bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonlinear physics opens a new paradigm for accurate transcription start site prediction
Authors: Barbero-Aparicio José Antonio , Cuesta-Lopez Santiago , García-Osorio César Ignacio , Pérez-Rodríguez Javier , García-Pedrajas Nicolás
Published: December 2022

There is evidence that DNA breathing (spontaneous opening of the DNA strands) plays a relevant role in the interactions of DNA with other molecules, and in particular in the transcription process. Therefore, having physical models that can predict these openings is of interest. However, this source of information has not been used before either in transcription start sites (TSSs) or promoter prediction. In this article, one such model is used as an additional information source that, when used by a machine learning (ML) model, improves the results of current methods for the prediction of TSSs. In addition, we provide evidence on the validity of the physical model, as it is able by itself to predict TSSs with high accuracy. This opens an exciting avenue of research at the intersection of statistical mechanics and ML, where ML models in bioinformatics can be improved using physical models of DNA as feature extractors.
Integrative analysis of transcriptome and metabolism reveals potential roles of carbon fixation and photorespiratory metabolism in response to drought in Shanlan upland rice
Authors: Zhou Shubo , He Lijing , Lin Wei , Su Yi , Liu Qing , Qu Mingnan , Xiao Langtao
Published: December 2022

Shanlan upland rice is an important landrace rice resource and is characterized with high drought stress (DS) tolerance relative to cultivated rice. However, the molecular mechanism of DS response in Shanlan upland rice remains unclear. In this study, we performed an integrated analysis of transcriptome and targeted metabolism to decipher the key biological pathways that responded to drought tolerance using two Shanlan upland rice lines. Results show that SL10 possesses 64% higher photosynthetic efficiency (Pn) and 2-fold higher water use efficiency (WUE) than that in SL1 exposed to DS. The decrease in Pn by DS is not due to stomatal limitation effects for SL1. Transcriptome analysis suggests photosynthesis relevant pathways (photosynthesis-antenna proteins and carbon fixation) and photorespiration relevant pathway (glycine, serine and threonine metabolism) in SL1 under DS were significantly enriched in the down-regulated and up-regulated DEGs list, respectively. There are 412 up-regulated and 233 down-regulated drought responsive genes (DRGs) in SL10 relative to SL1 induced by DS. Targeted metabolism results suggest that the contents across five metabolites related to carbon fixation pathway were declined by 36 and 8% in SL1 and SL10 caused by DS, respectively. We finally summarized the both gene expression and metabolites involved in photorespiration and carbon fixation pathways in response to DS in both rice lines. This study provides valuable information for better understanding the molecular mechanism underlying drought tolerance in Shanlan rice.
Anesthesia and surgery-induced elevation of CSF sTREM2 is associated with early cognitive dysfunction after thoracoabdominal aortic dissection surgery
Authors: Wang Kexin , Cao Xuezhao , Li Zhe , Liu Sidan , Zhou Yongjian , Guo Lili , Li Pengli
Published: December 2022

Purpose

Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) concentration is increased in cerebrospinal fluid (CSF) in early symptomatic phase of Alzheimer’s disease (AD). This study investigated whether CSF sTREM2 has a relationship with early cognitive dysfunction following surgery in cardiac surgery patients.

Methods

A total of 82 patients undergoing thoracoabdominal aortic replacement were recruited in this study. Neuropsychological testing battery was conducted before and after surgery. Postoperative cognitive dysfunction (POCD) was defined as a Z-score > 1.96 on at least 2 different tests or Telephone Interviews for Cognitive Status-Modified (TICS-M) score < 27. The CSF and serum sTREM2, Aβ42, T-tau and P-tau were collected and measured by ELISA on day before surgery and postoperative day 3.

Results

Patients were classified into POCD (n = 34) and non-POCD (n = 48) groups according to Z-score. Compared to non-POCD group, the levels of CSF sTREM2 (p < 0.001) and serum sTREM2 (p = 0.001) were significantly higher in POCD group on postoperative day 3. The levels of Aβ42 (p = 0.005) and Aβ42/T-tau ratio (p = 0.036) were significantly lower in POCD group on postoperative day 3. Multivariate logistic regression analysis revealed that higher value of postoperative CSF sTREM2 (odds ratio: 1.06, 95% confidence interval: 1.02–1.11, p = 0.009), age (OR: 1.15, 95%CI: 1.03–1.28, p = 0.014) and POD duration (OR: 2.47, 95%CI: 1.15–5.29, p = 0.02) were the risk factors of POCD.

Conclusion

This study indicates that anesthesia and surgery-induced elevation of CSF sTREM2 is associated with an increased risk of early cognitive dysfunction following surgery.
Effect of facemask oxygenation with and without positive pressure ventilation on gastric volume during anesthesia induction in patients undergoing laparoscopic cholecystectomy or partial hepatectomy: a randomized controlled trial
Authors: He Guangting , Ma Liyun , Tian Ke , Cao Yuqi , Qin Zaisheng
Published: December 2022

Background

Studies focusing on the relationship between gastric volume and facemask oxygenation without ventilation during apnea in anesthesia induction are scarce. This study compared the change in gastric volume during apnea in anesthesia induction using facemask ventilation and facemask oxygenation without ventilation in adults undergoing laparoscopic surgery.

Methods

In this prospective, randomized, double-blinded trial, 70 adults undergoing laparoscopic surgery under general anesthesia were divided into two groups to receive facemask oxygenation with and without ventilation for 60 seconds after loss of consciousness. Before anesthesia induction and after endotracheal intubation, the gastric antral cross-sectional area was measured with ultrasound imaging. Arterial blood gases were tested at baseline (T1), after preoxygenation (T2), after loss of consciousness (T3), and before and after endotracheal intubation (T4 and T5, respectively).

