bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Locomotion Therapy With the Wearable Cyborg HAL on Bladder and Bowel Function in Acute and Chronic SCI Patients
Authors: Brinkemper Alexis , Grasmücke Dennis , Yilmaz Emre , Reinecke Felix , Schildhauer Thomas Armin , Aach Mirko
Published: April 2021

Study Design:

Retrospective survey.

Objectives:

Purpose of this study was to explore whether bowel and bladder management can be influenced by locomotion therapy with HAL Robot Suit.

Methods:

35 subjects with acute (< one year since injury, n = 13) or chronic (> one year since injury, n = 22) incomplete paraplegia (American Spinal Injury Association Impairment Scale (AIS) B, n = 1 / AIS C, n = 22 / AIS D, n = 7) or complete paraplegia (AIS A, n = 5) with zones of partial preservation (ZPP) participated. A retrospective survey was carried out asking for bowel incontinence (Wexner Score), constipation (Cleveland Clinic Constipation Scoring System (CCCS)) and bladder function (self-developed questionnaire) before and after completing a training period of 12 weeks with HAL.

Results:

Wexner Score over all patients and for group of chronic patients decreased significantly. For group of acute patients Wexner Score decreased insignificantly. Patients from both groups with higher baseline scores could decrease significantly. CCCS was insignificantly reduced for all patients, group of acute and group of chronic patients. For subgroup of chronic patients with higher baseline scores, CCCS decreased at end of training period missing out significance. The self-developed questionnaire showed an improvement in bladder function in 28.24% of all patients, 31.43% of chronic patients, and 23.08% of acute patients.

Conclusions:

Our findings show trends of enhanced bladder and bowel function following exoskeleton training. Patients with higher baseline scores in Wexner Score and CCCS seem to benefit more than those with mild to moderate scores.
Epidemiology of Foot and Ankle Injuries in NCAA Jumping Athletes in the United States During 2009-2014
Authors: Lytle Joseph B. , Parikh Kisan B. , Tarakemeh Armin , Vopat Bryan G. , Mulcahey Mary K.
Published: April 2021

Background:

Foot and ankle injuries comprise a significant proportion of all injuries sustained by National Collegiate Athletic Association (NCAA) athletes. In particular, sports that combine jumping and rapid changes in direction are associated with increased lower extremity injuries.

Purpose:

To describe the epidemiology of foot and ankle injuries in men’s and women’s jumping sports, including NCAA men’s and women’s basketball, women’s volleyball, and women’s gymnastics, during the 2009-2010 through 2013-2014 seasons.

Study Design:

Descriptive epidemiology study.

Methods:

Injury-surveillance data were obtained from the NCAA Injury Surveillance Program for the 2009-2010 through 2013-2014 seasons. Injuries were examined by mechanism, activity during injury, and participation restriction time. Injury rates per 1000 athlete-exposures (AEs), injury rate ratios, and risk ratios with 95% CIs were calculated. Reported sex differences were calculated for men’s and women’s basketball. All 95% CIs not containing 1.0 were considered statistically significant.

Results:

A total of 1136 players sustained foot and ankle injuries (483 male and 653 female) over 612,680 AEs. These injuries resulted in a combined rate of 1.85 per 1000 AEs (95% CI, 1.75-1.97). Ankle sprains were the most common injury (63.7%), with lateral ligamentous complex injuries making up 77.1% of all ankle sprains. The most common foot injury varied based on sport and sex. Ankle injury rates were higher in male versus female basketball players (injury rate ratio, 1.33 [95% CI, 1.13-1.57]), but foot injury rates did not differ. Among basketball and volleyball players, player contact during jumping was the most common injury mechanism. Female gymnasts had higher overuse injury rates than other athletes (0.49/1000 AEs [95% CI, 0.30-0.74]; P < .002). Overall, female basketball players were 1.81 times more likely to sustain an overuse injury than male basketball players (95% CI, 1.02-3.20; P = .02).

Conclusion:

The most common foot and ankle injury sustained in collegiate jumping sports was a lateral ligamentous complex ankle sprain. Injury-prevention programs focusing on ankle flexibility, strength, and proprioception may help to alleviate the injury burden and lessen severity. Improving the anticipation of contact during jumping and landing may reduce injury rates and increase player safety. The increased prevalence of overuse injuries in female collegiate athletes competing in jumping sports necessitates further investigation to reduce injury rates through prevention and training programs.
The Pendulum of Majoritarianism: Turkey’s Governmental Self-Identity and Turkish–Egyptian Relations
Authors: Tetik Mustafa Onur
Published: April 2021

Turkey’s relations with Egypt abruptly hit rock bottom following the Egyptian army’s ousting of Mohammed Morsi in July 2013. Despite significant political fluctuations between the two countries, there is a gap in academic literature about addressing alterations in Turkish–Egyptian relations holistically. To this end, this article proposes that Turkey’s volatile relationship with the Egyptian governments since the so-called Arab Spring is partially a reflection of broader institutional changes in Turkey’s domestic settings. One of these salient changes is the discursive transformation of Turkish national self-perception. This article shows how Turkey’s new governmental self-understanding of “majoritarianism” manifests in its relations with Egypt. It asserts that this transformation in the governmental perception of the national-self made Turkey’s policies on Egypt, which oscillate between one extreme to another, “conceivable/thinkable” via the medium of national identity discourses. It shows the interplay between the governmental identity discourses of the Justice and Development Party (AKP) elites and Turkey’s policies on Egypt in the institutional/non-discursive foreign policy field.
Binge-Like Ethanol Drinking Increases Otx2, Wnt1, and Mdk Gene Expression in the Ventral Tegmental Area of Adult Mice
Authors: Coles Cassandre , Lasek Amy W
Published: April 2021

