methods
This was an observational study that employed qualitative methods to interview key informants covering relevant stakeholders. The study was guided by the systems theory. In all, 30 in-depth interviews were conducted involving 8 community health officers, 8 community volunteers, and 14 women receiving postnatal care in four (4) CHPS zones in the Yendi Municipality. The data were thematically analysed using Atlas.ti.v.7 software and manual coding system.

Results
The participants reported poor clinical attendance including delays in seeking health care, low antenatal and postnatal care visits. The barriers of the CHPS utilization include lack of transportation, poor road network, cultural beliefs (e.g. taboos of certain foods), proof of women’s faithfulness to their husbands and absence of health workers. Other challenges were poor communication networks during emergencies, and inaccessibility of ambulance service. In seeking health care, insured members of the national health insurance scheme (NHIS) still pay for services that are covered by the NHIS. We found that the CHPS compounds lack the capacity to sterilize some of their equipment, lack of incentives for Community Health Officers and Community Health Volunteers and inadequate infrastructures such as potable water and electricity. The study also observed poor coordination of interventions, inadequate equipment and poor community engagement as setbacks to the progress of the CHPS policy.

Conclusions
Clinical attendance, timing and number of antenatal and postnatal care visits, remain major concerns for the CHPS programme in the study setting. The CHPS barriers include transportation, poor road network, cost of referrals, cultural beliefs, inadequate equipment, lack of incentives and poor community engagement. There is an urgent need to address these challenges to improve the utilization of CHPS compounds and to contribute to achieving the sustainable development goals.
An HSP90 cochaperone Ids2 maintains the stability of mitochondrial DNA and ATP synthase
Authors: Jiang Pei-Heng , Hou Chen-Yan , Teng Shu-Chun 
Published: November 2021

Abstract
Background
Proteostasis unbalance and mitochondrial dysfunction are two hallmarks of aging. While the chaperone folds and activates its clients, it is the cochaperone that determines the specificity of the clients. Ids2 is an HSP90’s cochaperone controlling mitochondrial functions, but no in vivo clients of Ids2 have been reported yet.

Results
We performed a screen of the databases of HSP90 physical interactors, mitochondrial components, and mutants with respiratory defect, and identified Atp3, a subunit of the complex V ATP synthase, as a client of Ids2. Deletion of IDS2 destabilizes Atp3, and an α-helix at the middle region of Ids2 recruits Atp3 to the folding system. Shortage of Ids2 or Atp3 leads to the loss of mitochondrial DNA. The intermembrane space protease Yme1 is critical to maintaining the Atp3 protein level. Moreover, Ids2 is highly induced when cells carry out oxidative respiration.

Conclusions
These findings discover a cochaperone essentially for maintaining the stability of mitochondrial DNA and the proteostasis of the electron transport chain—crosstalk between two hallmarks of aging.
Radiological pleuroparenchymal fibroelastosis-like lesion in idiopathic interstitial pneumonias
Authors: Fujisawa Tomoyuki , Horiike Yasuoki , Egashira Ryoko , Sumikawa Hiromitsu , Iwasawa Tae , Matsushita Shoichiro , Sugiura Hiroaki , Kataoka Kensuke , Hashisako Mikiko , Yasui Hideki , Hozumi Hironao , Karayama Masato , Suzuki Yuzo , Furuhashi Kazuki , Enomoto Noriyuki , Nakamura Yutaro , Inui Naoki , Suda Takafumi 
Published: November 2021

Abstract
Background
Pleuroparenchymal fibroelastosis (PPFE) is characterised by predominant upper lobe pleural and subpleural lung parenchymal fibrosis. Radiological PPFE-like lesion has been associated with various types of interstitial lung diseases. However, the prevalence and clinical significance of radiological PPFE-like lesion in patients with idiopathic interstitial pneumonias (IIPs) are not fully understood. We aimed to determine the prevalence and clinical impact on survival of radiological PPFE-like lesion in patients with IIPs.

Methods
A post-hoc analysis was conducted using data from the Japanese nationwide cloud-based database of patients with IIPs. All the patients in the database were diagnosed as having IIPs by multidisciplinary discussion. Patients diagnosed with idiopathic PPFE were excluded. Clinical data and chest computed tomography (CT) image of 419 patients with IIPs were analysed. The presence of radiological PPFE-like lesion was independently evaluated by two chest radiologists blind to the clinical data.

Results
Of the 419 patients with IIPs, radiological PPFE-like lesions were detected in 101 (24.1%) patients, mainly in idiopathic pulmonary fibrosis (IPF) and unclassifiable IIPs, but less in idiopathic nonspecific interstitial pneumonia. Prognostic analyses revealed that radiological PPFE-like lesion was significantly associated with poor outcome in patients with IIPs, which was independent of age, IPF diagnosis and %FVC. In survival analyses, the patients with radiological PPFE-like lesions had poor survival compared with those without (log-rank, p < 0.0001). Subgroup analyses demonstrated that radiological PPFE-like lesion was significantly associated with poor survival both in patients with IPF and those with unclassifiable IIPs.

Conclusion
Radiological PPFE-like lesion is a condition that could exist in IIPs, mainly in IPF and unclassifiable IIPs. Importantly, the radiological PPFE-like lesion is a non-invasive marker to predict poor outcome in patients with IIPs, which should be carefully considered in clinical practice.