bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterologous expression of heat stress-responsive AtPLC9 confers heat tolerance in transgenic rice
Authors: Liu Yuliang , Liu Xinye , Wang Xue , Gao Kang , Qi Weiwei , Ren Huimin , Hu Haorui , Sun Daye , Bai Jiaoteng , Zheng Shuzhi
Published: November 2020

Background

As global warming becomes increasingly severe, it is urgent that we enhance the heat tolerance of crops. We previously reported that Arabidopsis thaliana PHOSPHOINOSITIDE-SPECIFIC PHOSPHOLIPASE C9 (AtPLC9) promotes heat tolerance.

Results

In this study, we ectopically expressed AtPLC9 in rice to examine its potential to improve heat tolerance in this important crop. Whereas AtPLC9 did not improve rice tolerance to salt, drought or cold, transgenic rice did exhibit greater heat tolerance than the wild type. High-throughput RNA-seq revealed extensive and dynamic transcriptome reprofiling in transgenic plants after heat stress. Moreover, the expression of some transcription factors and calcium ion-related genes showed specific upregulation in transgenic rice after heat stress, which might contribute to the enhanced heat tolerance.

Conclusions

This study provides preliminary guidance for using AtPLC9 to improve heat tolerance in cereal crops and, more broadly, highlights that heterologous transformation can assist with molecular breeding.
Effects of a multicomponent high intensity exercise program on physical function and health-related quality of life in older adults with or at risk of mobility disability after discharge from hospital: a randomised controlled trial
Authors: Sunde Sylvia , Hesseberg Karin , Skelton Dawn A. , Ranhoff Anette Hylen , Pripp Are Hugo , Aarønæs Marit , Brovold Therese
Published: November 2020

Background

Many older people suffer from mobility limitations and reduced health-related quality of life (HRQOL) after discharge from hospital. A consensus regarding the most effective exercise-program to optimize physical function and HRQOL after discharge is lacking. This study investigates the effects of a group-based multicomponent high intensity exercise program on physical function and HRQOL in older adults with or at risk of mobility disability after discharge from hospital.

Methods

This single blinded parallel group randomised controlled trial recruited eighty-nine home dwelling older people (65–89 years) while inpatient at medical wards at a general hospital in Oslo, Norway. Baseline testing was conducted median 49 (25 percentile, 75 percentile) (26, 116) days after discharge, before randomisation to an intervention group or a control group. The intervention group performed a group-based exercise program led by a physiotherapist twice a week for 4 months. Both groups were instructed in a home-based exercise program and were encouraged to exercise according to World Health Organisation’s recommendations for physical activity in older people. The primary outcome, physical performance, was measured by the Short Physical Performance Battery (SPPB). Secondary outcomes were 6-min walk test (6MWT), Berg Balance Scale (BBS), grip strength, Body Mass Index (BMI), and HRQOL (the Short-Form 36 Health Survey (SF-36)). Data were analysed according to the intention-to-treat principle. Between-group differences were assessed using independent samples t-test.

Results

The groups were comparable at baseline. Intention-to-treat analysis showed that the intervention group improved their functional capacity (6MWT) and the physical component summary of SF-36 significantly compared to the control group. No further between group differences in change from baseline to 4 months follow-up were found.

Conclusions

A high intensity multicomponent exercise program significantly improved functional capacity and physical HRQOL in older adults with or at risk of mobility disability after discharge from hospital. The study suggests that this population can benefit from systematic group exercise after hospital-initial rehabilitation has ended.

Trial registration

ClinicalTrials.gov. NCT02905383. September 19, 2016.
Bone marrow-derived mesenchymal stem cells attenuate pulmonary inflammation and lung damage caused by highly pathogenic avian influenza A/H5N1 virus in BALB/c mice
Authors: Yudhawati Resti , Amin Muhammad , Rantam Fedik A. , Prasetya Rima R. , Dewantari Jezzy R. , Nastri Aldise M. , Poetranto Emmanuel D. , Wulandari Laksmi , Lusida Maria I. , Koesnowidagdo Soetjipto , Soegiarto Gatot , Shimizu Yohko K. , Mori Yasuko , Shimizu Kazufumi
Published: November 2020

Background

The highly pathogenic avian influenza A/H5N1 virus is one of the causative agents of acute lung injury (ALI) with high mortality rate. Studies on therapeutic administration of bone marrow-derived mesenchymal stem cells (MSCs) in ALI caused by the viral infection have been limited in number and have shown conflicting results. The aim of the present investigation is to evaluate the therapeutic potential of MSC administration in A/H5N1-caused ALI, using a mouse model.

Methods

MSCs were prepared from the bone marrow of 9 to 12 week-old BALB/c mice. An H5N1 virus of A/turkey/East Java/Av154/2013 was intranasally inoculated into BALB/c mice. On days 2, 4, and 6 after virus inoculation, MSCs were intravenously administered into the mice. To evaluate effects of the treatment, we examined for lung alveolar protein as an indicator for lung injury, PaO2/FiO2 ratio for lung functioning, and lung histopathology. Expressions of NF-κB, RAGE (transmembrane receptor for damage associated molecular patterns), TNFα, IL-1β, Sftpc (alveolar cell type II marker), and Aqp5+ (alveolar cell type I marker) were examined by immunohistochemistry. In addition, body weight, virus growth in lung and brain, and duration of survival were measured.