Alcohol use disorder is associated with pathophysiological changes in the dopaminergic system. Orthodenticle homeobox 2 (OTX2) is a transcription factor important for the development of dopaminergic neurons residing in the ventral tegmental area (VTA), a critical region of the brain involved in drug reinforcement. Previous studies have demonstrated that ethanol exposure during embryonic development reduces Otx2 mRNA levels in the central nervous system. We hypothesized that levels of OTX2 would be altered by binge-like ethanol consumption in adult animals. To test this, Otx2 mRNA and protein levels in the mouse VTA were measured by quantitative real-time PCR and western blotting, respectively, after mice drank ethanol for 4 days in a procedure that elicits binge levels of ethanol consumption (drinking in the dark). Expression of known and putative OTX2 transcriptional target genes ( Sema3c, Wnt1, and Mdk) were also measured in the VTA after ethanol drinking. Otx2 mRNA and protein levels were elevated in the VTA 24 hours after the fourth drinking session and there was a corresponding increase in the expression of Mdk transcript. Interestingly, Wnt1 transcript was elevated in the VTA immediately after the fourth drinking session but returned to control levels 24 hours later. We next investigated if viral-mediated reduction of Otx2 in the mouse VTA would alter ethanol or sucrose intake. Lentiviral vectors expressing a shRNA targeting Otx2 or a control shRNA were injected into the VTA and mice were tested in the drinking in the dark protocol for ethanol and sucrose drinking. Reducing levels of OTX2 in the VTA did not alter ethanol or sucrose consumption. One limitation is that the extent of OTX2 reduction may not have been sufficient. Although OTX2 in the VTA may not play a role in binge-like drinking in adult mice, OTX2 could contribute to ethanol-induced transcriptional changes in this region.
Identification of a novel subset of alveolar type 2 cells enriched in PD-L1 and expanded following pneumonectomy
Authors: Ahmadvand Negah , Khosravi Farhad , Lingampally Arun , Wasnick Roxana , Vazquez-Armendariz Ana Ivonne , Carraro Gianni , Heiner Monika , Rivetti Stefano , Lv Yuqing , Wilhelm Jochen , Gunther Andreas , Herold Susanne , Al Alam Denise , Chen Chengshui , Minoo Parviz , Zhang Jin-San , Bellusci Saverio
Published: April 2021

Alveolar type 2 (AT2) cells are heterogeneous cells, with specialised AT2 subpopulations within this lineage exhibiting stem cell properties. However, the existence of quiescent, immature cells within the AT2 lineage that are activated during lung regeneration is unknown.

SftpcCreERT2/+;tdTomatoflox/floxmice were used for the labelling of AT2 cells and labelled subpopulations were analysed by flow cytometry, quantitative PCR, assay for transposase-accessible chromatin using sequencing (ATAC-seq), gene arrays, pneumonectomy and culture of precision-cut lung slices. Single-cell RNA-sequencing (scRNA-seq) data from human lungs were analysed.

In mice, we detected two distinct AT2 subpopulations, with low tdTomato level (TomLow) and high tdTomato level (TomHigh). TomLowcells express lower levels of the AT2 differentiation markersFgfr2bandEtv5, while TomHigh, asbona fidemature AT2 cells, show higher levels ofSftpc,Sftpb,Sftpa1,Fgfr2bandEtv5expression. ATAC-seq analysis indicates that TomLowand TomHighcells constitute two distinct cell populations, with specific silencing ofSftpc,Rosa26and cell cycle gene loci in the TomLowpopulation. Upon pneumonectomy, the number of TomLowbut not TomHighcells increases and TomLowcells show upregulated expression ofFgfr2b,Etv5,Sftpc,Ccnd1andCcnd2compared to Sham. TomLowcells overexpress programmed cell death 1 ligand 1 (PD-L1), an immune inhibitory membrane receptor ligand, which is used by flow cytometry to differentially isolate these two subpopulations. In the human lung, data mining of a recent scRNA-seq AT2 data set demonstrates the existence of aPD-L1Pospopulation. Therefore, we have identified a novel population of AT2 quiescent, immature progenitor cells in mouse that expand upon pneumonectomy and we have provided evidence for the existence of such cells in human.
A SNP of HD-ZIP I transcription factor leads to distortion of trichome morphology in cucumber (Cucumis sativus L.)
Authors: Zhang Leyu , Lv Duo , Pan Jian , Zhang Keyan , Wen Haifan , Chen Yue , Du Hui , He Huanle , Cai Run , Pan Junsong , Wang Gang
Published: April 2021

Background

Trichomes are excellent model systems for the analysis of cell differentiation and play essential roles in plant protection. From cucumber inbred line ‘WD1’, we identified an EMS-induced trichome abnormally developing mutant,nps, which exhibited smaller, denser and no pyramid-shaped head trichomes.

Results

Using F2and BC1populations constructed from a cross betweennpsand ‘9930’, the genetic analysis showed that thenpstrait is controlled by a single recessive nuclear gene. We identifiedCsNpsby map-based cloning with 576 individuals of the F2population generated from the cross ofnpsand inbred line ‘9930’. TheCsNpswas located at a 13.4-kb genomic region on chromosome 3, which region contains three predicted genes. Sequence analysis showed that only one single nucleotide mutation (C → T) between 9930 andnpswas found in the second exon ofCsa3G748220, a plant-specific class I HD-Zip gene. The result of allelism test also indicated thatnpsis a novel allelic mutant ofMict(Micro-trichome). Thus,npswas renamedmict-L130F. By comparing the transcriptome ofmict-L130Fvs WD1 and 06–2 (mict) vs 06–1 (wildtype, near-isogenic line of 06–2), several potential target genes that may be related to trichome development were identified.