Results

Sixty patients were included (ventilation n = 30; non ventilation n = 30, 10 patients were excluded). The median [IQR] change of gastric antral cross-sectional area in ventilation group was significantly higher than in non ventilation group (0.83 [0.20 to 1.54] vs. 0.10 [− 0.11 to 0.56] cm2, P = 0.001). At T4 and T5, the PaO2 in ventilation group was significantly higher than in non ventilation group (T4: 391.83 ± 61.53 vs. 336.23 ± 74.99 mmHg, P < 0.01; T5: 364.00 ± 58.65 vs. 297.13 ± 86.95 mmHg, P < 0.01), while the PaCO2 in non ventilation group was significantly higher (T4: 46.57 ± 5.78 vs. 37.27 ± 6.10 mmHg, P < 0.01; T5: 48.77 ± 6.59 vs. 42.63 ± 6.03 mmHg, P < 0.01) and the pH value in non ventilation group was significantly lower (T4: 7.35 ± 0.029 vs 7.42 ± 0.047, P < 0.01; T5: 7.34 ± 0.033 vs 7.39 ± 0.044, P < 0.01). At T4, the HCO3− in non ventilation group was significantly higher (25.79 ± 2.36 vs. 23.98 ± 2.18 mmol l− 1, P < 0.01).

Conclusions

During apnoea, the increase in gastric volume was milder in patients undergoing facemask oxygenation without ventilation than with positive pressure ventilation.

Trial registration

ChiCTR2100054193, 10/12/2021, Title: “Effect of positive pressure and non-positive pressure ventilation on gastric volume during induction of general anesthesia in laparoscopic surgery: a randomized controlled trial”. Website: https://www.chictr.ogr.cn.
Association of motor index scores with fall incidence among community-dwelling older people
Authors: Liu Xiao , Abudukeremu Ayiguli , Jiang Yuan , Cao Zhengyu , Wu Maoxiong , Zheng Kai , Ma Jianyong , Sun Runlu , Chen Zhiteng , Chen Yangxin , Zhang Yuling , Wang Jingfeng
Published: December 2022

Background

Several kinds of motor dysfunction have been studied for predicting future fall risk in community-dwelling older individuals. However, no study has tested the ability of the fine motor index (FINEA) and gross motor index (GROSSA) to predict the risk of falling, as well as the specific fall type.

Objective

We investigated the associations of FINEA/GROSSA scores with fall risk, explained falls, and unexplained falls.

Methods

A total of 6267 community-dwelling adults aged ≥ 50 years from the Irish Longitudinal Study on Aging (TILDA) cohort were included. First, the associations of FINEA and GROSSA scores with the history of total falls, explained falls and unexplained falls were assessed in a cross-sectional study and further verified in a prospective cohort after 2 years of follow-up by Poisson regression analysis.

Results

We found that high FINEA and GROSSA scores were positively associated with almost all fall histories (FINEA scores: total falls: adjusted prevalence ratio [aPR] = 1.28,P = 0.009; explained falls: aPR = 1.15,P = 0.231; unexplained falls: aPR = 1.88,P < 0.001; GROSSA scores: total falls: aPR = 1.39,P < 0.001; explained falls: aPR = 1.28,P = 0.012; unexplained falls: aPR = 2.18,P < 0.001) in a cross-sectional study. After 2 years of follow-up, high FINEA scores were associated with an increased incidence of total falls (adjusted rate ratio [aRR] = 1.42,P = 0.016) and explained falls (aRR = 1.51,P = 0.020) but not with unexplained falls (aRR = 1.41,P = 0.209). High GROSSA scores were associated with an increased incidence of unexplained falls (aRR = 1.57,P = 0.041) and were not associated with either total falls (aRR = 1.21,P = 0.129) or explained falls (aRR = 1.07,P = 0.656). Compared with individuals without limitations in either the FINEA or GROSSA, individuals with limitations in both indices had a higher risk of falls, including total falls (aRR = 1.35,P = 0.002), explained falls (aRR = 1.31,P = 0.033) and unexplained falls (aRR = 1.62,P = 0.004).

Conclusion

FINEA scores were positively associated with accidental falls, while GROSSA scores were positively associated with unexplained falls. The group for whom both measures were impaired showed a significantly higher risk of both explained and unexplained falls. FINEA or GROSSA scores should be investigated further as possible tools to screen for and identify community-dwelling adults at high risk of falling.
A new model of preoperative systemic inflammatory markers predicting overall survival of osteosarcoma: a multicenter retrospective study
Authors: Huang Xianying , Liu Yongjin , Liang Weifeng , Luo Kai , Qin Yiwu , Li Feicui , Xie Tianyu , Qin Haibiao , He Juliang , Wei Qingjun
Published: December 2022

Background

The purpose of this study was to investigate the significance of preoperative C-reactive protein-to-albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in predicting overall survival (OS) of osteosarcoma, to establish a nomogram of an individualized prognostic prediction model for osteosarcoma.

Methods

Two hundred thirty-five patients with osteosarcoma from multiple centers were included in this study. Receiver operating characteristic (ROC) and Youden index were used to determine the optimal cutoff values ​​for CAR, NLR, and PLR. Univariate analysis using COX proportional hazards model to identify factors associated with OS in osteosarcoma, and multivariate analysis of these factors to identify independent prognostic factors. R software (4.1.3-win) rms package was used to build a nomogram, and the concordance index (C-index) and calibration curve were used to assess model accuracy and discriminability.

