bluuebunny/crossref_metadata_2025 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

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

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

Background

Recent 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.

Methods

A 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.

Results

The 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).

Conclusions

Parents 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

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

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

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

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

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

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

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

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.
Spatially varying effects of measured confounding variables on disease risk
Authors: Wu Chih-Chieh , Chu Yun-Hsuan , Shete Sanjay , Chen Chien-Hsiun
Published: November 2021

Background

The presence of considerable spatial variability in incidence intensity suggests that risk factors are unevenly distributed in space and influence the geographical disease incidence distribution and pattern. As most human common diseases that challenge investigators are complex traits and as more factors associated with increased risk are discovered, statistical spatial models are needed that investigate geographical variability in the association between disease incidence and confounding variables and evaluate spatially varying effects on disease risk related to known or suspected risk factors. Information on geography that we focus on is geographical disease clusters of peak incidence and paucity of incidence.

Methods

We proposed and illustrated a statistical spatial model that incorporates information on known or hypothesized risk factors, previously detected geographical disease clusters of peak incidence and paucity of incidence, and their interactions as covariates into the framework of interaction regression models. The spatial scan statistic and the generalized map-based pattern recognition procedure that we recently developed were both considered for geographical disease cluster detection. The Freeman-Tukey transformation was applied to improve normality of distribution and approximately stabilize the variance in the model. We exemplified the proposed method by analyzing data on the spatial occurrence of sudden infant death syndrome (SIDS) with confounding variables of race and gender in North Carolina.

Results

The analysis revealed the presence of spatial variability in the association between SIDS incidence and race. We differentiated spatial effects of race on SIDS incidence among previously detected geographical disease clusters of peak incidence and incidence paucity and areas outside the geographical disease clusters, determined by the spatial scan statistic and the generalized map-based pattern recognition procedure. Our analysis showed the absence of spatial association between SIDS incidence and gender.

Conclusion

The application to the SIDS incidence data demonstrates the ability of our proposed model to estimate spatially varying associations between disease incidence and confounding variables and distinguish spatially related risk factors from spatially constant ones, providing valuable inference for targeted environmental and epidemiological surveillance and management, risk stratification, and thorough etiologic studies of disease.
Moderately trained male football players, compared to sedentary male adults, exhibit anatomical but not functional cardiac remodelling, a cross-sectional study
Authors: Engvall Jan E. , Aneq Meriam Åström , Nylander Eva , Brudin Lars , Maret Eva
Published: November 2021

Background

Elite athletes have been the subject of great interest, but athletes at an intermediate level of physical activity have received less attention in respect to the presence of cardiac enlargement and/or hypertrophy. We hypothesized that playing football, often defined as demanding less endurance components than running or cycling, would still induce remodelling similar to sports with a dominating endurance component.

Methods

23 male football players, age 25+/− 3.9 yrs. underwent exercise testing, 2D- and 3D- echocardiography and cardiac magnetic resonance (CMR). The results were compared with a control group of engineering students of similar age. The athletes exercised 12 h/week and the control subjects 1 h/week, p < 0.001.

Results

The football players achieved a significantly higher maximal load at the exercise test (380 W vs 300 W, p < 0.001) as well as higher calculated maximal oxygen consumption, (49.7 vs 37.4 mL x kg− 1 x min− 1, p < 0.001) compared to the sedentary group. All left ventricular (LV) volumes assessed by 3DEcho and CMR, as well as CMR left atrial (LA) volume were significantly higher in the athletes (3D-LVEDV 200 vs 154 mL, CMR-LVEDV 229 vs 185 mL, CMR-LA volume 100 vs 89 mL, p < 0.001, p = 0.002 and p = 0.009 respectively). LVEF and RVEF, LV strain by CMR or by echo did not differentiate athletes from sedentary participants. Right ventricular (RV) longitudinal strain, LA and right atrial (RA) strain by CMR all showed similar results in the two groups.

