bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional-level risk factors for severe hand-foot-and-mouth disease: an ecological study from mainland China
Authors: Pan Qing , Liu Fengfeng , Zhang Juying , Zhao Xing , Hu Yifan , Fan Chaonan , Yang Fan , Chang Zhaorui , Xiao Xiong
Published: January 2021

Background

Severe hand-foot-and-mouth disease (HFMD) is a life-threatening contagious disease among young children and infants. Although enterovirus A71 has been well acknowledged to be the dominant cause of severe HFMD, there still remain other unidentified risk factors for severe HFMD. Previous studies mainly focused on identifying the individual-level risk factors from a clinical perspective, while rare studies aimed to clarify the association between regional-level risk factors and severe HFMD, which may be more important from a public health perspective.

Methods

We retrieved the clinical HFMD counts between 2008 and 2014 from the Chinese Center for Disease Control and Prevention, which were used to calculated the case-severity rate in 143 prefectural-level cities in mainland China. For each of those 143 cities, we further obtained city-specific characteristics from the China City Statistical Yearbook (social and economic variables) and the national meteorological monitoring system (meteorological variables). A Poisson regression model was then used to estimate the associations between city-specific characteristics (reduced by the principal component analysis to avoid multicollinearity) and the case-severity rate of HFMD. The above analysis was further stratified by age and gender to examine potential modifying effects and vulnerable sub-populations.

Results

We found that the case-severity rate of HFMD varied dramatically between cities, ranging from 0 to 8.09%. Cities with high case-severity rates were mainly clustered in Central China. By relating the case-severity rate to city-specific characteristics, we found that both the principal component characterized by a high level of social and economic development (RR = 0.823, 95%CI 0.739, 0.916) and another that characterized by warm and humid climate (RR = 0.771, 95%CI 0.619, 0.960) were negatively associated with the case-severity rate of HFMD. These estimations were consistent across age and gender sub-populations.

Conclusion

Except for the type of infected pathogen, the case-severity rate of HFMD was closely related to city development and meteorological factor. These findings suggest that social and environmental factors may also play an important role in the progress of severe HFMD.
SARS-CoV-2 pneumonia succesfully treated with cpap and cycles of tripod position: a case report
Authors: Rauseo Michela , Mirabella Lucia , Caporusso Rosa Roberta , Cantatore Leonarda Pia , Perrini Marco Paolo , Vetuschi Paolo , La Bella Daniela , Tullo Livio , Cinnella Gilda
Published: January 2021

Background

Pneumonia induced by 2019 Coronavirus (COVID-19) is characterized by hypoxemic respiratory failure that may present with a broad spectrum of clinical phenotypes. At the beginning, patients may have normal lung compliance and be responsive to noninvasive ventilatory support, such as CPAP. However, the transition to more severe respiratory failure - Severe Acute Respiratory Syndrome (SARS-CoV-2), necessitating invasive ventilation is often abrupt and characterized by a severe V/Q mismatch that require cycles of prone positioning. The aim of this case is to report the effect on gas exchange, respiratory mechanics and hemodynamics of tripod (or orthopneic sitting position) used as an alternative to prone position in a patient with mild SARS-CoV-2 pneumonia ventilated with helmet CPAP.

Case presentation

A 77-year-old awake and collaborating male patient with mild SARS-CoV-2 pneumonia and ventilated with Helmet CPAP, showed sudden worsening of gas exchange without dyspnea. After an unsuccessful attempt of prone positioning, we alternated three-hours cycles of semi-recumbent and tripod position, still keeping him in CPAP. Arterial blood gases (PaO2/FiO2, PaO2, SaO2, PaCO2 and A/a gradient), respiratory (VE, VT, RR) and hemodynamic parameters (HR, MAP) were collected in the supine and tripod position. Cycles of tripod position were continued for 3 days. The patient had a clinically important improvement in arterial blood gases and respiratory parameters, with stable hemodynamic and was successfully weaned and discharged to ward 10 days after pneumonia onset.

Conclusions

Tripod position during Helmet CPAP can be applied safely in patients with mild SARS-CoV-2 pneumonia, with improvement of oxygenation and V/Q matching, thus reducing the need for intubation.
The impact of topical lidocaine and timing of LMA removal on the incidence of airway events during the recovery period in children: a randomized controlled trial
Authors: Sun Ruiqiang , Bao Xiaoyun , Gao Xuesong , Li Tong , Wang Quan , Li Yueping
Published: January 2021

Background

The timing of laryngeal mask airway (LMA) removal remains undefined. This study aimed to assess the optimal timing for LMA removal and whether topical anesthesia with lidocaine could reduce airway adverse events.

Methods

This randomized controlled trial assessed one-to-six-year-old children with ASA I-II scheduled for squint correction surgery under general anesthesia. The children were randomized into the LA (lidocaine cream smeared to the cuff of the LMA before insertion, with mask removal in the awake state), LD (lidocaine application and LMA removal under deep anesthesia), NLA (hydrosoluble lubricant application and LMA removal in the awake state) and NLD (hydrosoluble lubricant application and LMA removal in deep anesthesia) groups. The primary endpoint was a composite of irritating cough, laryngeal spasm, SpO2 < 96%, and glossocoma in the recovery period in the PACU. The secondary endpoints included the incidence of pharyngalgia and hoarseness within 24 h after the operation, duration of PACU stay, and incidence of agitation in the recovery period. The assessor was unblinded.