Results

The administration of MSCs lowered the level of lung damage in the virus-infected mice, as shown by measuring lung alveolar protein, PaO2/FiO2 ratio, and histopathological score. In the MSC-treated group, the expressions of NF-κB, RAGE, TNFα, and IL-1β were significantly suppressed in comparison with a mock-treated group, while those of Sftpc and Aqp5+ were enhanced. Body weight, virus growth, and survival period were not significantly different between the groups.

Conclusion

The administration of MSCs prevented further lung injury and inflammation, and enhanced alveolar cell type II and I regeneration, while it did not significantly affect viral proliferation and mouse morbidity and mortality. The results suggested that MSC administration was a promissing strategy for treatment of acute lung injuries caused by the highly pathogenic avian influenza A/H5N1 virus, although further optimization and combination use of anti-viral drugs will be obviously required to achieve the goal of reducing mortality.
Extensively drug-resistant Alcaligenes faecalis infection
Authors: Huang Chienhsiu
Published: November 2020

Background

Alcaligenes faecalis is usually causes opportunistic infections in humans. Alcaligenes faecalis infection is often difficult to treat due to its increased resistance to several antibiotics. The results from a clinical study of patients with Alcaligenes faecalis infection may help improve patients’ clinical care.

Methods

We conducted a retrospective analysis of all patients presenting with Alcaligenes faecalis infection from January 2014 to December 2019. The medical records of all patients were reviewed for demographic information, clinical symptoms and signs, comorbidities, use of intravenous antibiotics within the past three months, bacterial culture, antibiotics sensitivity test, and clinical outcomes.

Results

Sixty-one cases of Alcaligenes faecalis infection were seen during the study period, including 25 cases of cystitis, nine cases of diabetic foot infection, eight cases of pneumonia, seven cases of acute pyelonephritis, three cases of bacteremia, and nine cases of infection at specific sites. Thirty-seven patients (60.7%) had a history of receiving intravenous antibiotics within three months of the diagnosis. Fifty-one (83.6%) cases were mixed with other bacterial infections. Extensively drug-resistant infections have been reported since 2018. The best sensitivity rate to Alcaligenes faecalis was 66.7% for three antibiotics (imipenem, meropenem, and ceftazidime) in 2019. Two antibiotics (ciprofloxacin and piperacillin/tazobactam) sensitivity rates to A. faecalis were less than 50%.

Conclusions

The most frequent Alcaligenes faecalis infection sites, in order, are the bloodstream, urinary tract, skin and soft tissue, and middle ear. The susceptibility rate of Alcaligenes faecalis to commonly used antibiotics is decreasing. Extensively drug-resistant Alcaligenes faecalis infections have emerged.
Dengue in Western Uganda: a prospective cohort of children presenting with undifferentiated febrile illness
Authors: Boyce Ross M. , Collins Matthew , Muhindo Rabbison , Nakakande Regina , Ciccone Emily J. , Grounds Samantha , Espinoza Daniel , Zhu Yerun , Matte Michael , Ntaro Moses , Nyehangane Dan , Juliano Jonathan J. , Mulogo Edgar M.
Published: November 2020

Background

The spatial distribution and burden of dengue in sub-Saharan Africa remains highly uncertain, despite high levels of ecological suitability. The goal of this study was to describe the epidemiology of dengue among a cohort of febrile children presenting to outpatient facilities located in areas of western Uganda with differing levels of urbanicity and malaria transmission intensity.

Methods

Eligible children were first screened for malaria using rapid diagnostic tests. Children with a negative malaria result were tested for dengue using a combination NS1/IgM/IgG rapid test (SD Bioline Dengue Duo). Confirmatory testing by RT-PCR was performed in a subset of participants. Antigen-capture ELISA was performed to estimate seroprevalence.

Results

Only 6 of 1416 (0.42%) children had a positive dengue rapid test, while none of the RT-PCR results were positive. ELISA testing demonstrated reactive IgG antibodies in 28 (2.2%) participants with the highest prevalence seen at the urban site in Mbarara (19 of 392, 4.9%, p < 0.001).

Conclusions

Overall, these findings suggest that dengue, while present, is an uncommon cause of non-malarial, pediatric febrile illness in western Uganda. Further investigation into the eocological factors that sustain low-level transmission in urban settings are urgently needed to reduce the risk of epidemics.
Spiral artery blood flow during pregnancy: a systematic review and meta-analysis
Authors: Schiffer Veronique , Evers Laura , de Haas Sander , Ghossein-Doha Chahinda , Al-Nasiry Salwan , Spaanderman Marc
Published: November 2020

Background

Downstream remodeling of the spiral arteries (SpA) decreases utero-placental resistance drastically, allowing sustained and increased blood flow to the placenta under all circumstances. We systematically evaluated available reports to visualize adaptation of spiral arteries throughout pregnancy by ultra-sonographic measurements and evaluated when this process is completed.

Methods

A systematic review and meta-analysis of spiral artery flow (pulsatility index (PI), resistance index (RI) and peak systolic velocity (PSV)) was performed. English written articles were obtained from Pubmed, EMBASE and Cochrane Library and included articles were assessed on quality and risk of bias. Weighted means of Doppler indices were calculated using a random-effects model.

