bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of the ferroptosis-related long non-coding RNAs signature to improve the prognosis prediction and immunotherapy response in patients with NSCLC
Authors: Li Meng , Zhang Yanpeng , Fan Meng , Ren Hui , Chen Mingwei , Shi Puyu
Published: December 2021

Background

Non-small cell lung cancer (NSCLC) is the most prevalent type of lung carcinoma with an unfavorable prognosis. Ferroptosis is involved in the development of multiple cancers. Whereas, the prognostic value of ferroptosis-related lncRNAs in NSCLC remains uncertain.

Methods

Gene expression profiles and clinical information of NSCLC were retrieved from the TCGA database. Ferroptosis-related genes (FRGs) were explored in the FerrDb database and previous studies, ferroptosis-related lncRNAs (FRGs-lncRNAs) were identified by the correlation analysis and the LncTarD database. The differentially expressed FRGs-lncRNAs were screened and FRGs-lncRNAs associated with the prognosis were explored by univariate Cox regression analysis and Kaplan–Meier survival analysis. Then, an FRGs-lncRNAs signature was constructed and verified by the Lasso-penalized Cox analysis. Finally, the potential correlation between risk score, immune checkpoint genes, and chemotherapeutic sensitivity was further investigated.

Results

129 lncRNAs with a potential regulatory relationship with 59 differentially expressed FRGs were found in NSCLC, of which 10 were related to the prognosis of NSCLC (P < 0.05). 9 prognostic-related FRGs-lncRNAs were used to construct the prognostic model and stratify NSCLC patients into high- and low-risk groups. A worse outcome was found in patients with high risk (P < 0.05). Moreover, a good predictive capacity of this signature in predicting NSCLC prognosis was confirmed. Additionally, 45 immune checkpoint genes and 4 chemotherapeutics drugs for NSCLC were identified to be correlated with the risk score.

Conclusion

A novel FRGs-lncRNAs signature was successfully constructed, which may contribute to improving the management strategies of NSCLC.
Changes over time in inflammatory and structural lesions at the sacroiliac joint in children with spondyloarthritis exposed and unexposed to tumor necrosis factor inhibitor
Authors: Brandon Timothy G. , Xiao Rui , Peterson Rosemary G. , Chauvin Nancy A. , Francavilla Michael L. , Biko David M. , Rumsey Dax G. , Stoll Matthew L. , Weiss Pamela F.
Published: December 2021

Background

The objective of this work was to describe magnetic resonance imaging (MRI) changes over time in inflammatory and structural lesions at the sacroiliac joint (SIJ) in children with spondyloarthritis (SpA) exposed and unexposed to tumor necrosis factor inhibitor (TNFi).

Methods

This was a retrospective, multicenter study of SpA patients with suspected or confirmed sacroiliitis who underwent at ≥2 pelvic MRI scans. Images were reviewed independently by 3 radiologists and scored for inflammatory and structural changes using the Spondyloarthritis Research Consortium of Canada (SPARCC) SIJ inflammation score (SIS) and structural score (SSS). Longitudinal, quantitative changes in patient MRI scans were measured using descriptive statistics and stratified by TNFi exposure. We used an average treatment effects (ATE) regression model to explore the average effect of TNFi exposure over time on inflammatory and structural lesions, adjusting for baseline lesion scores.

Results

Forty-six subjects were evaluated using the SIS (n = 45) and SSS (n = 18). Median age at baseline imaging was 13.6 years, 63% were male and 71% were white. Twenty-three subjects (50%) were TNFi exposed between MRI studies. The median change in SIS in TNFi exposed and unexposed subjects with a baseline SIS ≥0 was − 20.7 and − 14.3, respectively (p = 0.09). Eleven (85%) TNFi exposed and 8 (89%) unexposed subjects with a baseline SIS ≥0 met the SIS minimal clinically important difference (MCID; ≥2.5). Using the ATE model adjusted for baseline SIS, the average effect of TNFi on SIS in patients with a baseline SIS ≥2 was − 14.5 (p < 0.01). Unadjusted erosion change score was significantly worse in TNFi unexposed versus exposed subjects (p = 0.03) but in the ATE model the effect of TNFi was not significant.

Conclusion

This study quantitatively describes how lesions in the SIJs on MRI change over time in patients exposed to TNFi versus unexposed. Follow-up imaging in TNFi exposed patients showed greater improvement than the unexposed group by most metrics, some of which reached statistical significance. Surprisingly, a majority of TNFi unexposed children with a baseline SIS≥2 met the SIS MCID. Additional studies assessing the short and long-term effects of TNFi on inflammatory and structural changes in juvenile SpA are needed.
Downregulating expression of OPTN elevates neuroinflammation via AIM2 inflammasome- and RIPK1-activating mechanisms in APP/PS1 transgenic mice
Authors: Cao Long-Long , Guan Pei-Pei , Zhang Shen-Qing , Yang Yi , Huang Xue-Shi , Wang Pu
Published: December 2021

Background

Neuroinflammation is thought to be a cause of Alzheimer’s disease (AD), which is partly caused by inadequate mitophagy. As a receptor of mitophagy, we aimed to reveal the regulatory roles of optineurin (OPTN) on neuroinflammation in the pathogenesis of AD.