Results

Each group included 98 children. The overall incidence of adverse airway events was significantly lower in the LA group (9.4%) compared with the LD (23.7%), NLA (32.6%), and NLD (28.7%) groups (P=0.001). Cough and laryngeal spasm rates were significantly higher in the NLA group (20.0 and 9.5%, respectively) than the LA (5.2 and 0%, respectively), LD (4.1 and 1.0%, respectively), and NLD (9.6 and 2.1%, respectively) groups (P=0.001). Glossocoma incidence was significantly lower in the LA and NLA groups (0%) than in the LD (19.6%) and NLD (20.2%) groups (P< 0.001). At 24 h post-operation, pharyngalgia incidence was significantly higher in the NLA group (15.8%) than the LA (3.1%), LD (1.0%), and NLD (3.2%) groups (P< 0.001).

Conclusions

LMA removal in the awake state after topical lidocaine anesthesia reduces the incidence of postoperative airway events.

Trial registration

ChiCTR, ChiCTR-IPR-17012347. Registered August 12, 2017.
Psychological reactions and insomnia in adults with mental health disorders during the COVID-19 outbreak
Authors: Sun Qimeng , Qin Qingsong , Basta Maria , Chen Baixin , Li Yun
Published: January 2021

Background

The 2019 coronavirus disease (COVID-19) has disrupted millions of lives and commerce. We investigated psychological reactions and insomnia during the COVID-19 outbreak in adults with mental health disorders (MDs).

Methods

A self-reported psychological and sleep online survey was conducted in China between February 5th to 19th, 2020. A total of 244 adults with MDs and 1116 controls matched for age, gender and sites were included. Worsened symptoms of anxiety, depressive and insomnia were defined when severity levels shifted to a more severe category compared to pre-COVID-19.

Results

During the COVID-19 outbreak, we found significantly increased prevalence of anxiety (MDs: 54.9% vs. 49.6%, controls: 25.5% vs. 14.3%), depression (MDs: 63.9% vs. 61.5%, controls: 29.9% vs. 21.2%) and insomnia (MDs: 66.0% vs. 57.8%, controls: 31.5% vs. 24.8%) compared to pre-COVID-19 period (all P-value < 0.001). Furthermore, adults with MDs had higher odds for developing COVID-19-related stress (OR = 3.41, 95% CI 2.49 ~ 4.67), worsened anxiety (OR = 1.95, 95% CI 1.38 ~ 2.76), depression (OR = 2.04, 95% CI 1.43 ~ 2.93) and insomnia (OR = 2.22, 95% CI 1.53 ~ 3.21) during the COVID-19 outbreak compared to controls. Moreover, higher COVID-19-related stress and lower levels of pre-COVID-19 anxiety, depressive and insomnia symptoms were predictors for worsened anxiety, depression and insomnia in adults with MDs, respectively.

Conclusions

Our findings suggest that adverse psychological reactions and insomnia are more pronounced in adults with mental health disorders during the COVID-19 outbreak, thus more attention need to be provided.
Hyperalgesia affects muscle activity and knee range of motion during a single-limb mini squat in individuals with knee osteoarthritis: a cross-sectional study
Authors: Jorge Jéssica Garcia , Cabral Ana Luiza Costa e Silva , Moreira Vanessa Martins Pereira Silva , Hattori Wallisen Tadashi , Dionisio Valdeci Carlos
Published: January 2021

Background

The effect of hyperalgesia on functionality remains uncertain for individuals with knee osteoarthritis (KOA). This study aimed examine the clinical measures and hyperalgesia’s effect on muscle activity, knee range of motion (ROM) and postural control during the single-leg mini squat (SLMS) in individuals with KOA, determining the correlation between variables.

Methods

In this cross-sectional study, 60 individuals, 30 healthy (HG, 57.4 ± 6.86 years), and 30 with mild to moderate KOA (KOAG, 59.4 ± 5.46 years) were evaluated by the visual analog scale (VAS), Western Ontario and McMaster Universities Index (WOMAC), and the pressure pain threshold (PPT) in subcutaneous, myotomal, and sclerotomal structures. Muscle activity, knee ROM and postural control were assessed during a SLMS. The analyses were performed in the two phases of the SLMS. Phase 1 - during descending movement (eccentric contraction), Phase 2 - during ascending movement (concentric contraction). Analysis of covariance was applied for each variable separately, using weight as a co-variable. We used Spearman’s test for determining the correlation.

Results

There was no difference between groups for age, height, and postural control (p > 0.059), but KOAG presented the highest values for VAS and WOMAC (p = 0.000). In addition, EMG activity was higher in KOAG for gastrocnemius medialis and tibialis anterior muscles during phase 1 (p < 0.027), and for gastrocnemius medialis and gluteus medius muscles during phase 2 (p < 0.007), and reduced values for PPT and knee ROM (p = 0.000). Also, the correlations between PPT with muscle activity and postural control were moderate (rho< 0.482), while strong relationships were observed between some PPT points with VAS and WOMAC (rho> 0.507).

Conclusion

Hyperalgesia affects the functionality during a single-limb mini squat. There is an important correlation between hyperalgesia and muscle activity, postural control, and clinical measures in individuals with KOA.
Screening and referral is not enough: a qualitative exploration of barriers to access and uptake of mental health services in patients with cardiovascular diseases
Authors: Collopy C. M. , Cosh S. M. , Tully P. J.
Published: January 2021

Background

Cardiovascular diseases (CVD) are commonly comorbid with mental health disorders, portending poorer cardiac prognosis. Despite the high prevalence of depression and anxiety, and guidelines recommending routine depression screening and referral, uptake of mental healthcare in CVD populations remains low. Reasons for the underutilisation of mental health and psychological services for this population remain largely unknown.