Conclusions

Our results demonstrate thatMict-L130Fis involved in the morphogenesis of trichomes. Map-based cloning of theMict-L130Fgene could promote the study of trichome development in cucumber.
Pinpointing regulatory protein phosphatase 2A subunits involved in beneficial symbiosis between plants and microbes
Authors: Averkina Irina O. , Harris Muhammad , Asare Edward Ohene , Hourdin Berenice , Paponov Ivan A. , Lillo Cathrine
Published: April 2021

Background

PROTEIN PHOSPHATASE 2A (PP2A) expression is crucial for the symbiotic association between plants and various microbes, and knowledge on these symbiotic processes is important for sustainable agriculture. Here we tested the hypothesis that PP2A regulatory subunits, especiallyB’φandB’θ,are involved in signalling between plants and mycorrhizal fungi or plant-growth promoting bacteria.

Results

Treatment of tomato plants (Solanum lycopersicum)with the plant growth-promoting rhizobacteria (PGPR)Azospirillum brasilenseandPseudomonas simiaeindicated a role for the PP2A B’θ subunit in responses to PGPR. Arbuscular mycorrhizal fungi influencedB’θtranscript levels in soil-grown plants with canonical arbuscular mycorrhizae. In plant roots, transcripts ofB’φwere scarce under all conditions tested and at a lower level than all other PP2A subunit transcripts. In transformed tomato plants with 10-fold enhancedB’φexpression, mycorrhization frequency was decreased in vermiculite-grown plants. Furthermore, the highB’φexpression was related to abscisic acid and gibberellic acid responses known to be involved in plant growth and mycorrhization.B’φoverexpressor plants showed less vigorous growth, and although fruits were normal size, the number of seeds per fruit was reduced by 60% compared to the original cultivar.

Conclusions

Expression of theB’θgene in tomato roots is strongly influenced by beneficial microbes. Analysis ofB’φoverexpressor tomato plants and established tomato cultivars substantiated a function ofB’φin growth and development in addition to a role in mycorrhization.
Nationwide cross-sectional study of antimicrobial stewardship and antifungal stewardship programs in inpatient settings in Japan
Authors: Moriyama  Yuki , Ishikane Masahiro , Kusama Yoshiki , Matsunaga Nobuaki , Tajima Taichi , Hayakawa Kayoko , Ohmagari Norio
Published: April 2021

Background

To prevent antimicrobial resistance, both antimicrobial stewardship (AMS) and antifungal stewardship (AFS) in inpatient settings are needed in small/middle-sized hospitals as well as large hospitals.

Methods

We conducted the web-based, self-administered, nationwide cross-sectional study regarding AMS and AFS in inpatient settings in Japan, targeting hospitals that participated in a hospital epidemiology workshop conducted in July 2018. The questionnaire was composed of intervention protocols for use of broad-spectrum antimicrobials and antifungals within 7 or 28 d of beginning usage. These broad-spectrum antimicrobial and antifungal protocols were compared between large (≥501beds) and small/middle-sized (≤500 beds) hospitals.

Results

Of 240 hospitals surveyed, 39 (16%; 18 large and 21 small/middle-sized) responded. The number of hospitals that intervened in the use of broad-spectrum antimicrobials within 7 and 28 d were 17 (44%) and 34 (87%), respectively; those that intervened for antifungals were 3 (8%) and 10 (26%), respectively. Interventions for use of broad-spectrum antimicrobials within 7 d were significantly more frequent in small/middle-sized hospitals compared to large hospitals [13 (61. 9%) vs. 4 (22. 2%), odds ratio = 5.7, 95% confidence interval = 1.4–23.3, p = 0.023].

Conclusions

Small/middle-sized hospitals had more frequent interventions within 7 d of broad-spectrum antimicrobial use than large hospitals. More effort to improve AFS is needed among all hospitals.
Online respondent-driven detection for enhanced contact tracing of close-contact infectious diseases: benefits and barriers for public health practice
Authors: Helms Yannick B. , Hamdiui Nora , Eilers Renske , Hoebe Christian , Dukers-Muijrers Nicole , van den Kerkhof Hans , Timen Aura , Stein Mart L.
Published: April 2021

Background

Online respondent-driven detection (RDD) is a novel method of case finding that can enhance contact tracing (CT). However, the advantages and challenges of RDD for CT have not yet been investigated from the perspective of public health professionals (PHPs). Therefore, it remains unclear if, and under what circumstances, PHPs are willing to apply RDD for CT.

Methods

Between March and April 2019, we conducted semi-structured interviews with Dutch PHPs responsible for CT in practice. Questions were derived from the ‘diffusion of innovations’ theory. Between May and June 2019, we distributed an online questionnaire among 260 Dutch PHPs to quantify the main qualitative findings. Using different hypothetical scenarios, we assessed anticipated advantages and challenges of RDD, and PHPs’ intention to apply RDD for CT.