Results

Univariate analysis revealed that the OS of osteosarcoma is significantly correlated (P < 0.05) with CAR, NLR, PLR, Enneking stage, tumor size, age, neoadjuvant chemotherapy (NACT), and high alkaline phosphatase. Multivariate analysis confirmed that CAR, NLR, Enneking stage, NACT and tumor size are independent prognostic factors for OS of osteosarcoma. The calibration curve shows that the nomogram constructed from these factors has acceptable consistency and calibration capability.

Conclusion

Preoperative CAR and NLR were independent predictors of osteosarcoma prognosis, and the combination of nomogram model can realize individualized prognosis prediction and guide medical practice.
Exploring challenges and mitigation strategies towards practicing Teledentistry
Authors: Fahim Ayesha , Saleem Zakia , Malik Khizar Ansar , Atta Komal , Mahmood Rizwan , Alam Mohammad Khursheed , Sethi Ahsan
Published: December 2022

Background

Since the beginning of the COVID-19 pandemic, many dentists have opted for Teledentistry as a mechanism for patient consultation, oral lesion evaluation, diagnosis, and monitoring. The current study explores the challenges faced and potential solutions proposed by dentists practicing Teledentistry in a developing country like Pakistan.

Methods

A qualitative case study was carried out from January to December 2021. A purposive maximum variation sample of 10 dentists was interviewed in two focus groups. The interview guide was developed using the technology–organization–environment framework. The data was transcribed verbatim using otter.ai. The analysis involved immersion in the data and open coding. The conceptually related codes were synthesized into themes and subthemes.

Findings

The study found various Personnel, Technological and Organizational challenges, and potential solutions from those practicing Teledentistry. The challenges included operational cost, minimal financial returns, lack of awareness, hardware and software support, and other challenges related to the availability of specialization, accessibility, and institutional encouragement. They suggested Institutional Based Practice, staff training, hiring, development of government regulations, and supporting infrastructures such as designated space, central registry, internet, and using/building software to provide 3D images as solutions.

Conclusion

Teledentists face Personnel, Technological and Organizational challenges and related potential solutions from those practicing Teledentistry in Pakistan. Government should encourage Teledentistry to reduce long-term costs, encourage preventive services and enable rural access to dental care. They should also involve all stakeholders to develop regulations for practicing Teledentistry in Pakistan.
Application of machine learning techniques for predicting survival in ovarian cancer
Authors: Sorayaie Azar Amir , Babaei Rikan Samin , Naemi Amin , Bagherzadeh Mohasefi Jamshid , Pirnejad Habibollah , Bagherzadeh Mohasefi Matin , Wiil Uffe Kock
Published: December 2022

Background

Ovarian cancer is the fifth leading cause of mortality among women in the United States. Ovarian cancer is also known as forgotten cancer or silent disease. The survival of ovarian cancer patients depends on several factors, including the treatment process and the prognosis.

Methods

The ovarian cancer patients’ dataset is compiled from the Surveillance, Epidemiology, and End Results (SEER) database. With the help of a clinician, the dataset is curated, and the most relevant features are selected. Pearson’s second coefficient of skewness test is used to evaluate the skewness of the dataset. Pearson correlation coefficient is also used to investigate the associations between features. Statistical test is utilized to evaluate the significance of the features. Six Machine Learning (ML) models, including K-Nearest Neighbors , Support Vector Machine (SVM), Decision Tree (DT), Random Forest (RF), Adaptive Boosting (AdaBoost), and Extreme Gradient Boosting (XGBoost), are implemented for survival prediction in both classification and regression approaches. An interpretable method, Shapley Additive Explanations (SHAP), is applied to clarify the decision-making process and determine the importance of each feature in prediction. Additionally, DTs of the RF model are displayed to show how the model predicts the survival intervals.

Results

Our results show that RF (Accuracy = 88.72%, AUC = 82.38%) and XGBoost (Root Mean Squad Error (RMSE)) = 20.61%, R2 = 0.4667) have the best performance for classification and regression approaches, respectively. Furthermore, using the SHAP method along with extracted DTs of the RF model, the most important features in the dataset are identified. Histologic type ICD-O-3, chemotherapy recode, year of diagnosis, age at diagnosis, tumor stage, and grade are the most important determinant factors in survival prediction.

Conclusion

To the best of our knowledge, our study is the first study that develops various ML models to predict ovarian cancer patients’ survival on the SEER database in both classification and regression approaches. These ML algorithms also achieve more accurate results and outperform statistical methods. Furthermore, our study is the first study to use the SHAP method to increase confidence and transparency of the proposed models’ prediction for clinicians. Moreover, our developed models, as an automated auxiliary tool, can help clinicians to have a better understanding of the estimated survival as well as important features that affect survival.
Cost-effectiveness of pegfilgrastim versus filgrastim for prevention of chemotherapy-induced febrile neutropenia in patients with lymphoma: a systematic review
Authors: Gebremariam Girma Tekle , Fentie Atalay Mulu , Beyene Kebede , Sander Beate , Gebretekle Gebremedhin Beedemariam
Published: December 2022

Background

Febrile neutropenia (FN) is a prevalent and potentially life-threatening complication in patients with lymphoma receiving myelosuppressive chemotherapy. Pegfilgrastim is more effective than filgrastim as prophylaxis for FN. However, its usage has been limited because of its higher cost. Pegfilgrastim’s value for money remains unclear.