Methods

Thirteen CVD patients with clinically significant psychological symptoms (depression, anxiety and/or stress) participated in one-on-one in-depth semi-structured interviews. Data were analysed using inductive thematic analysis.

Results

Barriers to uptake included the timing of referral and screening, with patients reporting a need for longer term follow-up. A lack of information provision and understanding around mental health and services, especially following cardiac-events were further barriers. A reluctance to report mental health or engage in services was also identified, with patients indicating a preference for informal peer support networks. A range of practical barriers such as mobility, transport and cost were also reported.

Conclusions

Longer term follow-up and routine mental health assessment may be beneficial to facilitate use of mental health services. Upskilling of practitioners around mental health may be a further avenue to promote information provision and enhance service use. Further focus on enhancing informal peer support may be a valuable initial approach for the CVD population. The implications for improving services and enhancing service use are discussed.
Mono-institutional retrospective cohort analysis of the insurance status dependent access to ENT-professionals and survival in head and neck squamous cell carcinoma
Authors: Knopf Andreas , Teutsch Simon , Bier Henning
Published: January 2021

Background

To access the influence of insurance status on time of diagnosis, quality of treatment and survival in head and neck squamous cell carcinoma (HNSCC).

Methods

This mono-institutional retrospective cohort analysis included all HNSCC patients (n = 1,054) treated between 2001 and 2011, and subdivided the cohort according to the insurance status. Differences between the groups were analyzed using the Chi square and the unpaired student’s t-test. Survival rates were calculated by Kaplan-Meier and Cox regression for forward selection.

Results

Nine hundred twenty-five patients showed general, 129 private insurance. The 2 groups were equal regarding age, gender, tumor localization, therapy, and N/M/G/R-status. The T-status differed significantly between the groups showing more advanced tumors in patients with general insurance (p = 0.002). While recurrence-free survival was comparable in both groups, overall survival was significantly better in private patients (p = 0.009). The time frame between first symptom and diagnosis was equal in both groups.

Conclusions

The time frame between subjective percipience of first symptom and final therapy did not differ between the groups. In our cohort, access to otorhinolaryngological specialists is favorable in both, patients with general and private insurance. Recurrence-free survival was comparable in both groups, indicating successful HNSCC treatment both groups. However, overall survival was significantly better in patients with private insurance suggesting other socioeconomic factors influencing survival.
Meta-ethnography in healthcare research: a guide to using a meta-ethnographic approach for literature synthesis
Authors: Sattar Raabia , Lawton Rebecca , Panagioti Maria , Johnson Judith
Published: January 2021

Background

Qualitative synthesis approaches are increasingly used in healthcare research. One of the most commonly utilised approaches is meta-ethnography. This is a systematic approach which synthesises data from multiple studies to enable new insights into patients’ and healthcare professionals’ experiences and perspectives. Meta-ethnographies can provide important theoretical and conceptual contributions and generate evidence for healthcare practice and policy. However, there is currently a lack of clarity and guidance surrounding the data synthesis stages and process.

Method

This paper aimed to outline a step-by-step method for conducting a meta-ethnography with illustrative examples.

Results

A practical step-by-step guide for conducting meta-ethnography based on the original seven steps as developed by Noblit & Hare (Meta-ethnography: Synthesizing qualitative studies.,1998) is presented. The stages include getting started, deciding what is relevant to the initial interest, reading the studies, determining how the studies are related, translating the studies into one another, synthesising the translations and expressing the synthesis.

We have incorporated adaptations and developments from recent publications. Annotations based on a previous meta-ethnography are provided. These are particularly detailed for stages 4–6, as these are often described as being the most challenging to conduct, but with the most limited amount of guidance available.

Conclusion

Meta-ethnographic synthesis is an important and increasingly used tool in healthcare research, which can be used to inform policy and practice. The guide presented clarifies how the stages and processes involved in conducting a meta-synthesis can be operationalised.
Development of a predictive model for integrated medical and long-term care resource consumption based on health behaviour: application of healthcare big data of patients with circulatory diseases
Authors: Takura Tomoyuki , Hirano Goto Keiko , Honda Asao
Published: January 2021

Background

Medical costs and the burden associated with cardiovascular disease are on the rise. Therefore, to improve the overall economy and quality assessment of the healthcare system, we developed a predictive model of integrated healthcare resource consumption (Adherence Score for Healthcare Resource Outcome, ASHRO) that incorporates patient health behaviours, and examined its association with clinical outcomes.

Methods

This study used information from a large-scale database on health insurance claims, long-term care insurance, and health check-ups. Participants comprised patients who received inpatient medical care for diseases of the circulatory system (ICD-10 codes I00-I99). The predictive model used broadly defined composite adherence as the explanatory variable and medical and long-term care costs as the objective variable. Predictive models used random forest learning (AI: artificial intelligence) to adjust for predictors, and multiple regression analysis to construct ASHRO scores. The ability of discrimination and calibration of the prediction model were evaluated using the area under the curve and the Hosmer-Lemeshow test. We compared the overall mortality of the two ASHRO 50% cut-off groups adjusted for clinical risk factors by propensity score matching over a 48-month follow-up period.