Results

In healthy pregnancies, PI and RI decreased from 0.80 (95% CI: 0.70–0.89) and 0.50 (95% CI: 0.47–0.54) in the first trimester to 0.50 (95% CI: 0.45–0.55, p < 0.001) and 0.39 (95% CI: 0.37–0.42, p < 0.001) in the second trimester and to 0.49 (95% CI: 0.44–0.53, p = 0.752) and 0.36 (95% CI: 0.35–0.38, p = 0.037) in the third trimester, respectively. In parallel, PSV altered from 0.22 m/s (95% CI: 0.13–0.30 m/s) to 0.28 m/s (95% CI: 0.17–0.40 m/s, p = 0.377) and to 0.25 m/s (95% CI: 0.20–0.30 m/s, p = 0.560) in the three trimesters. In absence of second and third trimester Doppler data in complicated gestation, only a difference in PI was observed between complicated and healthy pregnancies during the first trimester (1.49 vs 0.80, p < 0.001). Although individual studies have identified differences in PI between SpA located in the central part of the placental bed versus those located at its periphery, this meta-analysis could not confirm this (p = 0.349).

Conclusions

This review and meta-analysis concludes that an observed decrease of SpA PI and RI from the first towards the second trimester parallels the physiological trophoblast invasion converting SpA during early gestation, a process completed in the midst of the second trimester. Higher PI was found in SpA of complicated pregnancies compared to healthy pregnancies, possibly reflecting suboptimal utero-placental circulation. Longitudinal studies examining comprehensively the predictive value of spiral artery Doppler for complicated pregnancies are yet to be carried out.
Prenatal diagnosis of fetal microhydranencephaly: a case report and literature review
Authors: Omoto Takahiro , Takahashi Toshifumi , Fujimori Keiya , Kin Shogo
Published: November 2020

Background

The prenatal diagnosis of microhydranencephaly is important and needs to be distinguished from anencephaly, because unlike anencephaly, fetuses with microhydranencephaly can survive after birth. Herein, we report a case of microhydranencephaly that was diagnosed and distinguished from anencephaly prenatally.

Case presentation

The patient was an 18-year-old woman, 2 gravida nullipara, who presented at 15 weeks of gestation. Ultrasonography showed a normal biparietal diameter (BPD) and no major anomalies. At 23 weeks of gestation, an ultrasound examination revealed a BPD of 40 mm (-5.3 standard deviation, SD). At 29 weeks, anencephaly was suspected despite difficulty in visually examining the fetal head above the orbit. At 34 weeks, insertion of a metreurynter made it possible to observe the skull. Three-dimensional computed tomography (CT) and magnetic resonance imaging (MRI) confirmed the presence of the fetal skull, a prominent occipital bone, sloping forehead, marked microcephaly, cerebral loss, and excess cerebrospinal fluid. This allowed differentiation between microhydranencephaly and anencephaly. She delivered vaginally at 37 weeks, and the child had a birth weight of 2342 g and a head circumference of 24 cm (-5.4 SD). The baby’s head was flat above the forehead, with a suspected partial head defect. The baby received desmopressin acetate due to central diabetes insipidus 6 months after birth.

Conclusions

The use of multiple imaging modalities and physical manipulation of the fetal head are required to accurately differentiate between microhydranencephaly and anencephaly.
A meta-analysis of BRF2 as a prognostic biomarker in invasive breast carcinoma
Authors: Cabarcas-Petroski Stephanie , Meneses Patricio I. , Schramm Laura
Published: November 2020

Background

Deregulation of the RNA polymerase III specific TFIIIB subunit BRF2 occurs in subtypes of human cancers. However, correlations between BRF2 alterations and clinical outcomes in breast cancer are limited. We conducted this review to analyze BRF2 alterations in genomic data sets housed in Oncomine and cBioPortal to identify potential correlations between BRF2 alterations and clinical outcomes.

Methods

The authors queried both Oncomine and cBioPortal for alterations in BRF2 in human cancers and performed meta-analyses identifying significant correlations between BRF2 and clinical outcomes in invasive breast cancer (IBC).

Results

A meta cancer outlier profile analysis (COPA) of 715 data sets (86,733 samples) in Oncomine identified BRF2 as overexpressed in 60% of breast cancer data sets. COPA scores in IBC data sets (3594 patients) are comparable for HER2 (24.211, median gene rank 60) and BRF2 (29.656, median gene rank 36.5). Overall survival in IBC patients with BRF2 alterations (21%) is significantly decreased (p = 9.332e-3). IBC patients with BRF2 alterations aged 46 to 50 have a significantly poor survival outcome (p = 7.093e-3). Strikingly, in metastatic breast cancer, BRF2 is altered in 33% of women aged 45–50. BRF2 deletions are predominant in this age group.

Conclusion

This study suggests BRF2 may be an prognostic biomarker in invasive breast carcinoma.
A novel prognostic model predicting the long-term cancer-specific survival for patients with hypopharyngeal squamous cell carcinoma
Authors: Tang Xin , Pang Tong , Yan Wei-feng , Qian Wen-lei , Gong You-ling , Yang Zhi-gang
Published: November 2020

Background

Hypopharyngeal squamous cell carcinoma (HSCC) is a rare type of head and neck cancer with poor prognosis. However, till now, there is still no model predicting the survival outcomes for HSCC patients. We aim to develop a novel nomogram predicting the long-term cancer-specific survival (CSS) for patients with HSCC and establish a prognostic classification system.