Methods

BV2 cells and APP/PS1 transgenic (Tg) mice were used as in vitro and in vivo experimental models to determine the regulatory roles of OPTN in neuroinflammation of AD. Sophisticated molecular technologies including quantitative (q) RT-PCR, western blot, enzyme linked immunosorbent assay (ELISA), co-immunoprecipitation (Co-IP) and immunofluorescence (IF) were employed to reveal the inherent mechanisms.

Results

As a consequence, key roles of OPTN in regulating neuroinflammation were identified by depressing the activity of absent in melanoma 2 (AIM2) inflammasomes and receptor interacting serine/threonine kinase 1 (RIPK1)-mediated NF-κB inflammatory mechanisms. In detail, we found that expression of OPTN was downregulated, which resulted in activation of AIM2 inflammasomes due to a deficiency in mitophagy in APP/PS1 Tg mice. By ectopic expression, OPTN blocks the effects of Aβ oligomer (Aβo) on activating AIM2 inflammasomes by inhibiting mRNA expression of AIM2 and apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), leading to a reduction in the active form of caspase-1 and interleukin (IL)-1β in microglial cells. Moreover, RIPK1 was also found to be negatively regulated by OPTN via ubiquitin protease hydrolysis, resulting in the synthesis of IL-1β by activating the transcriptional activity of NF-κB in BV2 cells. As an E3 ligase, the UBAN domain of OPTN binds to the death domain (DD) of RIPK1 to facilitate its ubiquitination. Based on these observations, ectopically expressed OPTN in APP/PS1 Tg mice deactivated microglial cells and astrocytes via the AIM2 inflammasome and RIPK-dependent NF-κB pathways, leading to reduce neuroinflammation.

Conclusions

These results suggest that OPTN can alleviate neuroinflammation through AIM2 and RIPK1 pathways, suggesting that OPTN deficiency may be a potential factor leading to the occurrence of AD.
The impact of natural disasters on the spread of COVID-19: a geospatial, agent-based epidemiology model
Authors: de Vries Maximillian Van Wyk , Rambabu Lekaashree
Published: December 2021

Background

Natural disasters and infectious diseases result in widespread disruption to human health and livelihood. At the scale of a global pandemic, the co-occurrence of natural disasters is inevitable. However, the impact of natural disasters on the spread of COVID-19 has not been extensively evaluated through epidemiological modelling.

Methods

We create an agent-based epidemiology model based on COVID-19 clinical, epidemiological, and geographic data. We first model 35 scenarios with varying natural disaster timing and duration for a COVID-19 outbreak in a theoretical region. We then evaluate the potential effect of an eruption of Vesuvius volcano on the spread of COVID-19 in Campania, Italy.

Results

In a majority of cases, the occurrence of a natural disaster increases the number of disease related fatalities. For a natural disaster fifty days after infection onset, the median increase in fatalities is 2, 59, and 180% for a 2, 14, and 31-day long natural disaster respectively, when compared to the no natural disaster scenario. For the Campania case, the median increase in fatalities is 1.1 and 2.4 additional fatalities per 100,000 for eruptions on day 1 and 100 respectively, and 60.0 additional fatalities per 100,000 for an eruption close to the peak in infections (day 50).

Conclusion

Our results show that the occurrence of a natural disaster in most cases leads to an increase in infection related fatalities, with wide variance in possible outcomes depending on the timing of the natural disaster relative to the peak in infections and the duration of the natural disaster.
Transforming social norms to improve girl-child health and well-being: a realist evaluation of the Girls’ Holistic Development program in rural Senegal
Authors: Kohli Anjalee , Shaw Bryan , Guntzberger Mathilde , Aubel Judi , Coulibaly Mamadou , Igras Susan
Published: December 2021

Background

Early adolescence is a critical period where social norms, attitudes, and behaviors around gender equality form. Social norms influence adolescent choices and behaviors and are reinforced by caregivers and community members, affecting girls’ reproductive health and educational opportunities. Understanding how to shift these often-interconnected norms to delay child marriage, pregnancy and keep girls in school requires understanding of the structure and dynamics of family and community systems. The Senegalese and American non-governmental organization, the Grandmothers Project—Change through Culture, seeks to address these intertwined factors through innovative community change strategies that build on the specific structure and values of West African collectivist cultures.

Methods

The Girls’ Holistic Development approach in rural Vélingara, Senegal posits that by increasing recognition, knowledge and empowerment of elder community women and reinforcing intergenerational communication and decision-making, community members including girls will support and advocate on behalf of girls’ interests and desires. We assessed the Girls Holistic Development approach using Realist Evaluation with a mixed-method, quasi-experimental design with a comparison population. We examined differences in intergenerational communication, decision-making and descriptive and injunctive norms related to early marriage, pregnancy and schooling.