Conclusion

Moderately trained intermediate level football players showed anatomical but not functional cardiac remodelling compared to sedentary males.
Melatonin enhances SIRT1 to ameliorate mitochondrial membrane damage by activating PDK1/Akt in granulosa cells of PCOS
Authors: Zheng Bo , Meng Junan , Zhu Yuan , Ding Min , Zhang Yuting , Zhou Jianjun
Published: November 2021

Mitochondrial injury in granulosa cells (GCs) is associated with the pathophysiological mechanism of polycystic ovary syndrome (PCOS). Melatonin reduces the mitochondrial injury by enhancing SIRT1 (NAD-dependent deacetylase sirtuin-1), while the mechanism remains unclear. Mitochondrial membrane potential is a universal selective indicator of mitochondrial function. In this study, mitochondrial swelling and membrane defect mitochondria in granulosa cells were observed from PCOS patients and DHT-induced PCOS-like mice, and the cytochrome C level in the cytoplasm and the expression of BAX (BCL2-associated X protein) in mitochondria were significantly increased in GCs, with p-Akt decreased, showing mitochondrial membrane was damaged in GCs of PCOS. Melatonin treatment decreased mitochondrial permeability transition pore (mPTP) opening and increased the JC-1 (5,5′,6,6′-tetrachloro1,1′,3,3′-tetramethylbenzimidazolylcarbocyanine iodide) aggregate/monomer ratio in the live KGN cells treated with DHT, indicating melatonin mediates mPTP to increase mitochondrial membrane potential. Furthermore, we found melatonin decreased the levels of cytochrome C and BAX in DHT-induced PCOS mice. PDK1/Akt played an essential role in improving the mitochondrial membrane function, and melatonin treatment increased p-PDK 1 and p-Akt in vivo and in vitro. The SIRT1 was also increased with melatonin treatment, while knocking down SIRT1 mRNA inhibiting the protective effect of melatonin to activate PDK1/Akt. In conclusion, melatonin enhances SIRT1 to ameliorate mitochondrial membrane damage by activating PDK1/Akt in granulosa cells of PCOS.
Improving peer review of systematic reviews by involving librarians and information specialists: protocol for a randomized controlled trial
Authors: Rethlefsen Melissa L. , Schroter Sara , Bouter Lex M. , Moher David , Ayala Ana Patricia , Kirkham Jamie J. , Zeegers Maurice P.
Published: November 2021

Background

Problems continue to exist with the reporting quality and risk of bias in search methods and strategies in systematic reviews and related review types. Peer reviewers who are not familiar with what is required to transparently and fully report a search may not be prepared to review the search components of systematic reviews, nor may they know what is likely to introduce bias into a search. Librarians and information specialists, who have expertise in searching, may offer specialized knowledge that would help improve systematic review search reporting and lessen risk of bias, but they are underutilized as methodological peer reviewers.

Methods

This study will evaluate the effect of adding librarians and information specialists as methodological peer reviewers on the quality of search reporting and risk of bias in systematic review searches. The study will be a pragmatic randomized controlled trial using 150 systematic review manuscripts submitted to BMJ and BMJ Open as the unit of randomization. Manuscripts that report on completed systematic reviews and related review types and have been sent for peer review are eligible. For each manuscript randomized to the intervention, a librarian/information specialist will be invited as an additional peer reviewer using standard practices for each journal. First revision manuscripts will be assessed in duplicate for reporting quality and risk of bias, using adherence to 4 items from PRISMA-S and assessors’ judgements on 4 signaling questions from ROBIS Domain 2, respectively. Identifying information from the manuscripts will be removed prior to assessment.

Discussion

The primary outcomes for this study are quality of reporting as indicated by differences in the proportion of adequately reported searches in first revision manuscripts between intervention and control groups and risk of bias as indicated by differences in the proportions of first revision manuscripts with high, low, and unclear bias. If the intervention demonstrates an effect on search reporting or bias, this may indicate a need for journal editors to work with librarians and information specialists as methodological peer reviewers.

Trial registration

Open Science Framework. Registered on June 17, 2021, at 10.17605/OSF.IO/W4CK2.
“I took it off most of the time 'cause I felt comfortable”: unmasking, trusted others, and lessons learned from a coronavirus disease 2019 reinfection: a case report
Authors: Dariotis Jacinda K. , Sloane Stephanie M. , Smith Rebecca Lee
Published: November 2021

Background

Severe acute respiratory syndrome coronavirus 2 reinfection prevalence is unknown. It is essential to understand reinfection symptoms and, importantly, the lived experience.