Results

Twelve interviews were held, and 70 PHPs completed the online questionnaire. A majority of questionnaire respondents (71%) had a positive intention towards using RDD for CT. Anticipated advantages of RDD were ‘accommodating easy and autonomous participation in CT of index cases and contact persons’, and ‘reaching contact persons more efficiently’. Anticipated challenges were ‘limited opportunities for PHPs to support, motivate, and coordinate the execution of CT’, ‘not being able to adequately convey measures to index cases and contact persons’, and ‘anticipated unrest among index cases and contact persons’. Circumstances under which PHPs anticipated RDD applicable for CT included index cases and contact persons being reluctant to share information directly with PHPs, digitally skilled and literate persons being involved, and large scale CT. Circumstances under which PHPs anticipated RDD less applicable for CT included severe consequences of missing information or contact persons for individual or public health, involvement of complex or impactful measures for index cases and contact persons, and a disease being perceived as severe or sensitive by index cases and their contact persons.

Conclusions

PHPs generally perceived RDD as a potentially beneficial method for public health practice, that may help overcome challenges present in traditional CT, and could be used during outbreaks of infectious diseases that spread via close contact. The circumstances under which CT is performed, appear to strongly influence PHPs’ intention to use RDD for CT.
A hierarchical procedure to select intrauterine and extrauterine factors for methodological validation of preterm birth risk estimation
Authors: Della Rosa Pasquale Anthony , Miglioli Cesare , Caglioni Martina , Tiberio Francesca , Mosser Kelsey H.H. , Vignotto Edoardo , Canini Matteo , Baldoli Cristina , Falini Andrea , Candiani Massimo , Cavoretto Paolo
Published: April 2021

Background

Etiopathogenesis of preterm birth (PTB) is multifactorial, with a universe of risk factors interplaying between the mother and the environment. It is of utmost importance to identify the most informative factors in order to estimate the degree of PTB risk and trace an individualized profile. The aims of the present study were: 1) to identify all acknowledged risk factors for PTB and to select the most informative ones for defining an accurate model of risk prediction; 2) to verify predictive accuracy of the model and 3) to identify group profiles according to the degree of PTB risk based on the most informative factors.

Methods

The Maternal Frailty Inventory (MaFra) was created based on a systematic review of the literature including 174 identified intrauterine (IU) and extrauterine (EU) factors. A sample of 111 pregnant women previously categorized in low or high risk for PTB below 37 weeks, according to ACOG guidelines, underwent the MaFra Inventory. First, univariate logistic regression enabled p-value ordering and the Akaike Information Criterion (AIC) selected the model including the most informative MaFra factors. Second, random forest classifier verified the overall predictive accuracy of the model. Third, fuzzy c-means clustering assigned group membership based on the most informative MaFra factors.

Results

The most informative and parsimonious model selected through AIC included Placenta Previa, Pregnancy Induced Hypertension, Antibiotics, Cervix Length, Physical Exercise, Fetal Growth, Maternal Anxiety, Preeclampsia, Antihypertensives. The random forest classifier including only the most informative IU and EU factors achieved an overall accuracy of 81.08% and an AUC of 0.8122. The cluster analysis identified three groups of typical pregnant women, profiled on the basis of the most informative IU and EU risk factors from a lower to a higher degree of PTB risk, which paralleled time of birth delivery.

Conclusions

This study establishes a generalized methodology for building-up an evidence-based holistic risk assessment for PTB to be used in clinical practice. Relevant and essential factors were selected and were able to provide an accurate estimation of degree of PTB risk based on the most informative constellation of IU and EU factors.
Comparing the characteristics and predicting the survival of patients with head and neck melanoma versus body melanoma: a population-based study
Authors: Ding Yuxin , Jiang Runyi , Chen Yuhong , Jing Jing , Yang Xiaoshuang , Wu Xianjie , Zhang Xiaoyang , Xu Jiali , Xu Piaopiao , LiuHuang Shu Chen , Lu Zhongfa
Published: April 2021

Background

Previous studies reported cutaneous melanoma in head and neck (HNM) differed from those in other regions (body melanoma, BM). Individualized tools to predict the survival of patients with HNM or BM remain insufficient. We aimed at comparing the characteristics of HNM and BM, developing and validating nomograms for predicting the survival of patients with HNM or BM.

Methods

The information of patients with HNM or BM from 2004 to 2015 was obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The HNM group and BM group were randomly divided into training and validation cohorts. We used the Kaplan-Meier method and multivariate Cox models to identify independent prognostic factors. Nomograms were developed via the rms and dynnom packages, and were measured by the concordance index (C-index), the area under the curve (AUC) of the receiver operating characteristic (ROC) curve and calibration plots.

Results

Of 70,605 patients acquired, 21% had HNM and 79% had BM. The HNM group contained more older patients, male sex and lentigo maligna melanoma, and more frequently had thicker tumors and metastases than the BM group. The 5-year cancer-specific survival (CSS) and overall survival (OS) rates were 88.1 ± 0.3% and 74.4 ± 0.4% in the HNM group and 92.5 ± 0.1% and 85.8 ± 0.2% in the BM group, respectively. Eight variables (age, sex, histology, thickness, ulceration, stage, metastases, and surgery) were identified to construct nomograms of CSS and OS for patients with HNM or BM. Additionally, four dynamic nomograms were available on web. The internal and external validation of each nomogram showed high C-index values (0.785–0.896) and AUC values (0.81–0.925), and the calibration plots showed great consistency.