Results

After 18 months, intergenerational communication was more likely, grandmothers felt more valued in their communities, adolescent girls felt more supported with improved agency, and norms were shifting to support delayed marriage and pregnancy and keeping girls in school. Grandmothers in intervention villages were statistically significantly more likely to be perceived as influential decision-makers by both VYA girls and caregivers for marriage and schooling decisions compared to girls and caregivers in comparison villages.

Conclusions

This realist evaluation demonstrated shift in social norms, particularly for VYA girls, in intervention villages favoring delaying girls’ marriage, preventing early pregnancy and keeping girls in school along with increased support for and action by grandmothers to support girls and their well-being related to these same outcomes. These shifts represent greater community social cohesion on girl-child issues. This research helps explain the linkage between social norms and girls’ reproductive health and education outcomes and demonstrates that normative shifts can lead to behavior change via collective community action mechanisms.
LPI-EnEDT: an ensemble framework with extra tree and decision tree classifiers for imbalanced lncRNA-protein interaction data classification
Authors: Peng Lihong , Yuan Ruya , Shen Ling , Gao Pengfei , Zhou Liqian
Published: December 2021

Background

Long noncoding RNAs (lncRNAs) have dense linkages with various biological processes. Identifying interacting lncRNA-protein pairs contributes to understand the functions and mechanisms of lncRNAs. Wet experiments are costly and time-consuming. Most computational methods failed to observe the imbalanced characterize of lncRNA-protein interaction (LPI) data. More importantly, they were measured based on a unique dataset, which produced the prediction bias.

Results

In this study, we develop an Ensemble framework (LPI-EnEDT) with Extra tree and Decision Tree classifiers to implement imbalanced LPI data classification. First, five LPI datasets are arranged. Second, lncRNAs and proteins are separately characterized based on Pyfeat and BioTriangle and concatenated as a vector to represent each lncRNA-protein pair. Finally, an ensemble framework with Extra tree and decision tree classifiers is developed to classify unlabeled lncRNA-protein pairs. The comparative experiments demonstrate that LPI-EnEDT outperforms four classical LPI prediction methods (LPI-BLS, LPI-CatBoost, LPI-SKF, and PLIPCOM) under cross validations on lncRNAs, proteins, and LPIs. The average AUC values on the five datasets are 0.8480, 0,7078, and 0.9066 under the three cross validations, respectively. The average AUPRs are 0.8175, 0.7265, and 0.8882, respectively. Case analyses suggest that there are underlying associations between HOTTIP and Q9Y6M1, NRON and Q15717.

Conclusions

Fusing diverse biological features of lncRNAs and proteins and exploiting an ensemble learning model with Extra tree and decision tree classifiers, this work focus on imbalanced LPI data classification as well as interaction information inference for a new lncRNA (or protein).
Dysregulated splicing factor SF3B1 unveils a dual therapeutic vulnerability to target pancreatic cancer cells and cancer stem cells with an anti-splicing drug
Authors: Alors-Perez Emilia , Blázquez-Encinas Ricardo , Alcalá Sonia , Viyuela-García Cristina , Pedraza-Arevalo Sergio , Herrero-Aguayo Vicente , Jiménez-Vacas Juan M. , Mafficini Andrea , Sánchez-Frías Marina E. , Cano María T. , Abollo-Jiménez Fernando , Marín-Sanz Juan A. , Cabezas-Sainz Pablo , Lawlor Rita T. , Luchini Claudio , Sánchez Laura , Sánchez-Hidalgo Juan M. , Ventura Sebastián , Martin-Hijano Laura , Gahete Manuel D. , Scarpa Aldo , Arjona-Sánchez Álvaro , Ibáñez-Costa Alejandro , Sainz Bruno , Luque Raúl M. , Castaño Justo P.
Published: December 2021

Background

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, requiring novel treatments to target both cancer cells and cancer stem cells (CSCs). Altered splicing is emerging as both a novel cancer hallmark and an attractive therapeutic target. The core splicing factor SF3B1 is heavily altered in cancer and can be inhibited by Pladienolide-B, but its actionability in PDAC is unknown. We explored the presence and role of SF3B1 in PDAC and interrogated its potential as an actionable target.

Methods

SF3B1 was analyzed in PDAC tissues, an RNA-seq dataset, and publicly available databases, examining associations with splicing alterations and key features/genes. Functional assays in PDAC cell lines and PDX-derived CSCs served to test Pladienolide-B treatment effects in vitro, and in vivo in zebrafish and mice.

Results

SF3B1 was overexpressed in human PDAC and associated with tumor grade and lymph-node involvement. SF3B1 levels closely associated with distinct splicing event profiles and expression of key PDAC players (KRAS, TP53). In PDAC cells, Pladienolide-B increased apoptosis and decreased multiple tumor-related features, including cell proliferation, migration, and colony/sphere formation, altering AKT and JNK signaling, and favoring proapoptotic splicing variants (BCL-XS/BCL-XL, KRASa/KRAS, Δ133TP53/TP53). Importantly, Pladienolide-B similarly impaired CSCs, reducing their stemness capacity and increasing their sensitivity to chemotherapy. Pladienolide-B also reduced PDAC/CSCs xenograft tumor growth in vivo in zebrafish and in mice.