Case presentation

Case study design is the best method for understanding this contemporary pandemic and rare occurrence of reinfections. A 19-year-old White Non-Hispanic woman presented with presumed severe acute respiratory syndrome coronavirus 2 reinfection 6 weeks after initially mild symptomatic infection and consistent repeat negative results. Real-time reverse-transcription polymerase chain reaction from saliva was used for detection. Twice-weekly saliva samples were collected (a) before initial infection, (b) resumed on day 10 after initial infection until reinfection was detected, and (c) resumed on day 10 post-reinfection. A 1.5-hour virtual interview was conducted, transcribed, and independently analyzed by two researchers. Four themes emerged: (1) perceived invincibility or inevitability and subsequent immunity increases risk of transmission via inconsistent preventive behaviors; (2) normalcy desires, trusted others, and implicit social pressures to not wear masks and distance increase one’s coronavirus disease 2019 risk; (3) physical symptoms are more severe with reinfection compared with first infection; and (4) mental health sequelae (trauma and stigma) are more severe and enduring than physical health outcomes.

Conclusions

Unmasked social interactions contradicting public health recommendations were rationalized by social circle members with heavy reliance on feeling asymptomatic, lacking a positive test (testing negative or not testing), or attributing symptoms to allergies. Stigma of testing positive and consequences of not conforming to social group behaviors is overwhelming and creates pressure to take risks. This case study provides insights and lessons learned relevant for public health messaging and continued preventive behaviors.
Exosome-associated host–pathogen interaction: a potential effect of biofilm formation
Authors: Lahiri Dibyajit , Nag Moupriya , Dey Ankita , Sarkar Tanmay , Pattnaik Smaranika , Ghosh Sougata , Edinur Hisham Atan , Pati Siddhartha , Kari Zulhisyam Abdul , Ray Rina Rani
Published: November 2021

Exosomes being non-ionized micro-vesicles with a size range of 30–100 nm possess the ability to bring about intracellular communication and intercellular transport of various types of cellular components like miRNA, mRNA, DNA, and proteins. This is achieved through the targeted transmission of various inclusions to nearby or distant tissues. This is associated with the effective communication of information to bring about changes in physiological properties and functional attributes. The extracellular vesicles (EVs), produced by fungi, parasites, and bacteria, are responsible to bring about modulation/alteration of the immune responses exerted by the host body. The lipids, nucleic acids, proteins, and glycans of EVs derived from the pathogens act as the ligands of different families of pattern recognition receptors of the host body. The bacterial membrane vesicles (BMVs) are responsible for the transfer of small RNA species, along with other types of noncoding RNA thereby playing a key role in the regulation of the host immune system. Apart from immunomodulation, the BMVs are also responsible for bacterial colonization in the host tissue, biofilm formation, and survival therein showing antibiotic resistance, leading to pathogenesis and virulence. This mini-review would focus on the role of exosomes in the development of biofilm and consequent immunological responses within the host body along with an analysis of the mechanism associated with the development of resistance.
A comprehensive overview of the genetic diversity in Thylamys elegans (Didelphimorphia: Didelphidae): establishing the phylogeographic determinants
Authors: Boric-Bargetto Dusan , Zúñiga-Reinoso Álvaro , Inostroza-Michel Oscar , Rodríguez-Serrano Enrique , González-Acuña Daniel , Palma R. Eduardo , Hernández Cristián E.
Published: November 2021

Background

For the genus Thylamys, the rivers have been reported as barriers to dispersal, limiting current and historical distribution of its lineages. We hypothesized that the Maipo river has affected the genetic structure of northern and southern lineages of Thylamys elegans, recovering a phylogenetic relationships with reciprocally monophyletic sister groups on opposite river banks. We evaluated the role of other rivers in the Mediterranean zone of Chile as historical and recent modulators of the biogeographic processes of this species.

Methods

We applied a phylogeographic approach, using the cytochrome-b mitochondrial gene for 93 individuals of T. elegans, from 37 localities in a latitudinal gradient between 21°25’ and 35˚56’S, encompassing a geographic area between the Atacama Desert and most of the Mediterranean Chilean zone.

Results

The phylogenetics results recovered six lineages within T. elegans: Thylamys elegans elegans, Thylamys elegans coquimbensis, the Loa lineage and three other lineages not described previously (Aconcagua, South 1 and South 2). We suggest that following rivers play a role like primary barrier: the Maipo river in the genetic differentiation of northern and southern ancestral lineages, and the Mataquito river and its tributary Teno river for the South 1 and South 2 lineages. On the other hand, the Quilimarí river preserve the genetic divergence in T. e. coquimbensis and Aconcagua lineage and the Aconcagua river in Aconcagua lineage and T. e. elegans acting like secondary barriers.