Results

Overall, 48,456 patients were discharged from the hospital with cardiovascular disease (mean age, 68.3 ± 9.9 years; male, 61.9%). The broad adherence score classification, adjusted as an index of the predictive model by machine learning, was an index of eight: secondary prevention, rehabilitation intensity, guidance, proportion of days covered, overlapping outpatient visits/clinical laboratory and physiological tests, medical attendance, and generic drug rate. Multiple regression analysis showed an overall coefficient of determination of 0.313 (p < 0.001). Logistic regression analysis with cut-off values of 50% and 25%/75% for medical and long-term care costs showed that the overall coefficient of determination was statistically significant (p < 0.001). The score of ASHRO was associated with the incidence of all deaths between the two 50% cut-off groups (2% vs. 7%; p < 0.001).

Conclusions

ASHRO accurately predicted future integrated healthcare resource consumption and was associated with clinical outcomes. It can be a valuable tool for evaluating the economic usefulness of individual adherence behaviours and optimising clinical outcomes.
Advances in sepsis diagnosis and management: a paradigm shift towards nanotechnology
Authors: Pant Amit , Mackraj Irene , Govender Thirumala
Published: January 2021

Sepsis, a dysregulated immune response due to life-threatening organ dysfunction, caused by drug-resistant pathogens, is a major global health threat contributing to high disease burden. Clinical outcomes in sepsis depend on timely diagnosis and appropriate early therapeutic intervention. There is a growing interest in the evaluation of nanotechnology-based solutions for sepsis management due to the inherent and unique properties of these nano-sized systems. This review presents recent advancements in nanotechnology-based solutions for sepsis diagnosis and management. Development of nanosensors based on electrochemical, immunological or magnetic principals provide highly sensitive, selective and rapid detection of sepsis biomarkers such as procalcitonin and C-reactive protein and are reviewed extensively. Nanoparticle-based drug delivery of antibiotics in sepsis models have shown promising results in combating drug resistance. Surface functionalization with antimicrobial peptides further enhances efficacy by targeting pathogens or specific microenvironments. Various strategies in nanoformulations have demonstrated the ability to deliver antibiotics and anti-inflammatory agents, simultaneously, have been reviewed. The critical role of nanoformulations of other adjuvant therapies including antioxidant, antitoxins and extracorporeal blood purification in sepsis management are also highlighted. Nanodiagnostics and nanotherapeutics in sepsis have enormous potential and provide new perspectives in sepsis management, supported by promising future biomedical applications included in the review.
Translation and validation of the Traditional Chinese version of the COmprehensive Score for financial Toxicity-Functional Assessment of Chronic Illness Therapy (Version 2)
Authors: Chan Dorothy N. S. , Choi Kai Chow , Ng Marques S. N. , Xing Weijie , Law Bernard M. H. , Ho Pui Shan , Au Cecilia , Chan Mandy , Tong Man , Ling Wai Man , Chan Maggie , Mak Suzanne S. S. , Chan Raymond J. , So Winnie K. W.
Published: January 2021

Background

Cancer patients often experience severe financial distress due to the high cost of their treatment, and strategies are needed to objectively measure this financial distress. The COmprehensive Score for financial Toxicity-Functional Assessment of Chronic Illness Therapy (COST-FACIT) is one instrument used to measure such financial distress. This study aimed to translate the COST-FACIT (Version 2) [COST-FACIT-v2] instrument into traditional Chinese (COST-FACIT-v2 [TC]) and evaluate its psychometric properties.

Methods

The Functional Assessment of Chronic Illness Therapy (FACIT) translation method was adopted. The translated version was reviewed by an expert panel and by 20 cancer patients for content validity and face validity, respectively, and 640 cancer patients, recruited from three oncology departments, completed the translated scale. Its reliability was evaluated in terms of internal consistency and test–retest reliability. Confirmatory factor analysis has been used to evaluate the one- and two-factor structures of the instrument reported in the literature. The convergent validity was examined by the correlation with health-related quality of life (HRQoL) and psychological distress. Known-group validity was examined by the difference in the COST-FACIT-v2 (TC) total mean score between groups with different income levels and frequency of health care service use.

Results

The COST-FACIT-v2 (TC) showed good content and face validity and demonstrated high internal consistency (Cronbach’s alpha, 0.86) and acceptable test–retest reliability (intraclass correlation coefficient, 0.71). Confirmatory factor analysis showed that the one- and two-factor structures of the instrument that have been reported in the literature could not be satisfactorily fitted to the data. Psychological distress correlated significantly with the COST-FACIT-v2 (TC) score (r = 0.47; p < 0.001). HRQOL showed a weak to moderate negative correlation with the COST-FACIT-v2 (TC) score (r = − 0.23 to − 0.46; p < 0.001). Significant differences were seen among the COST-FACIT-v2 (TC) scores obtained in groups of different income level and frequency of health care service use.

Conclusions

The COST-FACIT-v2 (TC) showed some desirable psychometric properties to support its validity and reliability for assessing cancer patients’ level of financial toxicity.
Hypoxia and its possible relationship with endometrial receptivity in adenomyosis: a preliminary study
Authors: Guo Song , Zhang Di , Lu Xiaowei , Zhang Qian , Gu Ruihuan , Sun Binghui , Sun Yijuan
Published: January 2021

Background

Adenomyosis (AM) is an important cause of female infertility. However, the underlying mechanism remains unclear. This report describes a preliminary study of hypoxia and its possible association with endometrial receptivity in AM.