Conclusions

The characteristics of HNM and BM are heterogeneous. We constructed and validated four nomograms for predicting the 3-, 5- and 10-year CSS and OS probabilities of patients with HNM or BM. These nomograms can serve as practical clinical tools for survival prediction and individual health management.
Predicting short stay total hip arthroplasty by use of the timed up and go-test
Authors: Oosting Ellen , Kapitein Paul J. C. , de Vries Suzan V. , Breedveld Ellen
Published: April 2021

Background

One of the most important steps before implementing short stay total hip arthroplasty (THA) is establishing patient criteria. Most existing criteria are mainly based on medical condition, but as physical functioning is associated with outcome after THA, we aim to evaluate the added value of a measure of physical functioning to predict short-stay THA.

Methods

We used retrospective data of 1559 patients who underwent an anterior THA procedure. Logistic regression analyses were performed to study the predictive value of preoperative variables among which preoperative physical functioning by use of the Timed Up and Go test (TUG) for short stay THA (< 36 h). The receiver operating characteristic (ROC) curve and Youden Index were used to define a cutoff point for TUG associated with short stay THA.

Results

TUG was significantly associated with LOS (OR 0.84, 95%CI 0.82–0.87) as analyzed by univariate regression analysis. In multivariate regression, a model with the TUG had a better performance with an AUC of 0.77 (95%CI 0.74–0.79) and a R2 of 0.27 compared to the basic model (AUC 0.75, 95%CI 0.73–0.77, R2 0.24). Patients with a preoperative TUG less than 9.7 s had an OR of 4.01 (95%CI 3.19–5.05) of being discharged within 36 h.

Conclusions

Performance based physical functioning, measured by the TUG, is associated with short stay THA. This knowledge will help in the decision-making process for the planning and expectations in short stay THA protocols with the advantage that the TUG is a simple and fast instrument to be carried out.
Fresher with flavour: young women smokers’ constructions and experiences of menthol capsule cigarettes and regular cigarettes
Authors: Gilbert E. , Ewald A.
Published: April 2021

Background

Flavour capsule cigarettes are one of the fastest growing segments of the tobacco market, and there is evidence that Australian young people are increasingly using menthol flavoured capsule cigarettes. This qualitative research examines how young women construct and experience menthol flavour capsule cigarettes as part of their smoking practices, and explores the perceived differences between menthol capsule cigarettes and regular cigarettes. Semi-structured face-to-face in-depth interviews were conducted with 41 Australian young women smokers, using a constructivist grounded theory approach.

Results

Findings reveal that the perceived fresh and improved taste of menthol and the ability to customise the smoking process positively contributed to young women’s experiences of smoking menthol capsule cigarettes. In particular, menthol capsule flavour cigarettes were constructed by the young women as “fresh”, “light” and “minty”, and “popping” the menthol capsule allowed the young women to personalise their smoking experience.

Conclusion

These results indicate that specific public health campaigns and legislation should be developed to counter the powerfully alluring effects and the innovative appeal of menthol capsule cigarettes.
Transcriptomic biomarker pathways associated with death in HIV-infected patients with cryptococcal meningitis
Authors: Vlasova-St Louis Irina , Musubire Abdu K. , Meya David B. , Nabeta Henry W. , Mohei Hesham , Boulware David R. , Bohjanen Paul R.
Published: April 2021

Background

Cryptococcal meningitis (CM) is a major cause of death in HIV-infected patients in sub-Saharan Africa. Many CM patients experience cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS), which is often fatal. We sought to identify transcriptomic biomarker pathways in peripheral blood that are associated with or predict the development of death or fatal C-IRIS among patients with CM who were enrolled in the Cryptococcal Optimal ART Timing Trial.

Methods

We assessed peripheral blood gene expression using next-generation RNA sequencing in 4 groups of patients with CM: (1) no C-IRIS or Death; (2) C-IRIS survivors; (3) fatal C-IRIS; (4) Death without C-IRIS. Gene expression was assessed at the time of ART initiation, at 1, 4, and 8 weeks on ART, and at the time of C-IRIS events.

Results

We identified 12 inflammatory and stress response pathways, including interferon type 1 signaling, that were upregulated at the time of ART initiation in patients with future fatal C-IRIS, as compared with survivors. The upregulation of transcripts involved in innate immunity (inflammasome, Toll-like receptor signaling), was observed at the time of fatal or nonfatal C-IRIS events. At the time of fatal C-IRIS events, numerous transcripts within fMLP, Rho family GTPases, HMGB1, and other acute phase response signaling pathways were upregulated, which reflects the severity of inflammation and systemic oxidative stress. Patients who died without recognized C-IRIS also had increased expression of pathways associated with oxidative stress and tissue damage.

Conclusions

Our results showed that overactivated innate immunity, involving Toll-like receptor/inflammasome pathways, and inflammation-induced oxidative stress, are associated with fatal outcomes. The results of this study provide insight into the molecular drivers of death and fatal C-IRIS to inform future diagnostic test development or guide targeted treatments.
Analysis of equity and social inclusiveness of national urban development policies and strategies through the lenses of health and nutrition
Authors: Onwujekwe Obinna , Mbachu Chinyere Ojiugo , Ajaero Chukwuedozie , Uzochukwu Benjamin , Agwu Prince , Onuh Juliana , Orjiakor Charles Tochukwu , Odii Aloysius , Mirzoev Tolib
Published: April 2021

Introduction

Rapid urbanization increases competition for scarce urban resources and underlines the need for policies that promote equitable access to resources. This study examined equity and social inclusion of urban development policies in Nigeria through the lenses of access to health and food/nutrition resources.