Conclusions

We concluded that the genetic diversity and biogeographic history of T. elegans was shaped by mountain glaciers, changes in river water levels during the Pleistocene glaciations and hyperaridity, promoting the differentiation and persistance of the T. elegans lineages.
Synthaser: a CD-Search enabled Python toolkit for analysing domain architecture of fungal secondary metabolite megasynth(et)ases
Authors: Gilchrist Cameron L. M. , Chooi Yit-Heng
Published: November 2021

Background

Fungi are prolific producers of secondary metabolites (SMs), which are bioactive small molecules with important applications in medicine, agriculture and other industries. The backbones of a large proportion of fungal SMs are generated through the action of large, multi-domain megasynth(et)ases such as polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs). The structure of these backbones is determined by the domain architecture of the corresponding megasynth(et)ase, and thus accurate annotation and classification of these architectures is an important step in linking SMs to their biosynthetic origins in the genome.

Results

Here we report synthaser, a Python package leveraging the NCBI’s conserved domain search tool for remote prediction and classification of fungal megasynth(et)ase domain architectures. Synthaser is capable of batch sequence analysis, and produces rich textual output and interactive visualisations which allow for quick assessment of the megasynth(et)ase diversity of a fungal genome. Synthaser uses a hierarchical rule-based classification system, which can be extensively customised by the user through a web application (http://gamcil.github.io/synthaser). We show that synthaser provides more accurate domain architecture predictions than comparable tools which rely on curated profile hidden Markov model (pHMM)-based approaches; the utilisation of the NCBI conserved domain database also allows for significantly greater flexibility compared to pHMM approaches. In addition, we demonstrate how synthaser can be applied to large scale genome mining pipelines through the construction of an Aspergillus PKS similarity network.

Conclusions

Synthaser is an easy to use tool that represents a significant upgrade to previous domain architecture analysis tools. It is freely available under a MIT license from PyPI (https://pypi.org/project/synthaser) and GitHub (https://github.com/gamcil/synthaser).
Management control systems in response to social and environmental risk in large Nordic companies
Authors: Semenova Natalia
Published: November 2021

This empirical study investigates the relationships between management control systems and social and environmental risks. Building on Simons’ Levers of Control conceptual framework, this study proposes that companies facing social and environmental risks will enhance the quality of their management control systems by integrating social and environmental elements into management control systems in order to manage the related risks. The study uses a longitudinal dataset of the 1179 largest listed Nordic companies for the period 2014–2018. The multivariate regression confirms a negative relationship between the social and environmental integration and social and environmental risks. The results indicate that the social and environmental integrated performance measurement system and strategy implementation are not congruent with the social and environmental risks that the companies face. Nordic companies have not adopted the social and environmental integrated measurement system and strategy in response to social and environmental risks. When the number of social and environmental incidents increase and companies meet high levels of social and environmental risks, their management control systems do not match the related risks. Such social and environmental integration should be improved in order to prevent wider negative implications of the incidents on the natural environment and society in large.
AddaVax Formulated with PolyI:C as a Potential Adjuvant of MDCK-based Influenza Vaccine Enhances Local, Cellular, and Antibody Protective Immune Response in Mice
Authors: Nian Xuanxuan , Zhang Jiayou , Deng Tao , Liu Jing , Gong Zheng , Lv Chuanshuo , Yao Luyao , Li Junying , Huang Shihe , Yang Xiaoming
Published: November 2021

Poor immune responses to inactivated influenza vaccine can be improved by effective and safe adjuvants to increase antibody titers and cellular protective response. In our study, AddaVax and PolyI:C combined adjuvant (AP adjuvant) were used for influenza vaccine development. After immunizing BALB/c mice and Wistar rats intramuscularly, Split inactivated H3N2 vaccine adjuvanted with AP elicited higher serum hemagglutination-inhibition antibodies and IgG titers. We demonstrated that AP induced a transient innate immune cytokines production at the injection site, induced H3N2 uptake by DCs, increased recruitment of monocytes and DCs in LNs, and promoted H3N2 vaccine migration; AP facilitated vaccines to induce a vigorous adaptive immune response. Besides, AP showed good safety as shown by lymph nodes (LNs) size, spleens index of BALB/c mice, and weight changes and C-reaction protein level of BALB/c mice and Wistar rats after repeated administration of high-dose vaccine with or without adjuvant. These findings indicate that AP is a potential novel adjuvant and can be used as a safe and effective adjuvant for MDCK-based influenza inactivated vaccine to induce cellular and antibody protective response.
“Can We Be Visible in This Culture without Becoming a Commodity?”
Authors: Horak Laura
Published: November 2021