Methods

The study was divided into in vitro and in vivo experiments. In vitro, expression levels of the endometrial receptivity markers HOXA10 and HOXA11 in the implantation period were examined using real-time PCR and western blotting. Endometrial expression of hypoxia-inducible factor (HIF)-1α, HIF-2α, and HIF-3α was determined using immunohistochemistry. In vivo, using an AM mouse model established by oral administration of tamoxifen, we inhibited expression of HIF-2α using an HIF-2α antagonist (PT2399; 30 mg/kg body weight, twice daily by oral gavage for 2 days) and then examined expression levels of Hoxa10 and Hoxa11 using real-time PCR and western blotting.

Results

Endometrial mRNA and protein expression levels of HOXA10 and HOXA11 were significantly lower in patients with AM than in control patients. Expression of HIF-2α was significantly higher in the AM group than in the control group, whereas that of HIF-1α and HIF-3α was equivalent in both groups. In vivo analysis showed that administration of the HIF-2α antagonist resulted in increased expression of Hoxa10 and Hoxa11 at both the mRNA and protein levels in AM model mice.

Conclusions

HIF-2α overexpression may be one reason for decreased endometrial receptivity in AM. The current findings provide insight into HIF-2α-mediated AM-related infertility and suggest that PT2399 has potential as a treatment for AM.

Trial registration

This trial was retrospectively registered.
Effects of spinal manipulative therapy on inflammatory mediators in patients with non-specific low back pain: a non-randomized controlled clinical trial
Authors: Teodorczyk-Injeyan Julita A. , Triano John J. , Gringmuth Robert , DeGraauw Christopher , Chow Adrian , Injeyan H. Stephen
Published: January 2021

Background

The inflammatory profiles of patients with acute and chronic nonspecific low back pain (LBP) patients are distinct. Spinal manipulative therapy (SMT) has been shown to modulate the production of nociceptive chemokines differently in these patient cohorts. The present study further investigates the effect(s) of SMT on other inflammatory mediators in the same LBP patient cohorts.

Methods

Acute (n = 22) and chronic (n = 25) LBP patients with minimum pain scores of 3 on a 10-point numeric scale, and asymptomatic controls (n = 24) were recruited according to stringent exclusion criteria. Blood samples were obtained at baseline and after 2 weeks during which patients received 6 SMTs in the lumbar or lumbosacral region. The in vitro production of tumor necrosis factor (TNFα), interleukin-1 β (IL-1β), IL-6, IL-2, interferon ɣ (IFNɣ), IL-1 receptor antagonist (IL-1RA), TNF soluble receptor type 2 (sTNFR2) and IL-10 was determined by specific immunoassays. Parametric as well as non-parametric statistics (PAST 3.18 beta software) was used to determine significance of differences between and within study groups prior and post-SMT. Effect size (ES) estimates were obtained using Cohen’sd.

Results

Compared with asymptomatic controls, SMT-related change scores were significant (P = 0.03–0.01) in reducing the production levels of TNFα in both patient cohorts and those of IL-6, IFNɣ and sTNFR2 (P = 0.001–0.02) in patients with chronic LBP. Above-moderate to large ES (d > 0.6–1.4) was observed for these mediators. Compared with respective baselines, a significant post-SMT reduction (P = 0.01) of IL-6 production was detected only in patients with chronic LBP while a significant increase of IL-2 production (P = 0.001 vs. control, andP = 0.004 vs. chronic LBP group) and a large ES (d = 0.87) were observed in patients with acute LBP. Pain and disability scores declined significantly (P < 0.001) in all LBP patients, and were positively correlated (P = 0.03) with IFNɣ and IL-2 levels in the acute LBP cohort.

Conclusion

The short course of SMT treatments of non-specific LBP patients resulted in significant albeit limited and diverse alterations in the production of several of the mediators investigated in this study. This exploratory study highlights the potential of SMT to modulate the production of inflammatory components in acute and chronic non-specific LBP patients and suggests a need for further, randomized controlled clinical trials in this area.

Trial registration

This study was prospectively registered April 2012 with Clinical Trials.gov (#NCT01766141).

https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0003ZIL&selectaction=Edit&uid=U0001V74&ts=2&cx=-axvqtg
miR-145 inhibits mitochondrial function of ovarian cancer by targeting ARL5B
Authors: Zhao Shuo , Zhang Yun , Pei Meili , Wu Lei , Li Jie
Published: January 2021

Metabolic reprogramming refers to the transformation of the whole metabolic network including glycolysis and mitochondrial metabolism, mainly manifested in Warburg effect and mitochondrial metabolic reprogramming. The roles of miR-145 in glycolysis have been established in ovarian cancer cells. Howerer, its roles in mitochondrial metabolic reprogramming are still unclear. This study aims to identify whether miR-145 regulates mitochondrial metabolic reprogramming in ovarian cancer cells. First, functional experiment showed that overexpression of miR-145 inhibited mitochondrial function in ovarian cancer cells, evident by the decreased mtDNA copy numbers, ATP level, mitochondrial membrane potential, and the expression levels of mitochondrial markers. Mechanistically, miR-145 inhibited mitochondrial function by targeting ARL5B directly. Futhermore, miR-145 overexpression decreased ARL5B expression in ovarian cancer tissue subcutaneous tumors of nude mice. In conclusion, we have highlighted that miR-145 inhibits mitochondrial function and achieves this by targeting ARL5B directly for the first time. The results provides a more adequate theoretical basis for understanding the molecular pathology of ovarian cancer, and provides the necessary basic data for miR-145 as a potential diagnosis and treatment target for ovarian cancer.
Evolution of regulatory networks associated with traits under selection in cichlids
Authors: Mehta Tarang K. , Koch Christopher , Nash Will , Knaack Sara A. , Sudhakar Padhmanand , Olbei Marton , Bastkowski Sarah , Penso-Dolfin Luca , Korcsmaros Tamas , Haerty Wilfried , Roy Sushmita , Di-Palma Federica
Published: January 2021