Conclusion

SF3B1 overexpression represents a therapeutic vulnerability in PDAC, as altered splicing can be targeted with Pladienolide-B both in cancer cells and CSCs, paving the way for novel therapies for this lethal cancer.
A randomised controlled trial testing the efficacy of Fit after COVID, a cognitive behavioural therapy targeting severe post-infectious fatigue following COVID-19 (ReCOVer): study protocol
Authors: Kuut T. A. , Müller F. , Aldenkamp A. , Assmann-Schuilwerve E. , Braamse A. , Geerlings S. E. , Gibney K. B. , Kanaan R. A. A. , Nieuwkerk P. , Olde Hartman T. C. , Pauëlsen D. , Prins M. , Slieker K. , Van Vugt M. , Bleeker-Rovers C. P. , Keijmel S. P. , Knoop H.
Published: December 2021

Background

Coronavirus disease 2019 (COVID-19) results in debilitating long-term symptoms, often referred to as Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), in a substantial subgroup of patients. One of the most prevalent symptoms following COVID-19 is severe fatigue. Prompt delivery of cognitive behavioural therapy (CBT), an evidence-based treatment that has shown benefit in reducing severe fatigue in other conditions, may reduce post-COVID-19 fatigue. Based on an existing CBT protocol, a blended intervention of 17 weeks, Fit after COVID, was developed to treat severe fatigue after the acute phase of infection with SARS-CoV-2.

Method

The ReCOVer study is a multicentre 2-arm randomised controlled trial (RCT) to test the efficacy of Fit after COVID on severe post-infectious fatigue. Participants are eligible if they report severe fatigue 3 up to and including 12 months following COVID-19. One hundred and fourteen participants will be randomised to either Fit after COVID or care as usual (ratio 1:1). The primary outcome, the fatigue severity subscale of the Checklist Individual Strength (CIS-fatigue), is assessed in both groups before randomisation (T0), directly post CBT or following care as usual (T1), and at follow-up 6 months after the second assessment (T2). In addition, a long-term follow-up (T3), 12 months after the second assessment, is performed in the CBT group only. The primary objective is to investigate whether CBT will lead to a significantly lower mean fatigue severity score measured with the CIS-fatigue across the first two follow-up assessments (T1 and T2) as compared to care as usual. Secondary objectives are to determine the proportion of participants no longer being severely fatigued (operationalised in different ways) at T1 and T2 and to investigate changes in physical and social functioning, in the number and severity of somatic symptoms and in problems concentrating across T1 and T2.

Discussion

This is the first trial testing a cognitive behavioural intervention targeting severe fatigue after COVID-19. If Fit after COVID is effective in reducing fatigue severity following COVID-19, this intervention could contribute to alleviating the long-term health consequences of COVID-19 by relieving one of its most prevalent and distressing long-term symptoms.

Trial registration

Netherlands Trial Register NL8947. Registered on 14 October 2020.
Managing solar retinopathy with suprachoroidal triamcinolone acetonide injection in a young girl: a case report
Authors: Marashi Ameen , Baba Marwa , Zazo Aya
Published: December 2021

Background

Solar retinopathy is a disease that causes photochemical toxicity in the retinal fovea tissues, leading to an acute decrease of vision.

Case presentation

This case report is an interventional case of an asymptomatic 17-year-old Caucasian female with a history of suddenly decreased vision due to solar retinopathy. The patient was managed with a custom-made needle injection of triamcinolone acetonide in the suprachoroidal space. Four months post suprachoroidal injection showed an anatomical and functional improvement in the ellipsoid zone layer through optical coherence tomography signal reappearance. In addition, the best-corrected visual acuity had improved from 0.1 to 1.0 on the Snellen chart with the disappearance of the scotoma. However, there was a mild increase in intraocular pressure after this procedure, controlled with topical hypertensive eye drops.

Conclusion

Suprachoroidal triamcinolone acetonide injection using a custom-made needle showed both functional and anatomical improvement of macular changes post-solar retinopathy, with acceptable safety outcomes in a young female.
Unacceptable failure of osteochondral glenoid allograft for biologic resurfacing of the glenoid
Authors: Familiari Filippo , Hochreiter Bettina , Gerber Christian
Published: December 2021

Purpose

Glenohumeral osteoarthritis (OA) represents a challenging problem in young, physically active patients. It was the purpose of this investigation to evaluate the results of a pilot study involving glenoid resurfacing with a glenoid allograft combined with a hemiarthroplasty on the humeral side.

Methods

Between April 2011 to November 2013, 5 patients (3 men, 2 women, mean age 46.4, range 35-57) with advanced OA of the glenohumeral joint, were treated with a humeral head replacement combined with replacement of the glenoid surface with an osteochondral, glenoid allograft.