Objective

To systematically review the cost-effectiveness of pegfilgrastim compared to filgrastim as a primary or secondary prophylaxis for chemotherapy-induced FN among patients with lymphoma.

Methods

A systematic literature search was conducted in PubMed, EMBASE, Cochrane Library databases, and Google Scholar. The most widely used economic evaluations (cost-effectiveness analysis, cost-utility analysis and cost-benefit analysis) were included in the review. Data extraction was guided by the Consolidated Health Economic Evaluation Reporting Standards checklist, and the quality of reviewed articles was assessed using the Joanna Briggs Institute (JBI) checklist. Cost-effectiveness data were rigorously summarized and synthesized narratively. Costs were adjusted to US$ 2020.

Results

We identified eight economic evaluation studies (two cost-utility analyses, three cost-effectiveness analyses, and three studies reporting both cost-effectiveness and cost-utility analyses). Half of these studies were from Europe (n = 4), the other half were from Iran, USA, Canada, and Singapore. Six studies met > 80% of the JBI quality assessment criteria. Cost-effectiveness estimates in the majority (n = 6) of these studies were for Non-Hodgkin Lymphoma patients receiving myelosuppressive chemotherapy with high-risk of FN (> 20%). The studies considered a wide range of baseline FN risk (17–97.4%) and mortality rates (5.8–8.9%). Reported incremental cost-effectiveness ratios ranged from US$ 2199 to US$ 8,871,600 per quality-adjusted life-year (QALY) gained, dominant to US$ 44,358 per FN averted, and US$ 4261- US$ 7251 per life-years gained. The most influential parameters were medication and hospitalization costs, the relative risk of FN, and assumptions of mortality benefit.

Conclusions

Most studies showed that pegfilgrastim is cost-effective compared to filgrastim as primary and secondary prophylaxis for chemotherapy-induced FN among patients with lymphoma at a cost-effectiveness threshold of US$ 50,000 per QALY gained. The findings could assist clinicians and healthcare decision-makers to make informed decisions regarding resource allocation for the management of chemotherapy-induced FN in settings similar to those studied.
Who is protected? Determinants of hepatitis B infant vaccination completion among a prospective cohort of migrant workers in Thailand during the COVID-19 pandemic
Authors: Gilder Mary Ellen , Pateekhum Chanapat , Hashmi Ahmar , Aramrat Chanchanok , Aung Ko Ko , Miket Wimon , Chu Cindy S. , Win December , Bierhoff Marieke , Wiwattanacharoen Wichuda , Jiraporncharoen Wichuda , Angkurawaranon Chaisiri , McGready Rose
Published: December 2022

Background

Hepatitis B causes significant disease and death globally, despite the availability of effective vaccination. Migration likewise affects hundreds of millions of people annually, many of whom are women and children, and increases risks for poor vaccine completion and mother to child transmission of hepatitis B. In the neighbouring countries of Thailand and Myanmar, vaccine campaigns have made progress but little is known about the reach of these programs into migrant worker communities from Myanmar living in Thailand.

Methods

A cohort of 253 postpartum women (53 urban migrants in Chiang Mai and 200 rural migrants in Tak Province) were surveyed about their Hepatitis B knowledge and willingness to vaccinate their children between September 10, 2019 and March 30, 2019. They were subsequently followed to determine vaccine completion. When records of vaccination were unavailable at the birth facility, or visits were late, families were contacted and interviewed about vaccination elsewhere, and reasons for late or missed vaccines.

Results

Though women in Tak province displayed better knowledge of Hepatitis B and equal intention to vaccinate, they were 14 times less likely to complete Hepatitis B vaccination for their children compared to migrants in Chiang Mai. Tak women were largely undocumented, had private (non-profit) insurance and had more transient residence. In Chiang Mai migrant women were mostly documented and had full access to the Thai national health services. Though minor individual and facility-level differences may have contributed, the major driver of the disparity seems to be the place of migrants within local socio-political-economic systems. The COVID-19 pandemic further disproportionately affected Tak province migrants who faced severe travel restrictions hampering vaccination. Sixty percent of families who were lost to vaccine follow-up in Tak province could not be contacted by phone or home visit. Chiang Mai migrants, with 86.8% vaccine completion, nearly reached the target of 90%.

Conclusions

Achievement of high levels of hepatitis B vaccination in migrant communities is important and feasible, and requires inclusive policies that integrate migrants into national health and social services. This is more urgent than ever during the COVID-19 era.
lncRNA ZNRD1-AS1 promotes malignant lung cell proliferation, migration, and angiogenesis via the miR-942/TNS1 axis and is positively regulated by the m6A reader YTHDC2
Authors: Wang Jin , Tan Lirong , Yu Xueting , Cao Xiyuan , Jia Beibei , Chen Rui , Li Jianxiang
Published: December 2022

Rationale

Lung cancer is the most prevalent form of cancer and has a high mortality rate, making it a global public health concern. The N6-methyladenosine (m6A) modification is a highly dynamic and reversible process that is involved in a variety of essential biological processes. Using in vitro, in vivo, and multi-omics bioinformatics, the present study aims to determine the function and regulatory mechanisms of the long non-coding (lnc)RNA zinc ribbon domain-containing 1-antisense 1 (ZNRD1-AS1).