Method

Desk review of 22 policy documents, strategies, and plans within the ambit of urban development was done. Documents were sourced from organizational websites and offices. Data were extracted by six independent reviewers using a uniform template designed to capture considerations of access to healthcare and food/nutrition resources within urban development policies/plans/strategies in Nigeria. Emerging themes on equity and social inclusion in access to health and food/nutirition resources were identified and analysed.

Results

Access to health and food/nutrition resources were explicit in eight (8) and twelve (12) policies/plans, respectively. Themes that reflect potential policy contributions to social inclusion and equitable access to health resources were: Provision of functional and improved health infrastructure; Primary Health Care strengthening for quality health service delivery; Provision of safety nets and social health insurance; Community participation and integration; and Public education and enlightenment. With respect to nutrition resources, emergent themes were: Provision of accessible and affordable land to farmers; Upscaling local food production, diversification and processing; Provision of safety nets; Private-sector participation; and Special considerations for vulnerable groups.

Conclusion

There is sub-optimal consideration of access to health and nutrition resources in urban development policies in Nigeria. Equity and social inclusivity in access to health and nutrition resources should be underscored in future policies.
Habitat influences skeletal morphology and density in the snailfishes (family Liparidae)
Authors: Gerringer M. E. , Dias A. S. , von Hagel A. A. , Orr J. W. , Summers A. P. , Farina S.
Published: April 2021

We tested the hypothesis that deep-sea fishes have poorly mineralized bone relative to shallower-dwelling species using data from a single family that spans a large depth range. The family Liparidae (snailfishes, Cottiformes) has representatives across the entire habitable depth range for bony fishes (0 m–> 8000 m), making them an ideal model for studying depth-related trends in a confined phylogeny. We used micro-computed tomography (micro-CT) scanning to test three aspects of skeletal reduction in snailfishes (50 species) across a full range of habitat depths: 1) reduction of structural dimensions, 2) loss of skeletal elements, and 3) reduction in bone density. Using depth data from the literature, we found that with increasing depth, the length of the dentary, neurocranium, and suborbital bones decreases. The ventral suction disk decreases width with increasing maximum habitat depth and is lost entirely in some deeper-living taxa, though not all. Although visual declines in bone density in deeper-living taxa were evident across full skeletons, individual densities of the lower jaw, vertebra, suction disk, hypural plate, and otoliths did not significantly decline with any depth metric. However, pelagic and polar taxa tended to show lower density bones compared to other species in the family. We propose that skeletal reductions allow snailfishes to maintain neutral buoyancy at great depths in the water column, while supporting efficient feeding and locomotion strategies. These findings suggest that changes in skeletal structure are non-linear and are driven not only by hydrostatic pressure, but by other environmental factors and by evolutionary ancestry, calling the existing paradigm into question.
Radiomics for prediction of radiation-induced lung injury and oncologic outcome after robotic stereotactic body radiotherapy of lung cancer: results from two independent institutions
Authors: Bousabarah Khaled , Blanck Oliver , Temming Susanne , Wilhelm Maria-Lisa , Hoevels Mauritius , Baus Wolfgang W. , Ruess Daniel , Visser-Vandewalle Veerle , Ruge Maximilian I. , Treuer Harald , Kocher Martin
Published: April 2021

Objectives

To generate and validate state-of-the-art radiomics models for prediction of radiation-induced lung injury and oncologic outcome in non-small cell lung cancer (NSCLC) patients treated with robotic stereotactic body radiation therapy (SBRT).

Methods

Radiomics models were generated from the planning CT images of 110 patients with primary, inoperable stage I/IIa NSCLC who were treated with robotic SBRT using a risk-adapted fractionation scheme at the University Hospital Cologne (training cohort). In total, 199 uncorrelated radiomic features fulfilling the standards of the Image Biomarker Standardization Initiative (IBSI) were extracted from the outlined gross tumor volume (GTV). Regularized models (Coxnet and Gradient Boost) for the development of local lung fibrosis (LF), local tumor control (LC), disease-free survival (DFS) and overall survival (OS) were built from either clinical/ dosimetric variables, radiomics features or a combination thereof and validated in a comparable cohort of 71 patients treated by robotic SBRT at the Radiosurgery Center in Northern Germany (test cohort).

Results

Oncologic outcome did not differ significantly between the two cohorts (OS at 36 months 56% vs. 43%, p = 0.065; median DFS 25 months vs. 23 months, p = 0.43; LC at 36 months 90% vs. 93%, p = 0.197). Local lung fibrosis developed in 33% vs. 35% of the patients (p = 0.75), all events were observed within 36 months. In the training cohort, radiomics models were able to predict OS, DFS and LC (concordance index 0.77–0.99, p < 0.005), but failed to generalize to the test cohort. In opposite, models for the development of lung fibrosis could be generated from both clinical/dosimetric factors and radiomic features or combinations thereof, which were both predictive in the training set (concordance index 0.71– 0.79, p < 0.005) and in the test set (concordance index 0.59–0.66, p < 0.05). The best performing model included 4 clinical/dosimetric variables (GTV-Dmean, PTV-D95%, Lung-D1ml, age) and 7 radiomic features (concordance index 0.66, p < 0.03).