Results

Overall, clinically, there was one excellent, one satisfactory and three poor results. Mean preoperative subjective shoulder value (SSV) was 34% (range: 20-50%) and preoperative relative Constant-Murley-Score (CSr) was 43 points (range: 29-64 points). Three patients with poor results had to be revised within the first three years. Their mean pre-revision SSV and CSr were 38% (range: 15-80%) and 36 points (range: 7-59 points) respectively. One patient was revised 9 years after the primary procedure with advanced glenoid erosion and pain and one patient has an ongoing satisfactory outcome without revision. Their SSVs were 60% and 83%, their CSr were 65 points and 91 points, 9 and 10 years after the primary procedure, respectively. Mean follow-up was 7 years (2-10 years) and mean time to revision was 4 years (range: 1-9 years).

Conclusion

The in-vivo pilot study of a previously established in-vitro technique of osteochondral glenoid allograft combined with humeral HA led to three early failures and only one really satisfactory clinical outcome which, however, was associated with advanced glenoid erosion. Osteochondral allograft glenoid resurfacing was associated with an unacceptable early failure rate and no results superior to those widely documented for HA or TSA, so that the procedure has been abandoned.

Level of evidence

Level IV, Case Series, Treatment Study.
Evaluating underlying causative factors for earthquake-induced landslides and landslide susceptibility mapping in Upper Indrawati Watershed, Nepal
Authors: Gautam Pawan , Kubota Tetsuya , Aditian Aril
Published: December 2021

The main objective of this study is to understand the overall impact of earthquake in upper Indrawati Watershed, located in the high mountainous region of Nepal. Hence, we have assessed the relationship between the co-seismic landslide and underlying causative factors as well as performed landslide susceptibility mapping (LSM) to identify the landslide susceptible zone in the study area. We assessed the landslides distribution in terms of density, number, and area within 85 classes of 13 causal factors including slope, aspect, elevation, formation, land cover, distance to road and river, soil type, total curvature, seismic intensity, topographic wetness index, distance to fault, and flow accumulation. The earthquake-induced landslide is clustered in Northern region of the study area, which is dominated by steep rocky slope, forested land, and low human density. Among the causal factors, 'slope' showed positive correlation for landslide occurrence. Increase in slope in the study area also escalates the landslide distribution, with highest density at 43%, landslide number at 4.34/km2, and landslide area abundance at 2.97% in a slope class (> 50°). We used logistic regression (LR) for LSM integrating with geographic information system. LR analysis depicts that land cover is the best predictor followed by slope and distance to fault with higher positive coefficient values. LSM was validated by assessing the correctly classified landslides under susceptibility categories using area under curve (AUC) and seed cell area index (SCAI). The LSM approach showed good accuracy with respective AUC values for success rate and prediction rate of 0.843 and 0.832. Similarly, the decreasing SCAI value from very low to very high susceptibility categories advise satisfactory accuracy of the LSM approach.
Glycoprotein 2 in health and disease: lifting the veil
Authors: Lin Yingsong , Nakatochi Masahiro , Sasahira Naoki , Ueno Makoto , Egawa Naoto , Adachi Yasushi , Kikuchi Shogo
Published: December 2021

In 2020, we discovered glycoprotein 2 (GP2) variants associated with pancreatic cancer susceptibility in a genome-wide association study involving the Japanese population. Individuals carrying a missense coding variant (rs78193826) in the GP2 gene resulting in a p.V432M substitution had an approximately 1.5-fold higher risk of developing pancreatic cancer than those without this variant. GP2 is expressed on the inner surface of zymogen granules in pancreatic acinar cells, which are responsible for the sorting, storage and secretion of digestive enzymes. Upon neuronal, hormonal, or other stimulation, GP2 is cleaved from the membrane of zymogen granules and then secreted into the pancreatic duct and intestinal lumen. While the functions of GP2 remain poorly understood, emerging evidence suggests that it plays an antibacterial role in the gastrointestinal tract after being secreted from pancreatic acinar cells. Impaired GP2 functions may facilitate the adhesion of bacteria to the intestinal mucosa. In this review article, we summarize the role of GP2 in health and disease, emphasizing its functions in the gastrointestinal tract, as well as genetic variations in the GP2 gene and their associations with disease susceptibility. We hope that its robust genetic associations with pancreatic cancer, coupled with its emerging role in gastrointestinal mucosal immunity, will spur renewed research interest in GP2, which has been understudied over the past 30 years compared with its paralog uromodulin (UMOD).
A comprehensive review of machine learning techniques on diabetes detection
Authors: Sharma Toshita , Shah Manan
Published: December 2021