Methods

Data of 2021 eligible HSCC patients were retrieved from the Surveillance, Epidemiology and End Results database between 2010 and 2015. We randomly split the whole cases (ratio: 7:3) into the training and the validation cohort. Cox regression as well as the Least absolute shrinkage and selection operator (LASSO) COX were used to select significant predictors of CSS. Based on the beta-value of these predictors, a novel nomogram was built. The concordance index (C-index), the calibration curve and the decision curve analysis (DCA) were utilized for the model validation and evaluation using the validation cohort.

Results

In total, cancer-specific death occurred in 974/2021 (48.2%) patients. LASSO COX indicated that age, race, T stage, N stage, M stage, surgery, radiotherapy and chemotherapy are significant prognosticators of CSS. A prognostic model based on these factors was constructed and visually presented as nomogram. The C-index of the model was 0.764, indicating great predictive accuracy. Additionally, DCA and calibration curves also demonstrated that the nomogram had good clinical effect and satisfactory consistency between the predictive CSS and actual observation. Furthermore, we developed a prognostic classification system that divides HSCC patients into three groups with different prognosis. The median CSS for HSCC patients in the favorable, intermediate and poor prognosis group was not reached, 39.0-Mo and 10.0-Mo, respectively (p < 0.001).

Conclusions

In this study, we constructed the first nomogram as well as a relevant prognostic classification system that predicts CSS for HSCC patients. We believe these tools would be helpful for clinical practice in patients’ consultation and risk group stratification.
Prevalence and correlates of adherence to the combined movement guidelines among Czech children and adolescents
Authors: Rubín Lukáš , Gába Aleš , Dygrýn Jan , Jakubec Lukáš , Materová Eliška , Vencálek Ondřej
Published: November 2020

Background

There are limited studies on the prevalence of adherence to the combined guidelines for physical activity (PA), sedentary behavior, and sleep in children and adolescents. Moreover, little is known about correlates of adherence to the guidelines. Therefore, the main aim of this study is to examine the prevalence and identify the correlates of adherence to the combined movement guidelines among children and adolescents.

Methods

A total of 355 children aged 8–13 years (44% boys) and 324 adolescents aged 14–18 years (43% boys) from the Czech Republic participated in this study. PA and sleep duration were estimated using multi-day 24-h raw data from wrist-worn accelerometers. Recreational screen time was parent proxy-reported in children and self-reported in adolescents. Seventeen potential correlates were grouped into three homogenous categories for biological and cognitive, behavioral, and family correlates. The multi-level multivariable logistic regression was applied to identify correlates of adherence to combined movement guidelines and to specific combinations of any of two recommendations.

Results

Approximately 6.5% of children and 2.2% of adolescents met all recommendations of the combined movement guidelines. In children, girls (OR = 0.4; 95% CI = 0.1–0.9) and participants with overweight or obese fathers (OR = 0.3; 95% CI = 0.1–0.7) had significantly lower odds of adherence to the combined movement guidelines. Additionally, children had higher odds of meeting specific combinations of two recommendations if they reported regular fruit and vegetable intake, participated in organized PA, or if their fathers had a university degree. Meanwhile, paternal overweight and obesity, and high sleep efficiency were associated with lower odds of meeting specific combinations of recommendations. In adolescents, sex, fruit and vegetable intake, organized PA, and active play were correlates of meeting specific combinations of any two recommendations.

Conclusions

A low proportion of children and adolescents met the combined movement guidelines and several correlates related to family were identified. Family is a key source of influence for healthy movement behaviors during childhood and adolescence.
Correction to: Mesoglycan for pain control after open excisional HAEMOrrhoidectomy (MeHAEMO): an observational multicentre study on behalf of the Italian Society of Colorectal Surgery (SICCR)
Authors:   the MeHAEMO Working Group, Gallo G. , Di Saverio S. , Clerico G. , Sturiale A . , Manigrasso M. , Luc A. Realis , Trompetto M. , Sammarco G.
Published: November 2020

An amendment to this paper has been published and can be accessed via the original article.
Influence of orthodontic treatment with premolar extraction on the spatial position of maxillary third molars in adult patients: a retrospective cohort cone-bean computed tomography study
Authors: Pan Fangwei , Yang Zhentao , Wang Jian , Cai Ruilie , Liu Jialing , Zhang Chenghao , Liao Wen
Published: November 2020

Background

Based on low-dose radiation Cone-bean computed tomography (CBCT) images, This study aims to establish a space coordinate system, which offers more precise and comparable evaluation on changes of maxillary third molars influenced by orthodontic treatment with premolar extraction in adults. The system suggests promising application prospect in future studies related to CBCT superimposition and evaluation for its feasibility and efficiency.

Methods

Forty-nine maxillary third molars from 27 patients (mean age, 20.78 years) were included. CBCT images were obtained before and after orthodontic treatment with premolars extracted (mean treatment duration, 31.47 months). The changes in the position, angulation, and rotation of the third molars were evaluated with a space coordinate system using four landmarks: anterior nasal spine (ANS), posterior nasal spine (PNS), left and right orbitales.

Results

After orthodontic treatment, the third molars moved forward (adjusted mean, 1.44 mm) (p < 0.001) and downward (adjusted mean, 2.87 mm) (p < 0.001) accompanied by outward rotation of the crowns (adjusted mean, 5.38°) (p = 0.001), while changes in angulation were insignificant.