Background

Seminal studies of vertebrate protein evolution speculated that gene regulatory changes can drive anatomical innovations. However, very little is known about gene regulatory network (GRN) evolution associated with phenotypic effect across ecologically diverse species. Here we use a novel approach for comparative GRN analysis in vertebrate species to study GRN evolution in representative species of the most striking examples of adaptive radiations, the East African cichlids. We previously demonstrated how the explosive phenotypic diversification of East African cichlids can be attributed to diverse molecular mechanisms, including accelerated regulatory sequence evolution and gene expression divergence.

Results

To investigate these mechanisms across species at a genome-wide scale, we develop a novel computational pipeline that predicts regulators for co-extant and ancestral co-expression modules along a phylogeny, and candidate regulatory regions associated with traits under selection in cichlids. As a case study, we apply our approach to a well-studied adaptive trait—the visual system—for which we report striking cases of network rewiring for visual opsin genes, identify discrete regulatory variants, and investigate their association with cichlid visual system evolution. In regulatory regions of visual opsin genes, in vitro assays confirm that transcription factor binding site mutations disrupt regulatory edges across species and segregate according to lake species phylogeny and ecology, suggesting GRN rewiring in radiating cichlids.

Conclusions

Our approach reveals numerous novel potential candidate regulators and regulatory regions across cichlid genomes, including some novel and some previously reported associations to known adaptive evolutionary traits.
Homology-mediated inter-chromosomal interactions in hexaploid wheat lead to specific subgenome territories following polyploidization and introgression
Authors: Jia Jizeng , Xie Yilin , Cheng Jingfei , Kong Chuizheng , Wang Meiyue , Gao Lifeng , Zhao Fei , Guo Jingyu , Wang Kai , Li Guangwei , Cui Dangqun , Hu Tiezhu , Zhao Guangyao , Wang Daowen , Ru Zhengang , Zhang Yijing
Published: January 2021

Background

Polyploidization and introgression are major events driving plant genome evolution and influencing crop breeding. However, the mechanisms underlying the higher-order chromatin organization of subgenomes and alien chromosomes are largely unknown.

Results

We probe the three-dimensional chromatin architecture of Aikang 58 (AK58), a widely cultivated allohexaploid wheat variety in China carrying the 1RS/1BL translocation chromosome. The regions involved in inter-chromosomal interactions, both within and between subgenomes, have highly similar sequences. Subgenome-specific territories tend to be connected by subgenome-dominant homologous transposable elements (TEs). The alien 1RS chromosomal arm, which was introgressed from rye and differs from its wheat counterpart, has relatively few inter-chromosome interactions with wheat chromosomes. An analysis of local chromatin structures reveals topologically associating domain (TAD)-like regions covering 52% of the AK58 genome, the boundaries of which are enriched with active genes, zinc-finger factor-binding motifs, CHH methylation, and 24-nt small RNAs. The chromatin loops are mostly localized around TAD boundaries, and the number of gene loops is positively associated with gene activity.

Conclusions

The present study reveals the impact of the genetic sequence context on the higher-order chromatin structure and subgenome stability in hexaploid wheat. Specifically, we characterized the sequence homology-mediated inter-chromosome interactions and the non-canonical role of subgenome-biased TEs. Our findings may have profound implications for future investigations of the interplay between genetic sequences and higher-order structures and their consequences on polyploid genome evolution and introgression-based breeding of crop plants.
Evaluation of robotic versus open partial pancreatoduodenectomy—study protocol for a randomised controlled pilot trial (EUROPA, DRKS00020407)
Authors: Klotz Rosa , Dörr-Harim Colette , Bruckner Thomas , Knebel Philipp , Diener Markus K. , Hackert Thilo , Mihaljevic André L.
Published: January 2021

Background

Partial pancreatoduodenectomy (PD) is the indicated surgical procedure for a wide range of benign and malignant diseases of the pancreatic head and distal bile duct and offers the only potential cure for pancreatic head cancer. The current gold standard, open PD (OPD) performed via laparotomy, is associated with morbidity in around 40% of cases, even at specialised centres. Robotic PD (RPD) might offer a viable alternative to OPD and has been shown to be feasible. Encouraging perioperative results have been reported for RPD in a number of small, non-randomised studies. However, since those studies showed a considerable risk of bias, a thorough comparison of RPD with OPD is warranted.

Methods

The EUROPA (EvalUation of RObotic partial PAncreatoduodenectomy) trial is designed as a randomised controlled unblinded exploratory surgical trial with two parallel study groups. A total of 80 patients scheduled for elective PD will be randomised after giving written informed consent. Patients with borderline or non-resectable carcinoma of the pancreatic head as defined by the National Comprehensive Cancer Network guidelines, distant metastases or an American Society of Anaesthesiologists (ASA) score > III will be excluded. The experimental intervention, RPD, will be compared with the control intervention, OPD. An intraoperative dropout of approximately eight patients per group is expected because they may receive another type of surgical procedure than planned. Overall, 64 patients need to be analysed. The primary endpoint of the trial is overall postoperative morbidity within 90 days after index operation, measured using the Comprehensive Complication Index (CCI). The secondary endpoints include the feasibility of recruitment and assessment of clinical, oncological and safety parameters and quality of life and cost-effectiveness.