Conclusion

Despite the obvious difficulties in generalizing predictive models for oncologic outcome and toxicity, this analysis shows that carefully designed radiomics models for prediction of local lung fibrosis after SBRT of early stage lung cancer perform well across different institutions.
Oncolytic viruses encoding bispecific T cell engagers: a blueprint for emerging immunovirotherapies
Authors: Heidbuechel Johannes P. W. , Engeland Christine E.
Published: April 2021

Bispecific T cell engagers (BiTEs) are an innovative class of immunotherapeutics that redirect T cells to tumor surface antigens. While efficacious against certain hematological malignancies, limited bioavailability and severe toxicities have so far hampered broader clinical application, especially against solid tumors. Another emerging cancer immunotherapy are oncolytic viruses (OVs) which selectively infect and replicate in malignant cells, thereby mediating tumor vaccination effects. These oncotropic viruses can serve as vectors for tumor-targeted immunomodulation and synergize with other immunotherapies. In this article, we discuss the use of OVs to overcome challenges in BiTE therapy. We review the current state of the field, covering published preclinical studies as well as ongoing clinical investigations. We systematically introduce OV-BiTE vector design and characteristics as well as evidence for immune-stimulating and anti-tumor effects. Moreover, we address additional combination regimens, including CAR T cells and immune checkpoint inhibitors, and further strategies to modulate the tumor microenvironment using OV-BiTEs. The inherent complexity of these novel therapeutics highlights the importance of translational research including correlative studies in early-phase clinical trials. More broadly, OV-BiTEs can serve as a blueprint for diverse OV-based cancer immunotherapies.
The effectiveness of PROLOTHERAPY for recalcitrant Medial TIBIAL Stress Syndrome: a prospective consecutive CASE series
Authors: Padhiar Nat , Curtin Mark , Aweid Osama , Aweid Bashaar , Morrissey Dylan , Chan Otto , Malliaras Peter , Crisp Tom
Published: April 2021

Background

Medial tibial stress syndrome (MTSS) is one of the most common lower leg injuries in sporting populations. It accounts for between 6 and 16% of all running injuries, and up to 53% of lower leg injuries in military recruits. Various treatment modalities are available with varying degrees of success. In recalcitrant cases, surgery is often the only option.

Objective

To evaluate whether ultrasound‐guided injection of 15% dextrose for treatment of recalcitrant MTSS decreases pain and facilitates a return to desired activity levels for those who may otherwise be considering surgery or giving up the sport.

Method

The study design was a prospective consecutive case series involving eighteen patients: fifteen male and three female; (mean age = 31.2 years) with recalcitrant MTSS. They were referred from sports injury clinics across the UK, having failed all available conservative treatment.

Intervention

An ultrasound‐guided sub‐periosteal injection of 15% dextrose was administered by the same clinician (NP) along the length of the symptomatic area. Typically, 1 mL of solution was injected per cm of the symptomatic area.

Main outcome measures

Pain was assessed using a 10‐cm visual analog scale (VAS) at baseline, short‐term, medium‐term (mean 18 weeks), and long‐term (mean 52 weeks) follow‐up. Symptom resolution and return to activity were measured using a Likert scale at medium and long‐term follow‐up. Statistical analyses were performed using SPSS for Mac version 19.0.0 (IBM, New York, NY, US). The Shapiro‐Wilk test was used to evaluate the normality of the distribution of data. Friedman's non‐parametric test was used to compare the within‐patient treatment response over time. Post‐hoc Wilcoxon signed‐rank tests with Bonferroni corrections were performed to determine VAS average pain response to treatment over five paired periods.

Results

Patients reported a significant (p < 0.01) reduction in median VAS pain score at medium and long‐term follow‐up compared to baseline. Median improvement per patient was 4.5/10. Patients rated their condition as ‘much improved’ at medium‐term follow‐up and the median return to sports score was ‘returned to desired but not pre‐injury level’ at medium‐term and long‐term follow‐up. No adverse events were reported.

Conclusions

Ultrasound‐guided 15% dextrose prolotherapy injection has a significant medium‐term effect on pain in MTSS. This benefit may be maintained long‐term; however, more robust trials are required to validate these findings in the absence of controls.

Clinical relevance

Clinicians should consider the use of ultrasound‐guided injection of 15% dextrose as a viable treatment option to reduce pain and aid return to activity for patients with recalcitrant MTSS.
Adverse events associated with administration of vasopressor medications through a peripheral intravenous catheter: a systematic review and meta-analysis
Authors: Owen Victoria S. , Rosgen Brianna K. , Cherak Stephana J. , Ferland Andre , Stelfox Henry T. , Fiest Kirsten M. , Niven Daniel J.
Published: April 2021

Background

It is unclear whether vasopressors can be safely administered through a peripheral intravenous (PIV). Systematic review and meta-analysis methodology was used to examine the incidence of local anatomic adverse events associated with PIV vasopressor administration in patients of any age cared for in any acute care environment.

Methods

MEDLINE, EMBASE, CINAHL, the Cochrane Central Register of controlled trials, and the Database of Abstracts of Reviews of Effects were searched without restriction from inception to October 2019. References of included studies and related reviews, as well as relevant conference proceedings were also searched. Studies were included if they were: (1) cohort, quasi-experimental, or randomized controlled trial study design; (2) conducted in humans of any age or clinical setting; and (3) reported on local anatomic adverse events associated with PIV vasopressor administration. Risk of bias was assessed using the Revised Cochrane risk-of-bias tool for randomized trials or the Joanna Briggs Institute checklist for prevalence studies where appropriate. Incidence estimates were pooled using random effects meta-analysis. Subgroup analyses were used to explore sources of heterogeneity.