In this interview, Disclosure director Sam Feder discusses the ambivalence of representation for trans people, their determination to hire as many trans people as possible on set, and how Disclosure evolved into the form it takes today.
An hourglass mechanism controls torpor bout length in hibernating garden dormice
Authors: Ruf Thomas , Gasch Kristina , Stalder Gabrielle , Gerritsmann Hanno , Giroud Sylvain
Published: November 2021

Hibernating mammals drastically lower their rate of oxygen consumption and body temperature (Tb) for up to several weeks, but regularly rewarm and stay euthermic for brief periods (< 30 h). It has been hypothesized that these periodic arousals are driven by the development of a metabolic imbalance during torpor, that is, the accumulation or the depletion of metabolites or the accrual of cellular damage that can be eliminated only in the euthermic state. We obtained oxygen consumption (as a proxy of metabolic rate) and Tb at 7-minute intervals over entire torpor-arousal cycles in the garden dormouse (Eliomys quercinus). Torpor bout duration was highly dependent on mean oxygen consumption during the torpor bout. Oxygen consumption during torpor, in turn, was elevated by Tb, which fluctuated only slightly in dormice kept at∼3-8°C. This corresponds to a well-known effect of higher Tb on shortening torpor bout lengths in hibernators. Arousal duration was independent from prior torpor length, but arousal mean oxygen consumption increased with prior torpor Tb. These results, particularly the effect of torpor oxygen consumption on torpor bout length, point to an hourglass mechanism of torpor control, i.e., the correction of a metabolic imbalance during arousal. This conclusion is in line with previous comparative studies providing evidence for significant interspecific inverse relationships between the duration of torpor bouts and metabolism in torpor. Thus, a simple hourglass mechanism is sufficient to explain torpor/arousal cycles, without the need to involve non-temperature-compensated circadian rhythms.
Thermal–metabolic phenotypes of the lizard Podarcis muralis differ across elevation, but converge in high-elevation hypoxia
Authors: Bodensteiner Brooke L. , Gangloff Eric J. , Kouyoumdjian Laura , Muñoz Martha M. , Aubret Fabien
Published: November 2021

In response to a warming climate, many montane species are shifting upslope to track the emergence of preferred temperatures. Characterizing patterns of variation in metabolic, physiological and thermal traits along an elevational gradient, and the plastic potential of these traits, is necessary to understand current and future responses to abiotic constraints at high elevations, including limited oxygen availability. We performed a transplant experiment with the upslope-colonizing common wall lizard (Podarcis muralis) in which we measured nine aspects of thermal physiology and aerobic capacity in lizards from replicate low- (400 m above sea level, ASL) and high-elevation (1700 m ASL) populations. We first measured traits at their elevation of origin and then transplanted half of each group to extreme high elevation (2900 m ASL; above the current elevational range limit of this species), where oxygen availability is reduced by ∼25% relative to sea level. After 3 weeks of acclimation, we again measured these traits in both the transplanted and control groups. The multivariate thermal–metabolic phenotypes of lizards originating from different elevations differed clearly when measured at the elevation of origin. For example, high-elevation lizards are more heat tolerant than their low-elevation counterparts (counter-gradient variation). Yet, these phenotypes converged after exposure to reduced oxygen availability at extreme high elevation, suggesting limited plastic responses under this novel constraint. Our results suggest that high-elevation populations are well suited to their oxygen environments, but that plasticity in the thermal–metabolic phenotype does not pre-adapt these populations to colonize more hypoxic environments at higher elevations.
Uniportal Thoracoscopic Single-Direction Basal Subsegmentectomy (Left S10a+ci): Trans-Inferior-Pulmonary-Ligament Approach
Authors: Liu Chengwu , Wang Wenping , Mei Jiandong , Zhu Yunke , Pu Qiang , Liu Lunxu
Published: November 2021

Thoracoscopic segmentectomy and subsegmentectomy have been widely accepted for the treatment of peripheral small lung cancers. Thoracoscopic basal subsegmentectomy, especially when performed through a uniportal procedure, is extremely technically challenging, and therefore there are seldom reports of its technical details. In this article, we present a uniportal thoracoscopic left S10a+ci subsegmentectomy following the single-direction strategy through the inferior pulmonary ligament approach.