Diabetes mellitus has been an increasing concern owing to its high morbidity, and the average age of individual affected by of individual affected by this disease has now decreased to mid-twenties. Given the high prevalence, it is necessary to address with this problem effectively. Many researchers and doctors have now developed detection techniques based on artificial intelligence to better approach problems that are missed due to human errors. Data mining techniques with algorithms such as - density-based spatial clustering of applications with noise and ordering points to identify the cluster structure, the use of machine vision systems to learn data on facial images, gain better features for model training, and diagnosis via presentation of iridocyclitis for detection of the disease through iris patterns have been deployed by various practitioners. Machine learning classifiers such as support vector machines, logistic regression, and decision trees, have been comparative discussed various authors. Deep learning models such as artificial neural networks and recurrent neural networks have been considered, with primary focus on long short-term memory and convolutional neural network architectures in comparison with other machine learning models. Various parameters such as the root-mean-square error, mean absolute errors, area under curves, and graphs with varying criteria are commonly used. In this study, challenges pertaining to data inadequacy and model deployment are discussed. The future scope of such methods has also been discussed, and new methods are expected to enhance the performance of existing models, allowing them to attain greater insight into the conditions on which the prevalence of the disease depends.
Pelvic floor rehabilitation in the treatment of mixed urinary incontinence among women
Authors: Elshatby Nehad Mohamed , Imam Mohamed Hassan , Shoukry Mohamed Shafik , Hassan Marwa Mohamed , Saba Emmanuel Kamal Aziz
Published: December 2021

Background

Mixed urinary incontinence (MUI) is a common underreported problem among females; it has a major effect on patients’ quality of life. Treatment may be difficult since a single modality cannot be enough to alleviate both the urge and the stress symptoms. Biofeedback-assisted pelvic floor muscle training (PFMT) has a great role in strengthening the pelvic floor muscles especially when accompanied by electrical stimulation. Neuromodulation is another safe well-tolerated method that may improve symptoms of female voiding dysfunction. There are no previous studies that assessed the efficacy of biofeedback-assisted pelvic floor muscle training versus two different types of peripheral neuromodulation which are transcutaneous posterior tibial nerve stimulation (TPTNS) and anogenital neuromodulation in the treatment of mixed urinary incontinence among women. The aim of this work is to study the effectiveness of biofeedback-assisted pelvic floor muscle training with electrostimulation versus two different methods of peripheral neuromodulation techniques in the treatment of women with MUI. Patients were subjected to history taking, assessment questionnaires (Questionnaire for female Urinary Incontinence Diagnosis (QUID), Australian Pelvic Floor Questionnaire (PFQ), and International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form (ICIQ-UI-SF)), clinical examination, and manometric pressure assessment. The patients were allocated randomly into three groups. Group I received biofeedback-assisted pelvic floor muscle training and faradic electrical stimulation, group II received posterior tibial neuromodulation, and group III received anogenital neuromodulation.

Results

The present study included 68 non-virgin female patients with mixed urinary incontinence. Significant improvement was noticed in the three studied groups on the subjective and objective levels. No statistically significant difference was reported between the studied groups following the different types of intervention.

Conclusions

Biofeedback-assisted pelvic floor muscle training with electrostimulation is as effective as anogenital neuromodulation and posterior tibial neuromodulation in the treatment of mixed urinary incontinence among females.

Trial registration

PACTR, PACTR202107816829078. Registered 29 July 2021 - Retrospectively registered.
Novel Program Offering Remote, Asynchronous Subspecialist Input in Thoracic Oncology: Early Experience and Insights Gained During the COVID-19 Pandemic
Authors: West Howard Jack , Tan Yuan Angela , Barzi Afsaneh , Wong Debra , Parsley Robert , Sachs Todd
Published: December 2021

PURPOSE:

AccessHope is a program developed initially by City of Hope to provide remote subspecialist input on cancer care for patients as a supplemental benefit for specific payers or employers. The leading platform for this work has been an asynchronous model of review of medical records followed by a detailed assessment of past and current management along with discussion of potential future options in a report sent to the local oncologist. This summary describes an early period of development and growth of this service, focusing on cases of lung cancer, particularly during the COVID-19 pandemic.

METHODS:

Cases were primarily identified by a trigger list of cancer diagnoses that included non–small-cell lung cancer and small-cell lung cancer. After medical records were obtained, a summary narrative was provided to a thoracic oncology specialist who wrote a case review sent to the local physician, followed by a direct discussion with the recipient. We focused on feasibility as measured by case volumes, the rates of concordance between the subspecialist reviewer with the local team, and cost savings from recommended changes, using descriptive statistics.

RESULTS:

From April 2019 to November 2020, 110 cases were reviewed: 55% male, median age 62.5 years (range, 33-92 years); 82% non–small-cell lung cancer (12% stage I or II, 16% stage III, and 57% stage IV), and 17% small-cell lung cancer (4% limited and 14% extensive). Median turnaround time for report send-out was 5.0 days. The review agreed with local management in 79 (72%) cases and disagreed in 31 (28%) cases; notably, specific additional recommendations were associated with evidence-based anticipated improvements in efficacy in 76 cases (69%) and improvement in potential for cure in 14 cases (13%). Recommendations leading to cost savings were identified in 14 cases (13%), translating to a projected cost savings of $19,062 (USD) per patient for the entire cohort of patient cases reviewed.