Results

Twenty-three studies were included in the systematic review, of which 16 and 7 described adults and children, respectively. Meta-analysis from 11 adult studies including 16,055 patients demonstrated a pooled incidence proportion of adverse events associated with PIV vasopressor administration as 1.8% (95% CI 0.1–4.8%,I2 = 93.7%). In children, meta-analysis from four studies and 388 patients demonstrated a pooled incidence proportion of adverse events as 3.3% (95% CI 0.0–10.1%,I2 = 82.4%). Subgroup analyses did not detect any statistically significant effects associated with stratification based on differences in clinical location, risk of bias or design between studies, PIV location and size, or vasopressor type or duration. Most studies had high or some concern for risk of bias.

Conclusion

The incidence of adverse events associated with PIV vasopressor administration is low. Additional research is required to examine the effects of PIV location and size, vasopressor type and dose, and patient characteristics on the safety of PIV vasopressor administration.
A verified genomic reference sample for assessing performance of cancer panels detecting small variants of low allele frequency
Authors: Jones Wendell , Gong Binsheng , Novoradovskaya Natalia , Li Dan , Kusko Rebecca , Richmond Todd A. , Johann Donald J. , Bisgin Halil , Sahraeian Sayed Mohammad Ebrahim , Bushel Pierre R. , Pirooznia Mehdi , Wilkins Katherine , Chierici Marco , Bao Wenjun , Basehore Lee Scott , Lucas Anne Bergstrom , Burgess Daniel , Butler Daniel J. , Cawley Simon , Chang Chia-Jung , Chen Guangchun , Chen Tao , Chen Yun-Ching , Craig Daniel J. , del Pozo Angela , Foox Jonathan , Francescatto Margherita , Fu Yutao , Furlanello Cesare , Giorda Kristina , Grist Kira P. , Guan Meijian , Hao Yingyi , Happe Scott , Hariani Gunjan , Haseley Nathan , Jasper Jeff , Jurman Giuseppe , Kreil David Philip , Łabaj Paweł , Lai Kevin , Li Jianying , Li Quan-Zhen , Li Yulong , Li Zhiguang , Liu Zhichao , López Mario Solís , Miclaus Kelci , Miller Raymond , Mittal Vinay K. , Mohiyuddin Marghoob , Pabón-Peña Carlos , Parsons Barbara L. , Qiu Fujun , Scherer Andreas , Shi Tieliu , Stiegelmeyer Suzy , Suo Chen , Tom Nikola , Wang Dong , Wen Zhining , Wu Leihong , Xiao Wenzhong , Xu Chang , Yu Ying , Zhang Jiyang , Zhang Yifan , Zhang Zhihong , Zheng Yuanting , Mason Christopher E. , Willey James C. , Tong Weida , Shi Leming , Xu Joshua
Published: April 2021

Background

Oncopanel genomic testing, which identifies important somatic variants, is increasingly common in medical practice and especially in clinical trials. Currently, there is a paucity of reliable genomic reference samples having a suitably large number of pre-identified variants for properly assessing oncopanel assay analytical quality and performance. The FDA-led Sequencing and Quality Control Phase 2 (SEQC2) consortium analyze ten diverse cancer cell lines individually and their pool, termed Sample A, to develop a reference sample with suitably large numbers of coding positions with known (variant) positives and negatives for properly evaluating oncopanel analytical performance.

Results

In reference Sample A, we identify more than 40,000 variants down to 1% allele frequency with more than 25,000 variants having less than 20% allele frequency with 1653 variants in COSMIC-related genes. This is 5–100× more than existing commercially available samples. We also identify an unprecedented number of negative positions in coding regions, allowing statistical rigor in assessing limit-of-detection, sensitivity, and precision. Over 300 loci are randomly selected and independently verified via droplet digital PCR with 100% concordance. Agilent normal reference Sample B can be admixed with Sample A to create new samples with a similar number of known variants at much lower allele frequency than what exists in Sample A natively, including known variants having allele frequency of 0.02%, a range suitable for assessing liquid biopsy panels.

Conclusion

These new reference samples and their admixtures provide superior capability for performing oncopanel quality control, analytical accuracy, and validation for small to large oncopanels and liquid biopsy assays.
Establishment of a Japanese version of the Sick, Control, One Stone, Fat, and Food (SCOFF) questionnaire for screening eating disorders in university students
Authors: Hosoda Yutaka , Ohtani Toshiyuki , Hanazawa Hisashi , Tanaka Mami , Kimura Hiroshi , Ohsako Noriaki , Hashimoto Tasuku , Kobori Osamu , Iyo Masaomi , Nakazato Michiko
Published: April 2021

Objective

This study aimed to validate the Sick, Control, One stone, Fat, and Food (SCOFF) questionnaire in relation to the Eating Disorders Examination Questionnaire (EDE-Q) and to examine the appropriateness of a question concerning weight loss among Japanese university students. The psychometric properties of the two Japanese versions were determined among 649 Japanese college students. The original version (SCOFF-O) employed the original item 3, whereas the revised version (SCOFF-2.5) modified the item to “Have you recently lost more than 2.5 kg within three months?” Validity was tested relative to EDE-Q.

Results

The test–retest reliabilities of SCOFF-O and SCOFF-2.5 were 0.52 and 0.57, while the correlations of SCOFF-O and SCOFF-2.5 with EDE-Q werer = 0.53 andr = 0.56. The sensitivity and specificity of SCOFF-O were 65.2 and 89.7, and those of SCOFF-2.5 were 69.5 and 86.5, respectively. There were significant correlations between the question concerning losing 2.5 kg and the EDE-Q subscales. The Japanese version of SCOFF-2.5 is an appropriate tool for the early screening of eating disorders among Japanese university students.