Discussion

The EUROPA trial is the first randomised controlled trial comparing RPD with OPD. Differences in postoperative morbidity will be evaluated to design a future multicentre confirmatory efficacy trial.

Trial registration

German Clinical Trial Register DRKS00020407. Registered on 9 March 2020
Process optimization for mass production of 2,3-butanediol by Bacillus subtilis CS13
Authors: Wang Dexin , Oh Baek-Rock , Lee Sungbeom , Kim Dae-Hyuk , Joe Min-Ho
Published: January 2021

Background

Bacillus subtilis CS13 was previously isolated for 2,3-butanediol (2,3-BD) and poly-γ-glutamic acid (γ-PGA) co-production. When culturing this strain without L-glutamic acid in the medium, 2,3-BD is the main metabolic product. 2,3-BD is an important substance and fuel with applications in the chemical, food, and pharmaceutical industries. However, the yield and productivity for the B. subtilis strain should be improved for more efficient production of 2,3-BD.

Results

The medium composition, which contained 281.1 g/L sucrose, 21.9 g/L ammonium citrate, and 3.6 g/L MgSO4·7H2O, was optimized by response surface methodology for 2,3-BD production using B. subtilis CS13. The maximum amount of 2,3-BD (125.5 ± 3.1 g/L) was obtained from the optimized medium after 96 h. The highest concentration and productivity of 2,3-BD were achieved simultaneously at an agitation speed of 500 rpm and aeration rate of 2 L/min in the batch cultures. A total of 132.4 ± 4.4 g/L 2,3-BD was obtained with a productivity of 2.45 ± 0.08 g/L/h and yield of 0.45 g2,3-BD/gsucrose by fed-batch fermentation. The meso-2,3-BD/2,3-BD ratio of the 2,3-BD produced by B. subtilis CS13 was 92.1%. Furthermore, 89.6 ± 2.8 g/L 2,3-BD with a productivity of 2.13 ± 0.07 g/L/h and yield of 0.42 g2,3-BD/gsugar was achieved using molasses as a carbon source.

Conclusions

The production of 2,3-BD by B. subtilis CS13 showed a higher concentration, productivity, and yield compared to the reported generally recognized as safe 2,3-BD producers. These results suggest that B. subtilis CS13 is a promising strain for industrial-scale production of 2,3-BD.
Familial chylomicronemia syndrome: a case report
Authors: Susheela Ammu Thampi , Vadakapet Padmesh , Pillai Lekshmi , Thampi Susheela
Published: January 2021

Background

Familial chylomicronemia is an extremely rare disease. Lipoprotein lipase deficiency, lipoprotein defect or lipoprotein receptor defect are the main genetic causes of familial chylomicronemia.

Case presentation

We report a rare case of hypertriglyceridemia which was diagnosed at 24 days after birth. A newborn south east Asian baby born for G3P2A1 mother was presented with hematuria at 24 days at the hospital. The patient's family history is significant for pink blood in an elder sibling who died within a few months of birth without a proper diagnosis. Physical examination was not significant for any findings. Urinalysis revealed numerous RBC in the urine. Blood draw to perform renal function test revealed a characteristic pink blood. Baby’s blood was normal and red in color at the time of birth. During the present visit, although most of the blood test were not able to be carried out by the regular laboratory instruments, the patient’s lipid profile was alarmingly high with triglyceride levels over 4000 mg/dL. Due to a very high triglyceride level in a neonate and a significant familial history, a genetic cause of hypertriglyceridemia is suspected. Upon diagnosis, baby was discontinued of breast feeding completely and was given a special diet devoid of triglyceride and containing medium chain fatty acid diet and was also started with fenofibrate. After a month and a half, follow up tests were conducted which showed the triglyceride level was reduced to 1300 and a reversal of the blood color from pink to red. Since the imported diet was extremely expensive for the family, the patient was put on skimmed milk with medium-chain triglyceride (MCT) oil. With 6 weeks of treatment, baby’s condition has improved and is thriving well.

Conclusions

Our case reports an extremely rare and fatal condition and illustrated the significance of timely diagnosis and intervention for saving the life of the baby.
The impact of savings on economic growth in a developing country (the case of Kosovo)
Authors: Ribaj Artur , Mexhuani Fitim
Published: January 2021

The correlation between savings and economic growth has been the subject of research for some well-known economists. This study provides further insight on such correlation by examining the case of Kosovo from both a qualitative and quantitative research methodology. The data used was from 2010 to 2017 and has been analyzed using the augmented Dickey-Fuller tests, Johansen cointegration tests, and Ganger causality test. The test of the unit root confirms stationarity, and the regression results showed that deposits have a significant positive impact on Kosovo’s economic growth, because savings stimulate investment, production, and employment and consequently generate greater sustainable economic growth. Furthermore, loans and remittances also help boost the economy of Kosovo through their direct impact on investment. This paper confirms that countries whose national savings rate is high are not dependent on foreign direct investment; consequently, the risk arising from volatile foreign direct investment decreases significantly.
Bilateral severe heterotopic ossification following primary total knee arthroplasty: a case report in Pakistan
Authors: Iqbal Faizan , Memon Nouman , Noor Syed Shahid , Ahmed Nasir , Sozera Muhammad Farhan , Abro Arsalan
Published: January 2021