Conclusions

This was the first study to systematically investigate the spatial position change of maxillary third molars in adult patients who received orthodontic treatment with premolar extraction. During the process, maxillary third molars moved downward and forward accompanied by outward rotation of the crowns. Orthodontists should take tooth movement potential into consideration when making extraction plans.
Perception and belief in oral health among Karen ethnic group living along Thai-Myanmar border, Thailand
Authors: Wai Yan Myint Thu Sai , Ngeonwiwatkul Yaowaluk , Maneekan Pannamas , Phuanukoonnon Suparat
Published: November 2020

Background

Utilization of oral health services has been low among rural populations in Thailand, especially for minority ethnicity populations living along the borders. The aim of this study was to increase understanding of the determinants of the underutilization of oral health services among these populations.

Methods

A qualitative study using in-depth interview and semi-structured interview was conducted among participants of Karen ethnicity living in Mae Tan Sub-district, Thasongyang District, Tak Province, Thailand. The interviews focused on exploring the participants’ perceptions of oral health problems, oral health and hygiene, and oral health-seeking behaviors. The verbatim-transcribed interviews were analyzed using thematic analysis.

Results

A total of 101 participants (50 adults and 51 children) with a Karen ethnic background took part in the interviews. Most participants could not identify oral health problems and did not perceive dental disease as a problem unless there was severe pain that could not be relieved by painkillers. The Karen ethnic community worked as subsistence farmers, and their busy daily activities consisted of farming, going to the forest to hunt and gather, performing housework, and taking care of their children. Dental health was given a lower priority compared with general health. The perceived value of primary teeth was low, which was identified as an underlying factor resulting in delayed oral health care seeking among this population. The participants had relied on self-care throughout their lifetimes, using either traditional medicines or modern painkillers to relieve toothaches. Fear of dental procedures among children was also described as a barrier to seeking dental health care.

Conclusions

This study found that the lifestyle and traditions of Karen people living in this area influence their oral health care and hygiene activities as well as their health-seeking behaviors. Further research should emphasize how to improve oral health promotion by providing necessary services and health education appropriately to Karen ethnic populations living along the Thai-Myanmar border.
Comparative effectiveness of long-term acute care hospital versus skilled nursing facility transfer
Authors: Makam Anil N. , Nguyen Oanh Kieu , Miller Michael E. , Shah Sachin J. , Kapinos Kandice A. , Halm Ethan A.
Published: November 2020

Background

Long-term acute care hospital (LTACH) use varies considerably across the U.S., which may reflect uncertainty about the effectiveness of LTACHs vs. skilled nursing facilities (SNF), the principal post-acute care alternative. Given that LTACHs provide more intensive care and thus receive over triple the reimbursement of SNFs for comparable diagnoses, we sought to compare outcomes and spending between LTACH versus SNF transfer.

Methods

Using Medicare claims linked to electronic health record (EHR) data from six Texas Hospitals between 2009 and 2010, we conducted a retrospective cohort study of patients hospitalized on a medicine service in a high-LTACH use region and discharged to either an LTACH or SNF and followed for one year. The primary outcomes included mortality, 60-day recovery without inpatient care, days at home, and healthcare spending

Results

Of 3503 patients, 18% were transferred to an LTACH. Patients transferred to LTACHs were younger (median 71 vs. 82 years), less likely to be female (50.5 vs 66.6%) and white (69.0 vs. 84.1%), but were sicker (24.3 vs. 14.2% for prolonged intensive care unit stay; median diagnosis resource intensity weight of 2.03 vs. 1.38). In unadjusted analyses, patients transferred to an LTACH vs. SNF were less likely to survive (59.1 vs. 65.0%) or recover (62.5 vs 66.0%), and spent fewer days at home (186 vs. 200). Adjusting for demographic and clinical confounders available in Medicare claims and EHR data, LTACH transfer was not significantly associated with differences in mortality (HR, 1.12, 95% CI, 0.94–1.33), recovery (SHR, 1.07, 0.93–1.23), and days spent at home (IRR, 0.96, 0.83–1.10), but was associated with greater Medicare spending ($16,689 for one year, 95% CI, $12,216–$21,162).

Conclusion

LTACH transfer for Medicare beneficiaries is associated with similar clinical outcomes but with higher healthcare spending compared to SNF transfer. LTACH use should be reserved for patients who require complex inpatient care and cannot be cared for in SNFs.
Individual and combined associations between cardiorespiratory fitness and grip strength with common mental disorders: a prospective cohort study in the UK Biobank
Authors: Kandola Aaron A. , Osborn David P. J. , Stubbs Brendon , Choi Karmel W. , Hayes Joseph F.
Published: November 2020

Background

Depression and anxiety are common mental disorders that increase physical health risks and are leading causes of global disability. Several forms of physical fitness could be modifiable risk factors for common mental disorders in the population. We examined associations between individual and combined markers of cardiorespiratory fitness and grip strength with the incidence of common mental disorders.

Methods

A 7-year prospective cohort study in 152,978 UK Biobank participants. An exercise test and dynamometer were used to measure cardiorespiratory and grip strength, respectively. We used Patient Health Questionnaire-9 and Generalised Anxiety Disorder-7 scales to estimate the incidence of common mental disorders at follow-up.