Methods

The RNAs that were bound to the m6A ‘reader’ were identified using YTH domain-containing 2 (YTHDC2) RNA immunoprecipitation (RIP)-sequencing. Utilizing methylated RIP PCR/quantitative PCR, pull-down, and RNA stability assays, m6A modification and ZNRD1-AS1 regulation were analyzed. Using bioinformatics, the expression levels and clinical significance of ZNRD1-AS1 in lung cancer were evaluated. Using fluorescent in situ hybridization and quantitative PCR assays, the subcellular location of ZNRD1-AS1 was determined. Using cell migration, proliferation, and angiogenesis assays, the biological function of ZNRD1-AS1 in lung cancer was determined. In addition, the tumor suppressor effect of ZNRD1-AS1 in vivo was validated using a xenograft animal model. Through bioinformatics analysis and in vitro assays, the downstream microRNAs (miRs) and competing endogenous RNAs were also predicted and validated.

Results

This study provided evidence that m6A modification mediates YTHDC2-mediated downregulation of ZNRD1-AS1 in lung cancer and cigarette smoke-exposed cells. Low levels of ZNRD1-AS1 expression were linked to adverse clinicopathological characteristics, immune infiltration, and prognosis. ZNRD1-AS1 overexpression was shown to suppress lung cancer cell proliferation, migration, and angiogenesis in vitro and in vivo, and to reduce tumor growth in nude mice. ZNRD1-AS1 expression was shown to be controlled by treatment of cells with either the methylation inhibitor 3-Deazaadenosine or the demethylation inhibitor Meclofenamic. Furthermore, the miR-942/tensin 1 (TNS1) axis was demonstrated to be the downstream regulatory signaling pathway of ZNRD1-AS1.

Conclusions

ZNRD1-AS1 serves an important function and has clinical relevance in lung cancer. In addition, the findings suggested that m6A modification could mediate the regulation of the ZNRD1-AS1/miR-942/TNS1 axis via the m6A reader YTHDC2.

Graphical Abstract
Noninvasive prenatal diagnosis targeting fetal nucleated red blood cells
Authors: Chen Yanyu , Wu Zhuhao , Sutlive Joseph , Wu Ke , Mao Lu , Nie Jiabao , Zhao Xing-Zhong , Guo Feng , Chen Zi , Huang Qinqin
Published: December 2022

Noninvasive prenatal diagnosis (NIPD) aims to detect fetal-related genetic disorders before birth by detecting markers in the peripheral blood of pregnant women, holding the potential in reducing the risk of fetal birth defects. Fetal-nucleated red blood cells (fNRBCs) can be used as biomarkers for NIPD, given their remarkable nature of carrying the entire genetic information of the fetus. Here, we review recent advances in NIPD technologies based on the isolation and analysis of fNRBCs. Conventional cell separation methods rely primarily on physical properties and surface antigens of fNRBCs, such as density gradient centrifugation, fluorescence-activated cell sorting, and magnetic-activated cell sorting. Due to the limitations of sensitivity and purity in Conventional methods, separation techniques based on micro-/nanomaterials have been developed as novel methods for isolating and enriching fNRBCs. We also discuss emerging methods based on microfluidic chips and nanostructured substrates for static and dynamic isolation of fNRBCs. Additionally, we introduce the identification techniques of fNRBCs and address the potential clinical diagnostic values of fNRBCs. Finally, we highlight the challenges and the future directions of fNRBCs as treatment guidelines in NIPD.

Graphical Abstract
Conservative versus surgical treatment of foot drop in peroneal nerve entrapment: rationale and design of a prospective, multi-centre, randomized parallel-group controlled trial
Authors: Oosterbos Christophe , Rummens Sofie , Bogaerts Kris , Hoornaert Sophie , Weyns Frank , Dubuisson Annie , Lemmens Robin , Theys Tom
Published: December 2022

Background

High-quality evidence is lacking to support one treatment strategy over another in patients with foot drop due to peroneal nerve entrapment. This leads to strong variation in daily practice.

Methods/design

The FOOTDROP (Follow-up and Outcome of Operative Treatment with Decompressive Release Of The Peroneal nerve) trial is a randomized, multi-centre study in which patients with peroneal nerve entrapment and persistent foot drop, despite initial conservative treatment, will be randomized 10 (± 4) weeks after onset between non-invasive treatment and surgical decompression. The primary endpoint is the difference in distance covered during the 6-min walk test between randomization and 9 months later. Time to recovery is the key secondary endpoint. Other secondary outcome measures encompass ankle dorsiflexion strength (MRC score and isometric dynamometry), gait assessment (10-m walk test, functional ambulation categories, Stanmore questionnaire), patient-reported outcome measures (EQ5D-5L), surgical complications, neurological deficits (sensory changes, motor scores for ankle eversion and hallux extension), health economic assessment (WPAI) and electrodiagnostic assessment.

Discussion

The results of this randomized trial may elucidate the role of surgical decompression of the peroneal nerve and aid in clinical decision-making.

Trial registration

ClinicalTrials.gov NCT04695834. Registered on 4 January 2021.
Effects of osteopathic manipulative treatment associated with pain education and clinical hypnosis in individuals with chronic low back pain: study protocol for a randomized sham-controlled clinical trial
Authors: Luchesi Guilherme Luis Santana , da Silva Anne Kastelianne França , Amaral Otávio Henrique Borges , de Paula Vanessa Cristina Godoi , Jassi Fabrício José
Published: December 2022

Background

Patients with chronic low back pain (CLBP) suffer with functional, social, and psychological aspects. There is a growing number of studies with multimodal approaches in the management of these patients, combining physical and behavioral therapies such as osteopathic manipulative treatment, associating pain education and clinical hypnosis. The aim of the present study will be to evaluate the effects of osteopathic manipulative treatment (OMT) associated with pain neuroscience education (PNE) and clinical hypnosis (CH) on pain and disability in participants with CLBP compared to PNE, CH, and sham therapy.