The incidence of unilateral minor heterotopic ossification after primary total knee arthroplasty is still unknown, but bilateral severe heterotopic ossification is rare and has not been reported before. Presented in this report is a 60-year-old female patient who developed bilateral knee pain and stiffness 2 weeks after primary total knee arthroplasty. Her weight was 70 kg and body mass index was 32.2. Preoperatively, she had bilateral varus deformity of both knees. X-rays taken 3 months after surgery revealed bilateral severe heterotopic ossification. The patient had been on non-operative treatment (including anti-inflammatory drugs and physiotherapy). There was a marked improvement 6 months after surgery. This case report showed the non-operative treatment may produce acceptable results for patients with severe bilateral heterotopic ossification after primary total knee arthroplasty, and exerted no influence on the final clinical outcome.
Risk-Adapted Preemptive Tocilizumab to Prevent Severe Cytokine Release Syndrome After CTL019 for Pediatric B-Cell Acute Lymphoblastic Leukemia: A Prospective Clinical Trial
Authors: Kadauke Stephan , Myers Regina M. , Li Yimei , Aplenc Richard , Baniewicz Diane , Barrett David M. , Barz Leahy Allison , Callahan Colleen , Dolan Joseph G. , Fitzgerald Julie C. , Gladney Whitney , Lacey Simon F. , Liu Hongyan , Maude Shannon L. , McGuire Regina , Motley Laura S. , Teachey David T. , Wertheim Gerald B. , Wray Lisa , DiNofia Amanda M. , Grupp Stephan A.
Published: January 2021

PURPOSE

To prospectively evaluate the effectiveness of risk-adapted preemptive tocilizumab (PT) administration in preventing severe cytokine release syndrome (CRS) after CTL019, a CD19 chimeric antigen receptor T-cell therapy.

METHODS

Children and young adults with CD19-positive relapsed or refractory B-cell acute lymphoblastic leukemia were assigned to high- (≥ 40%) or low- (< 40%) tumor burden cohorts (HTBC or LTBC) based on a bone marrow aspirate or biopsy before infusion. HTBC patients received a single dose of tocilizumab (8-12 mg/kg) after development of high, persistent fevers. LTBC patients received standard CRS management. The primary end point was the frequency of grade 4 CRS (Penn scale), with an observed rate of ≤ 5 of 15 patients in the HTBC pre-defined as clinically meaningful. In post hoc analyses, the HTBC was compared with a historical cohort of high-tumor burden patients from the initial phase I CTL019 trial.

RESULTS

The primary end point was met. Seventy patients were infused with CTL019, 15 in the HTBC and 55 in the LTBC. All HTBC patients received the PT intervention. The incidence of grade 4 CRS was 27% (95% CI, 8 to 55) in the HTBC and 3.6% (95% CI, 0.4 to 13) in the LTBC. The best overall response rate was 87% in the HTBC and 100% in the LTBC. Initial CTL019 expansion was greater in the HTBC than the LTBC ( P < .001), but persistence was not different ( P = .73). Event-free and overall survival were worse in the HTBC ( P = .004, P < .001, respectively). In the post hoc analysis, grade 4 CRS was observed in 27% versus 50% of patients in the PT and prior phase I cohorts, respectively ( P = .18).

CONCLUSION

Risk-adapted PT administration resulted in a decrease in the expected incidence of grade 4 CRS, meeting the study end point, without adversely impacting the antitumor efficacy or safety of CTL019.
Mobile Applications: Breaking Barriers to Early Breast and Cervical Cancer Detection in Underserved Communities
Authors: Munoz-Zuluaga Carlos A. , Gallo-Pérez José David , Pérez-Bustos Andrés , Orozco-Urdaneta Mavalynne , Druffel Karen , Cordoba-Astudillo Lida P. , Parra-Lara Luis G. , Velez-Mejia Carolina , El-sharkawy Farah , Zambrano-Vera Katherin , Erazo Raúl H. , King Mary C. , Sardi Armando
Published: January 2021

BACKGROUND:

Although potentially curable with early detection and timely treatment, breast cancer (BC) and cervical cancer (CC) remain leading causes of death for Colombian women. Lack of education, complicated administrative processes, and geographic limitations hinder early cancer detection. Today, technological tools permeate the society and could assess user risk, deliver customized information, and provide care coordination. We evaluated the effectiveness of a free mobile application (mApp) to reach women, understand misconceptions, identify users at risk for BC and/or CC, and coordinate screening tests in Cali, Colombia.

METHODS:

The mApp was developed and advertised in four healthcare facility waiting rooms. It used educational, evaluative, and risk factor questions followed by brief explanations to assess the population's knowledge, educate on BC and/or CC, and identify users in need of screening test(s). Women who required screening were navigated and enrolled in the national cancer program.

RESULTS:

From August 2017 to August 2019, 1,043 women downloaded the mApp. BC misconceptions included beliefs that BC can be prevented (87%), obesity does not increase the risk of BC (49%), and deodorant causes BC (17%). CC misconceptions included that pap smears should not be performed while sexually active (64%), vaginal pain is an early sign of CC (44%), and only women contract human papilloma virus (33%). Overall, 29% (303) were identified as at risk and needed a screening test, with 32% (98) successfully screened.

DISCUSSION:

mApps can identify women at risk for BC and/or CC, detect barriers to early cancer detection, and help coordinate screening test(s). This technology has widespread applications and may be useful in other underserved communities.