Results

Fully adjusted, longitudinal models indicated a dose-response relationship. Low and medium cardiorespiratory fitness was associated with 1.485 (95% CIs, 1.301 to 1.694, p <  0.001) and 1.141 (95% CIs, 1.005 to 1.297, p = 0.041) higher odds of depression or anxiety, compared to high cardiorespiratory fitness. Low and medium grip strength was associated with 1.381 (95% CIs, 1.315 to 1.452, p <  0.001) and 1.116 (95% CIs, 1.063 to 1.172, p <  0.001) higher odds of common mental disorder compared to high grip strength.

Individuals in the lowest group for both cardiorespiratory fitness and grip strength had 1.981 (95% CIs, 1.553 to 2.527, p <  0.001) higher odds of depression, 1.599 (95% CIs, 1.148 to 2.118, p = 0.004) higher odds of anxiety, and 1.814 (95% CIs, 1.461 to 2.252, p <  0.001) higher odds of either common mental disorder, compared to high for both types of fitness.

Conclusions

Objective cardiorespiratory and muscular fitness markers represent modifiable risk factors for common mental disorders. Public health strategies to reduce common mental disorders could include combinations of aerobic and resistance activities.
Vertebral fracture due to Actinobacillus pleuropneumoniae osteomyelitis in a weaner
Authors: Giebels Felix , Geissbühler Urs , Oevermann Anna , Grahofer Alexander , Olias Philipp , Kuhnert Peter , Maiolini Arianna , Stein Veronika Maria
Published: November 2020

Background

Osteomyelitis is relatively frequent in young pigs and a few bacterial species have been postulated to be potential causative agents. Although Actinobacillus (A.) pleuropneumoniae has been sporadically described to cause osteomyelitis, typically, actinobacillosis is characterized by respiratory symptoms. Nevertheless, subclinical infections are a challenging problem in pig herds. To the authors’ knowledge, this is the first case description that reports clinical, diagnostic imaging, pathological and histopathological findings of vertebral osteomyelitis in a pig and first describes A. pleuropneumoniae as the causative agent identified by advanced molecular methods.

Case presentation

An eight-week-old female weaner was presented with a non-ambulatory tetraparesis. The neurological signs were consistent with a lesion in the C6-T2 spinal cord segments. Imaging studies revealed a collapse of the seventh cervical vertebral body (C7) with a well demarcated extradural space-occupying mass ventrally within the vertebral canal severely compressing the spinal cord. Post-mortem examination identified an abscess and osteomyelitis of C7 and associated meningitis and neuritis with subsequent pathological fracture of C7 and compression of the spinal cord. In the microbiological analysis, A. pleuropneumoniae was identified using PCR and DNA sequence analysis.

Conclusions

A. pleuropneumoniae can be responsible for chronic vertebral abscess formation with subsequent pathological fracture and spinal cord compression in pigs.
Rational engineering of Kluyveromyces marxianus to create a chassis for the production of aromatic products
Authors: Rajkumar Arun S. , Morrissey John P.
Published: November 2020

Background

The yeast Kluyveromyces marxianus offers unique potential for industrial biotechnology because of useful features like rapid growth, thermotolerance and a wide substrate range. As an emerging alternative platform, K. marxianus requires the development and validation of metabolic engineering strategies to best utilise its metabolism as a basis for bio-based production.

Results

To illustrate the synthetic biology strategies to be followed and showcase its potential, we describe a comprehensive approach to rationally engineer a metabolic pathway in K. marxianus. We use the phenylalanine biosynthetic pathway both as a prototype and because phenylalanine is a precursor for commercially valuable secondary metabolites. First, we modify and overexpress the pathway to be resistant to feedback inhibition so as to overproduce phenylalanine de novo from synthetic minimal medium. Second, we assess native and heterologous means to increase precursor supply to the biosynthetic pathway. Finally, we eliminate branch points and competing reactions in the pathway and rebalance precursors to redirect metabolic flux to a specific product, 2-phenylethanol (2-PE). As a result, we are able to construct robust strains capable of producing over 800 mg L−1 2-PE from minimal medium.

Conclusions

The strains we constructed are a promising platform for the production of aromatic amino acid-based biochemicals, and our results illustrate challenges with attempting to combine individually beneficial modifications in an integrated platform.
Building a sanitary vulnerability map from open source data in Argentina (2010-2018)
Authors: Rosati Germán Federico , Olego Tomás Alberto , Vazquez Brust H. Antonio
Published: November 2020

Background

Designing public health policies to target the needs of specific places requires highly granular data. When geographic health statistics from official sources are absent or lacking in spatial detail, Sanitary Vulnerability metrics derived from Census and other georeferenced public data can be used to identify areas in particular need of attention. With that aim, a Vulnerability Map was developed, identifying areas with a substantial deficit in its population health coverage. As a result a novel methodology for measuring Sanitary Vulnerability is presented, that can potentially be applied to different time periods or geographies.

Methods

Census, official listings of public health facilities and crowdsourced georeferenced data are used. The Vulnerability Index is built using dimensionality reduction techniques such as Autoencoders and Non-parametric PCA.

Main results

The high resolution map shows the geographical distribution of a Sanitary Vulnerability Index, produced using official and crowdsourced open data sources, overcoming the lack of official sources on health indicators at the local level.