Methods

A randomized controlled clinical trial will be conducted in participants aged 20–60 years with CLBP who will be divided into two groups. Group 1 will receive PNE and CH associated with OMT, and G2 will receive PNE, CH, and sham therapy. In both groups, 4 interventions of a maximum of 50 min and with an interval of 7 days will be performed. As primary outcomes, pain (numerical pain scale), pressure pain threshold (pressure algometer), and disability (Oswestry Disability Questionnaire) will be evaluated and, as a secondary outcome, global impression of improvement (Percent of Improvement Scale), central sensitization (Central Sensitization Questionnaire), biopsychosocial aspects (Start Beck Toll Questionnaire), and behavior of the autonomic nervous system (heart rate variability) will be assessed. Participants will be evaluated in the pre-intervention moments, immediately after the end of the protocol and 4 weeks after the procedures. Randomization will be created through a simple randomized sequence and the evaluator will be blinded to the allocation of intervention groups.

Discussion

The guidelines have been encouraging multimodal, biopsychosocial approaches for patients with CLBP; in this sense, the results of this study can help clinicians and researchers in the implementation of a model of treatment strategy for these patients. In addition, patients may benefit from approaches with minimal risk of deleterious effects and low cost. In addition, it will enable the addition of relevant elements to the literature, with approaches that interact and do not segment the body and brain of patients with CLBP, allowing new studies in this scenario.

Trials registration

Date: September 4, 2021/Number: NCT05042115.
Simultaneous 18F-FDG PET/MR metabolic and structural changes in visual snow syndrome and diagnostic use
Authors: Van Laere Koen , Ceccarini Jenny , Gebruers Juanito , Goffin Karolien , Boon Elizabet
Published: December 2022

Purpose

Visual snow syndrome (VSS) is a recently recognized chronic neurologic condition characterized by the constant perceiving of tiny flickering dots throughout the entire visual field. Metabolic overactivity and grey matter volume increase in the lingual gyrus has been reported. We investigated this by 18F-FDG PET/MR in comparison to healthy controls. Aside from voxel-based characterization, the classification accuracy of volume-of-interest (VOI)-based multimodal assessment was evaluated, also in comparison with visual analysis.

Methods

Simultaneous 18F-FDG PET and MR imaging was performed in 7 patients with VSS (24.6 ± 5.7 years; 5 M/2F) and 15 age-matched healthy controls (CON) (28.0 ± 5.3 years; 8 M/7F). SPM12 and voxel-based morphometric analysis was performed. A VOI-based discriminant analysis was performed with relative 18F-FDG uptake, MR grey matter (GM) volumes and their combination. A visual analysis was done by two blinded experienced readers.

Results

Relative increased hypermetabolism was found in VSS patients in the lingual gyrus and cuneus (pFWE < 0.05, peak change + 24%), and hypometabolism in the mesiotemporal cortex (pheight,uncorr < 0.001, peak change − 14%). VSS patients also had increased GM volume in the limbic system and frontotemporal cortex bilaterally (pFWE < 0.05), and in the left secondary and associative visual cortex and in the left lingual gyrus (pheight,uncorr < 0.001). Discriminant analysis resulted in 100% correct classification accuracy for 18F-FDG with lingual gyrus, cuneus and lateral occipital lobe (BA 17 and BA 18) as main discriminators. Unimodal MR- and combined 18F-FDG + MR classification resulted in an accuracy of 91% and 95%, respectively. Visual analysis of 18F-FDG was highly observer dependent.

Conclusion

Patients with VSS have highly significant structural and metabolic abnormalities in the visual and limbic system. VOI-based discriminant analysis of 18F-FDG PET allows reliable individual classification versus controls, whereas visual analysis of experienced observers was highly variable. Further investigation in larger series, also in comparison to VSS mimicking disorders such as migraine, is warranted.

Trail registration: Retrospectively registered at clinicaltrials.gov under NCT05569733 on Oct 5, 2022.
Cost-effectiveness analysis of sintilimab plus pemetrexed and platinum versus chemotherapy alone as first-line treatment in metastatic non-squamous non–small cell lung cancer in China
Authors: Liu Huiqin , Wang Ying , He Qi
Published: December 2022

Objective

In frst-line treatment of advanced or metastatic nonsquamous non-small-cell lung cancer (NSCLC), the ORIENT-11 study demonstrated a signifcant progression-free survival and overall survival for sintilimab plus chemotherapy in comparison with chemotherapy alone. But the cost-effectiveness of the two treatment schemes is unclear in China. The objective of the current study was to evaluate the cost efectiveness of sintilimab plus chemotherapy versus Platinum-based chemotherapy for locally advanced or metastatic squamous NSCLC in China.

Methods

We performed an economic evaluation from the perspective of the Chinese healthcare system using a partitioned survival model with three mutually exclusive health states: progression free, post-progression, and death. The circulation cycle of the model was 3 weeks and the study time limit was 10 years. Efficacy data were obtained from the ORIENT-11 clinical trial. Cost and utility values were derived from published studies and online price databases. The primary outcomes of the model were quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). One-way sensitivity analysis and probability sensitivity analysis were used to verify the robustness of the base-case analysis results.