CONCLUSION:

We demonstrate the feasibility of completing a rapid turnaround of cases of lung cancer either patient-initiated for review or prospectively triggered by diagnosis and stage. This program of asynchronous second opinions identified evidence-based management changes affecting current treatment in 28% and potential improvements to improve care in 92% of patients, along with cost savings realized by eliminating low-value interventions.
Novel Transdural Epiarachnoid Approach for Large Central Disk Herniation in Upper Lumbar Spine
Authors: Nishikawa Hirofumi , Fujimoto Masashi , Tanioka Satoru , Ikezawa Munenari , Nakatsuka Yoshinari , Araki Tomohiro , Suzuki Hidenori , Mizuno Masaki
Published: December 2021

BACKGROUND AND IMPORTANCE:

The treatment for large central disk herniation (LCDH) at upper lumbar spine is often challenging. Previous reports showed various surgical strategies, such as microdiscectomy with posterior fixation, endoscopic surgery, and microdiscectomy through transdural approach. However, there is no consensus regarding which surgical option is better for LCDH at upper lumbar spine. In this report, we describe the novel transdural epiarachnoid approach (TDEA), which uses the corridor of epiarachnoid space for microdiscectomy. Compared with classical transdural approaches, this novel approach may reduce risks of postoperative cerebrospinal fluid leakage and the development of arachnoiditis.

CLINICAL PRESENTATION:

A 69-yr-old man presented with progressive bilateral radiating leg pain, intermittent claudication, and low back pain. Magnetic resonance images and computed tomography scans revealed LCDH at L2/3 level. We performed microdiscectomy using the TDEA. Postoperative course was uneventful, and his symptoms were relieved after surgery.

CONCLUSION:

The novel TDEA for LCDH at upper lumbar spine is illustrated with a video. This novel approach has an advantage of the preservation of subarachnoid components compared with classical transdural approaches.
Multiple neural bHLHs ensure the precision of a neuronal specification event in Caenorhabditis elegans
Authors: Filippopoulou Konstantina , Couillault Carole , Bertrand Vincent
Published: December 2021

Neural bHLH transcription factors play a key role in the early steps of neuronal specification in many animals. We have previously observed that the Achaete-Scute HLH-3, the Olig HLH-16 and their binding partner the E-protein HLH-2 activate the terminal differentiation program of a specific class of cholinergic neurons, AIY, in Caenorhabditis elegans. Here we identify a role for a fourth bHLH, the Neurogenin NGN-1, in this process, raising the question of why so many neural bHLHs are required for a single neuronal specification event. Using quantitative imaging we show that the combined action of different bHLHs is needed to activate the correct level of expression of the terminal selector transcription factors TTX-3 and CEH-10 that subsequently initiate and maintain the expression of a large battery of terminal differentiation genes. Surprisingly, the different bHLHs have an antagonistic effect on another target, the proapoptotic BH3-only factor EGL-1, normally not expressed in AIY and otherwise detrimental for its specification. We propose that the use of multiple neural bHLHs allows robust neuronal specification while, at the same time, preventing spurious activation of deleterious genes.
Smaug1 membrane-less organelles respond to AMPK and mTOR and affect mitochondrial function
Authors: Fernández-Alvarez Ana J. , Gabriela Thomas María , Pascual Malena L. , Habif Martín , Pimentel Jerónimo , Corbat Agustín A. , Pessoa João P. , La Spina Pablo E. , Boscaglia Lara , Plessis Anne , Carmo-Fonseca Maria , Grecco Hernán E. , Casado Marta , Boccaccio Graciela L.
Published: December 2021

Smaug is a conserved translational regulator that binds numerous mRNAs, including nuclear transcripts that encode mitochondrial enzymes. Smaug orthologs form cytosolic membrane-less organelles (MLOs) in several organisms and cell types. We have performed single-molecule fluorescence in situ hybridization (FISH) assays that revealed that SDHB and UQCRC1 mRNAs associate with Smaug1 bodies in U2OS cells. Loss of function of Smaug1 and Smaug2 (also known as SAMD4A and SAMD4B, respectively) affected both mitochondrial respiration and morphology of the mitochondrial network. Phenotype rescue by Smaug1 transfection depends on the presence of its RNA-binding domain. Moreover, we identified specific Smaug1 domains involved in MLO formation, and found that impaired Smaug1 MLO condensation correlates with mitochondrial defects. Mitochondrial complex I inhibition upon exposure to rotenone, but not strong mitochondrial uncoupling upon exposure to CCCP, rapidly induced the dissolution of Smaug1 MLOs. Metformin and rapamycin elicited similar effects, which were blocked by pharmacological inhibition of AMP-activated protein kinase (AMPK). Finally, we found that Smaug1 MLO dissolution weakens the interaction with target mRNAs, thus enabling their release. We propose that mitochondrial respiration and the AMPK–mTOR balance controls the condensation and dissolution of Smaug1 MLOs, thus regulating nuclear mRNAs that encode key mitochondrial proteins.