Conclusions

The Sanitary Vulnerability Map’s value as a tool for place specific policymaking was validated by using it to predict local health related metrics such as health coverage. Further lines of work contemplate using the Map to study the interaction between Sanitary Vulnerability and the prevalence of different diseases, and also applying its methodology in the context of other public services such as education, security, housing, etc.
Intersectionality and health-related stigma: insights from experiences of people living with stigmatized health conditions in Indonesia
Authors: Rai Sarju Sing , Peters Ruth M. H. , Syurina Elena V. , Irwanto Irwanto , Naniche Denise , Zweekhorst Marjolein B. M.
Published: November 2020

Background

Health-related stigma is a complex phenomenon, the experience of which intersects with those of other adversities arising from a diversity of social inequalities and oppressive identities like gender, sexuality, and poverty – a concept called “intersectionality”. Understanding this intersectionality between health-related stigma and other forms of social marginalization can provide a fuller and more comprehensive picture of stigma associated with health conditions. The main objective of this paper is to build upon the concept of intersectionality in health-related stigma by exploring the convergence of experiences of stigma and other adversities across the intersections of health and other forms of social oppressions among people living with stigmatized health conditions in Indonesia.

Methods

This qualitative study interviewed 40 people affected by either of four stigmatizing health conditions (HIV, leprosy, schizophrenia, and diabetes) in Jakarta and West Java, Indonesia between March and June 2018. Data was analyzed thematically using an integrative inductive-deductive framework approach.

Results

The main intersectional inequalities identified by the participants were gender and socioeconomic status (n = 21), followed by religion (n = 13), age (n = 11), co-morbidity (n = 9), disability (n = 6), and sexuality (n = 4). Based on these inequalities/identities, the participants reported of experiencing oppression because of prevailing social norms, systems, and policies (macro-level), exclusion and discrimination from societal actors (meso-level), and self-shame and stigma (micro-level). While religion and age posed adversities that negatively affected participants in macro and meso levels, they helped mitigate the negative experiences of stigma in micro level by improving self-acceptance and self-confidence.

Conclusion

This study uncovered how the experience of health-related stigma intersects with other oppressions originating from the various social inequalities in an individual’s life. The findings highlight the importance of acknowledging and understanding the multi-dimensional aspect of lives of people living with stigmatized health conditions, and warrant integrated multi-level and cross-cutting stigma reduction interventions to address the intersectional oppressions they experience.
Utilization of statins and LDL-cholesterol target attainment in Turkish patients with type 2 diabetes - a nationwide cross-sectional study (TEMD dyslipidemia study)
Authors:   TEMD Study Group, Bayram Fahri , Sonmez Alper , Haymana Cem , Sabuncu Tevfik , Dizdar Oguzhan Sitki , Gurkan Eren , Carlioglu Ayse Kargili , Agbaht Kemal , Ozdemir Didem , Demirci Ibrahim , Barcin Cem , Salman Serpil , Tetiker Tamer , Balci Mustafa Kemal , Kebapci Nur , Ersoy Canan , Yumuk Volkan , Toth Peter P. , Satman Ilhan
Published: November 2020

Background

Attaining acceptable levels of LDL Cholesterol (LDL-C) significantly improves cardiovascular (CV) outcomes in patients with type 2 diabetes mellitus (T2DM). The LDL-C target attainment and the characteristics of patients attaining these targets were investigated in this study. Furthermore, the reasons for not choosing statins and the physicians’ attitudes on the treatment of diabetic dyslipidemia were also examined.

Methods

A nationwide, cross-sectional survey was conducted in tertiary centers for diabetes management. Adult patients with T2DM, who were under follow-up for at least a year in outpatient clinics, were consecutively enrolled for the study. LDL-C goals were defined as below 70 mg/dL for patients with macrovascular complications or diabetic nephropathy, and below 100 mg/dL for other patients. Data about lipid-lowering medications were self-reported.

Results

A total of 4504 patients (female: 58.6%) were enrolled for the study. The mean HbA1c and diabetes duration was 7.73 ± 1.74% and 10.9 ± 7.5 years, respectively. The need for statin treatment was 94.9% (n = 4262); however, only 42.4% (n = 1807) of these patients were under treatment, and only 24.8% (n = 448) of these patients achieved LDL-C targets. The main reason for statin discontinuation was negative media coverage (87.5%), while only a minority of patients (12.5%) mentioned side effects. Physicians initiated lipid-lowering therapy in only 20.3% of patients with high LDL-C levels. It was observed that the female gender was a significant independent predictor of not attaining LDL-C goals (OR: 0.70, 95% CI: 0.59–0.83).

Conclusions

Less than 50 % of patients with T2DM who need statins were under treatment, and only a quarter of them attained their LDL-C targets. There exists a significant gap between the guideline recommendations and the real-world evidence in the treatment of dyslipidemia in T2DM.
Intrinsic disorder is an essential characteristic of components in the conserved circadian circuit
Authors: Pelham Jacqueline F. , Dunlap Jay C. , Hurley Jennifer M.
Published: November 2020

Introduction

The circadian circuit, a roughly 24 h molecular feedback loop, or clock, is conserved from bacteria to animals and allows for enhanced organismal survival by facilitating the anticipation of the day/night cycle. With circadian regulation reportedly impacting as high as 80% of protein coding genes in higher eukaryotes, the protein-based circadian clock broadly regulates physiology and behavior. Due to the extensive interconnection between the clock and other cellular systems, chronic disruption of these molecular rhythms leads to a decrease in organismal fitness as well as an increase of disease rates in humans. Importantly, recent research has demonstrated that proteins comprising the circadian clock network display a significant amount of intrinsic disorder.