Results

Sintilimab plus chemotherapy provided an additional 0.6 QALYs. The total cost per patient was CNY¥413,273.16 for sintilimab plus chemotherapy and CNY¥280,695.23 for Platinum-based chemotherapy. The ICER for sintilimab plus chemotherapy was CNY¥220,963.22/QALY. Sensitivity analyses found the results to be most sensitive to the cost of pemetrexed and utilities of PF state. In the probabilistic sensitivity analysis, sintilimab was cost-efective in 78.6% of the simulations, assuming a willingness-to-pay threshold (WTP) of CNY¥242,928 per QALY.

Conclusion

Compared with chemotherapy alone, the sintilimab plus chemotherapy is likely to be a cost-effective option as the first-line treatment for locally advanced or metastatic nonsquamous NSCLC in China.
Wireless edge device intelligent task offloading in mobile edge computing using hyper-heuristics
Authors: Vijayaram B. , Vasudevan V.
Published: December 2022

To overcome with the computation limitation of resource-constrained wireless IoT edge devices, providing an efficient task computation offloading and resource allocation in distributed mobile edge computing environment is consider as a challenging and promising solution. Hyper-heuristic in recent times is gaining popularity due to its general applicability of same solution to solve different types of problems. Hyper-heuristic is generally a heuristic method or framework which iteratively evaluates and chooses the best low-level heuristic, to solve different types of problems. In this paper, we try to solve wireless device task offloading in mobile edge computing, which is a non-convex and NP-Hard problem by using a proposed novel Hyper-Heuristic Framework using Stochastic Heuristic Selection (HHFSHS) using Contextual Multi-Armed Bandit (CMAB) with Epsilon-Decreasing strategy, considering two key Quality of Service (QoS) objectives computation time and energy consumption. These multiobjective criteria are modeled as single-objective optimization problem with the goal to minimize latency and energy consumption of wireless devices without losing the pareto optimality. Finally, evaluate its performance by comparing with other individual meta-heuristic algorithms.
Gut microbiota and cardiac arrhythmia: a pharmacokinetic scope
Authors: Nabeh Omnia Azmy
Published: December 2022

Background

Dealing with cardiac arrhythmia is a difficult challenge. Choosing between different anti-arrhythmic drugs (AADs) while being cautious about the pro-arrhythmic characteristics of some of these drugs and their diverse interaction with other drugs is a real obstacle.

Main body

Gut microbiota (GM), in our bodies, are now being considered as a hidden organ which can regulate our immune system, digest complex food, and secrete bioactive compounds. Yet, GM are encountered in the pathophysiology of arrhythmia and can affect the pharmacokinetics of AADs, as well as some anti-thrombotics, resulting in altering their bioavailability, therapeutic function and may predispose to some of their unpleasant adverse effects.

Conclusions

Knowledge of the exact role of GM in the pharmacokinetics of these drugs is now essential for better understanding of the art of arrhythmia management. Also, it will help deciding when to consider probiotics as an adjunctive therapy while treating arrhythmia. This should be discovered in the near future.
Acute pancreatitis complicated by hemolytic uremic syndrome: a pediatric case
Authors: Taner Sevgin , Karaçay Işıl Ezel Taşkın , Arslan İlknur
Published: December 2022

Background

Hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and acute kidney injury. The acute pancreatitis-associated HUS is a rare entity, and this case is one of the few pediatric cases reported.

Case presentation

A 17-year-old girl referred to the emergency department with complaints of abdominal pain, fever, and vomiting. The skin and sclera were icteric. Murphy’s sign was positive. Hemogram was normal, biochemical analysis revealed an increase in liver function tests and cholestasis enzymes. Abdominal CT revealed multiple stones in the hydropic gallbladder lumen and the pancreas was edematous. With a diagnosis of acute pancreatitis supportive treatment was started. Acute kidney failure, cholestasis, anemia, and thrombocytopenia developed at the 2nd day of follow-up. Thrombotic thrombocytopenic purpura was excluded with normal ADAMTS-13 level. Intermittent hemodialysis and plasma exchange (PE) treatments were initiated, considering pancreatitis-related HUS. On the 3rd day of PE, the patient’s urine output exceeded 1 cc/kg per hour. No schistocyte was found in the peripheral smear after 7 PE and 5 hemodialysis sessions. Anemia, thrombocytopenia, and kidney functions improved. On the 15th day of the follow-up, endoscopic retrograde cholangiopancreatography performed, and gallbladder stones were removed.

Conclusion

The pathogenesis of HUS developing after acute pancreatitis is not fully understood. The mechanism proposed is that acute pancreatitis triggers cytokine release, resulting in endothelial damage and HUS. In conclusion, HUS may rarely develop in patients with acute pancreatitis. With the early diagnosis and appropriate treatment, the kidney functions can be completely normalized.
Klebsiella infections in a pediatric intensive care unit: incidence, antimicrobial susceptibility, and resistance genes
Authors: El-Nawawy Ahmed , Meheissen Marwa A. , Badr Ahmed M. , Antonios Manal A. M.
Published: December 2022

Background

Infections with multidrug-resistant K. pneumoniae is associated with high morbidity and mortality especially among critically ill patients. This was the main principle to conduct a detailed study about this organism, its resistance pattern, and type of its resistance genes

Subjects and methods

A cross-sectional study was carried out in a pediatric intensive care unit on patients with age range from 1 month to 12 years over a period of 1 year with positive K. pneumoniae using standard microbiological culture and antibiogram sensitivity testing. All collected samples were processed using multiplex PCR technique to identify the most relevant resistant genes.