Main body

In this work, we focus on the extent of intrinsic disorder in the circadian clock and its potential mechanistic role in circadian timing. We highlight the conservation of disorder by quantifying the extent of computationally-predicted protein disorder in the core clock of the key eukaryotic circadian model organismsDrosophila melanogaster, Neurospora crassa,andMus musculus. We further examine previously published work, as well as feature novel experimental evidence, demonstrating that the core negative arm circadian period drivers FREQUENCY (Neurospora crassa) and PERIOD-2 (PER2) (Mus musculus), possess biochemical characteristics of intrinsically disordered proteins. Finally, we discuss the potential contributions of the inherent biophysical principals of intrinsically disordered proteins that may explain the vital mechanistic roles they play in the clock to drive their broad evolutionary conservation in circadian timekeeping.

Conclusion

The pervasive conservation of disorder amongst the clock in the crown eukaryotes suggests that disorder is essential for optimal circadian timing from fungi to animals, providing vital homeostatic cellular maintenance and coordinating organismal physiology across phylogenetic kingdoms.

Graphical abstract
Bronchoalveolar Tregs are associated with duration of mechanical ventilation in acute respiratory distress syndrome
Authors: Norton Dustin L. , Ceppe Agathe , Tune Miriya K. , McCravy Matthew , Devlin Thomas , Drummond M. Bradley , Carson Shannon S. , Vincent Benjamin G. , Hagan Robert S. , Dang Hong , Doerschuk Claire M. , Mock Jason R.
Published: November 2020

Background

Foxp3+regulatory T cells (Tregs) play essential roles in immune homeostasis and repair of damaged lung tissue. We hypothesized that patients whose lung injury resolves quickly, as measured by time to liberation from mechanical ventilation, have a higher percentage of Tregs amongst CD4+T cells in either airway, bronchoalveolar lavage (BAL) or peripheral blood samples.

Methods

We prospectively enrolled patients with ARDS requiring mechanical ventilation and collected serial samples, the first within 72 h of ARDS diagnosis (day 0) and the second 48–96 h later (day 3). We analyzed immune cell populations and cytokines in BAL, tracheal aspirates and peripheral blood, as well as cytokines in plasma, obtained at the time of bronchoscopy. The study cohort was divided into fast resolvers (FR; n = 8) and slow resolvers (SR; n = 5), based on the median number of days until first extubation for all participants (n = 13). The primary measure was the percentage of CD4+T cells that were Tregs.

Results

The BAL of FR contained more Tregs than SR. This finding did not extend to Tregs in tracheal aspirates or blood. BAL Tregs expressed more of the full-length FOXP3 than a splice variant missing exon 2 compared to Tregs in simultaneously obtained peripheral blood.

Conclusion

Tregs are present in the bronchoalveolar space during ARDS. A greater percentage of CD4+cells were Tregs in the BAL of FR than SR. Tregs may play a role in the resolution of ARDS, and enhancing their numbers or functions may be a therapeutic target.
Revisiting the association between skin toxicity and better response in advanced cancer patients treated with immune checkpoint inhibitors
Authors: Gulati Nicholas , Donnelly Douglas , Qian Yingzhi , Moran Una , Johannet Paul , Zhong Judy , Osman Iman
Published: November 2020

Background

Immune checkpoint inhibition (ICI) improves survival outcomes for patients with several types of cancer including metastatic melanoma (MM), but serious immune-related adverse events requiring intervention with immunosuppressive medications occur in a subset of patients. Skin toxicity (ST) has been reported to be associated with better response to ICI. However, understudied factors, such as ST severity and potential survivor bias, may influence the strength of these observed associations.

Methods

To examine the potential confounding impact of such variables, we analyzed advanced cancer patients enrolled prospectively in a clinicopathological database with protocol-driven follow up and treated with ICI. We tested the associations between developing ST, stratified as no (n = 617), mild (n = 191), and severe (n = 63), and progression-free survival (PFS) and overall survival (OS) in univariable and multivariable analyses. We defined severe ST as a skin event that required treatment with systemic corticosteroids. To account for the possibility of longer survival associating with adverse events instead of the reverse, we treated ST as a time-dependent covariate in an adjusted model.

Results

Both mild and severe ST were significantly associated with improved PFS and OS (all P < 0.001). However, when adjusting for the time from treatment initiation to time of skin event, severe ST was not associated with PFS benefit both in univariable and multivariable analyses (P = 0.729 and P = 0.711, respectively). Receiving systemic steroids for ST did not lead to significant differences in PFS or OS compared to patients who did not receive systemic steroids.

Conclusions

Our data reveal the influence of time to event and its severity as covariates in analyzing the relationship between ST and ICI outcomes. These differences in outcomes cannot be solely explained by the use of immunosuppressive medications, and thus highlight the importance of host- and disease-intrinsic factors in determining ICI response and toxicity.

Trial registration: The patient data used in this manuscript come from patients who were prospectively enrolled in two institutional review board-approved databases at NYU Langone Health (institutional review board #10362 and #S16-00122).