Results

Forty-four patients had 54 positive cultures for K. pneumoniae, out of which 17 patients (38.6%) passed away. The most prevalent-resistant gene was New Delhi metallo-beta lactamase (NDM) gene (65.4%) followed by cefotaximase (CTX-M) gene (57.7%). Extensively drug-resistant K. pneumoniae was detected in (15.9%) of the results and was proved to be independent risk factor increasing mortality odds 139 folds.

Conclusion

The evolution of resistance of Klebsiella pneumoniae was proved to be associated with a high mortality rate. Continuous widespread surveillance of Klebsiella pathogen focusing on identification of resistance genes and antibiotic resistance pattern is highly recommended.
Advances in modeling boundary layer turbulence and its effects on motion independent aerodynamic force of bridge decks
Authors: Zhao Lin , Wu Fengying , Liu Zhenbiao , Yan Aiguo , Ge Yaojun
Published: December 2022

Wind tunnel tests remain crucial to solving the wind-induced issues, such as buffeting. The turbulence impacts on the aerodynamic forces is vital to buffeting responses of a bridge, which has been neglected, for that traditional passive wind tunnel test simulations are mainly to perform smaller turbulence integral scale, compared with the reduced-scale similarity. A turbulence hybrid simulation device that integrates vibrating grids and active fans was proposed, realizing a detectable adjustment of the bi-directional pulse energy of the incoming turbulence. The simulation development of the active turbulence in the wind tunnel test was reviewed briefly firstly. To investigate turbulence influence on the aerodynamic forces, the pressure-measurement wind tunnel tests of typical bridge decks were carried out in active control wind tunnel. The impacts of different incoming turbulence on the aerodynamic force and buffeting response were furtherly discussed. Results revealed that the bi-direction (along-wind and vertical wind) influenced aerodynamic forces synergistically. Otherwise, turbulence integral scale strongly influenced aerodynamic characteristics, such as buffeting responses, notably, the buffeting responses obtained in active controlled wind tunnel would be reasonable for a safety evaluation of bridges under construction and operation.
What Caused Racial Disparities in Particulate Exposure to Fall? New Evidence from the Clean Air Act and Satellite-Based Measures of Air Quality
Authors: Currie Janet , Voorheis John , Walker Reed
Published: December 2022

This project links administrative census microdata to spatially continuous measures of particulate pollution (PM2.5) to first document and then decompose the key drivers of convergence in black-white pollution exposure differences. We use quantile regression to show that a significant portion of the convergence in Black-White exposure is attributable to differential impacts of the Clean Air Act (CAA) in Black and White communities. Areas with larger Black populations saw greater CAA-related declines in PM2.5. We show that the CAA can account for over 60 percent of the racial convergence in PM2.5 pollution exposure in the United States since 2000. (JEL J15, K32, Q51, Q53, Q58)
Judging Judge Fixed Effects
Authors: Frandsen Brigham , Lefgren Lars , Leslie Emily
Published: December 2022

We propose a nonparametric test for the exclusion and monotonicity assumptions invoked in instrumental variable (IV) designs based on the random assignment of cases to judges. We show its asymptotic validity and demonstrate its finite-sample performance in simulations. We apply our test in an empirical setting from the literature examining the effects of pretrial detention on defendant outcomes in New York. When the assumptions are not satisfied, we propose weaker versions of the usual exclusion and monotonicity restrictions under which the IV estimator still converges to a proper weighted average of treatment effects. (JEL H76, K41)
Retail Pharmacies and Drug Diversion during the Opioid Epidemic
Authors: Janssen Aljoscha , Zhang Xuan
Published: December 2022

This study investigates the role of retail pharmacy ownership in the opioid epidemic. Using data of prescription opioid orders, we show that compared with chain pharmacies, independent pharmacies dispense 39.1 percent more opioids and 60.5 percent more OxyContin. After an independent pharmacy becomes a chain pharmacy, opioid dispensing decreases. Using the OxyContin reformulation, which reduced nonmedical demand but not the legitimate medical demand, we show that at least one-third of the difference in the amount of OxyContin dispensed can be attributed to nonmedical demand. We show that differences in competitive pressure and whether pharmacists own the pharmacy drive our estimates. (JEL G32, I12, L22, L81)
Inefficient Water Pricing and Incentives for Conservation
Authors: Chakravorty Ujjayant , Dar Manzoor H. , Emerick Kyle
Published: December 2022

Farmers often buy water using fixed fees—rather than with marginal prices. We use two randomized controlled trials in Bangladesh to study the relationship between marginal prices, adoption of a water-saving technology, and water usage. Our first experiment shows that the technology only saves water when farmers face marginal prices. Our second experiment finds that an encouragement to voluntarily convert to hourly pumping charges does not save water. Taken together, efforts to conserve water work best when farmers face marginal prices, but simply giving an option for marginal pricing is insufficient to trigger water-saving investments and reduce irrigation demands. (JEL O13, Q12, Q15, Q16, Q25)
The Government Spending Multiplier in a Multisector Economy
Authors: Bouakez Hafedh , Rachedi Omar , Santoro Emiliano
Published: December 2022

We study the effects of aggregate government spending shocks in a production network economy where sectors differ in their price rigidity, factor intensities, use of intermediate inputs, and contribution to final demand. The model implies an aggregate value-added multiplier that is 75 percent (and $0.32) larger than that obtained in the average one-sector economy. This amplification is mainly driven by input–output linkages and—to a lesser extent—sectoral heterogeneity in price rigidity. Aggregate government spending shocks also lead to heterogeneous responses of sectoral value added, which are larger among upstream industries. We present novel empirical evidence supporting this prediction. (JEL E12, E16, E23, E43, E52, E62, H50)