This article has an associated First Person interview with the first authors of the paper.
Mechanisms Responsible for Adsorption of Molybdate ions on Alumina for the Production of Medical Radioisotopes
Authors: Fujita Yoshitaka , Niizeki Tomotake , Fukumitsu Nobuyoshi , Ariga Katsuhiko , Yamauchi Yusuke , Malgras Victor , Kaneti Yusuf Valentino , Liu Chia-Hung , Hatano Kentaro , Suematsu Hisayuki , Suzuki Tatsuya , Tsuchiya Kunihiko
Published: December 2021

In this work, the mechanisms responsible for the adsorption of molybdate ions on alumina are investigated using in-depth surface analyses of alumina specimens immersed in solutions containing different molybdate ions at different pH values. The obtained results reveal that when alumina is immersed in an acidic solution containing molybdate ions, the hydroxyl groups present on the surface are removed to generate positively charged sites, and molybdate ions (MoO42− or AlMo6O24H63−) are adsorbed via an electrostatic interaction. Alumina dissolves slightly in an acidic solution to form AlMo6O24H63−, which is more easily desorbed than MoO42−. Furthermore, the enhancement in the Mo adsorption or desorption property may be achieved by enriching the surface of the alumina adsorbent with many –OH groups and optimizing Mo solution to adsorb molybdate ions on alumina as MoO42− ions. These findings will assist researchers in engineering more efficient and stable alumina-based adsorbents for molybdenum adsorption used in medical radioisotope (99Mo/99mTc) generators.
Toward the Synthesis of a Belt-Shaped Cyclic π-Conjugated System Comprising para-Phenylene Framework and Amide Bridging Unit
Authors: Takagi Koji , Miyamoto Daiki , Yamaguchi Hinako , Azumaya Isao
Published: December 2021

Belt-shaped π-conjugated systems have been attracting more and more attention in recent years from the synthetic interest as well as their mysterious properties that linear counterparts do not have. In this paper, the stepwise condensation of 2-bromo-4-(octylamino)benzoic acid and subsequent macrocyclization was carried out to obtain a cyclic hexamer (c6mer). The palladium-catalyzed direct arylation was then performed to get the target belt-shaped molecule (b6mer) although the isolation of b6mer did not meet with success because of the contamination of structural defects. Theoretical calculation of b6mer indicated the strain energy of ca. 100.9 kcal·mol−1 and revealed the electronic transition from degenerate HOMO-1 and HOMO-2 orbitals to LUMO similar to that of parent cycloparaphenylene derivatives.
Opportunistic diagnosis of osteoporotic vertebral fractures on standard imaging performed for alternative indications
Authors: Davy Shane W. , Bergin Diane
Published: December 2021

Osteoporotic vertebral fractures (VFs) are the most common type of osteoporotic fracture. Patients with VF are at increased risk of hip fractures or additional VFs, both of which contribute to patient morbidity and mortality. Early diagnosis of VFs is essential so patients can be prescribed appropriate medical therapy.

Most patients with clinical suspicion for VF have an X-ray of the spine. Many VFs are invisible on X-ray and require further imaging. CT can provide excellent bony detail but uses high doses of ionising radiation. MRI provides excellent soft tissue detail and can distinguish old from new fractures in addition to differentiating osteoporotic VFs from other causes of back pain. Bone scans have a limited role due to poor specificity.

The literature suggests that radiologists frequently miss or do not report VFs when imaging is requested for an alternative clinical indication and when there is no clinical suspicion of VF. Common examples include failure to identify VFs on lateral chest X-rays, sagittal reformats of CT thorax and abdomen, lateral localizers on MRI and scout views on CT.

Failure to diagnose a VF is a missed opportunity to improve management of osteoporosis and reduce risk of further fractures. This article discusses the role of radiographs, CT, MRI and bone scintigraphy in the assessment and recognition of osteoporotic fractures. This article focuses on opportunistic diagnosis of VFs on imaging studies that are performed for other clinical indications. It does not discuss use of dual energy X-ray absorptiometry which is a specific imaging modality for osteoporosis.
Case Report: A Case of Encephalopathy Presenting the Lentiform Fork Sign on MRI in a Diabetic Dialysis Patient
Authors: Ishizaki Yuri , Nishizono Ryuzoh , Kikuchi Masao , Inagaki Hiroko , Sato Yuji , Fujimoto Shouichi
Published: December 2021

Basal ganglia lesions showing an expansile high signal intensity on T2-weighted MRI are termed the lentiform fork sign. This specific finding is mainly observed in diabetic patients with uremic encephalopathy with metabolic acidosis, although there are also reports in patients with ketoacidosis, dialysis disequilibrium syndrome, intoxication, and following drug treatment (e.g., metformin). A 57-year-old Japanese man on chronic hemodialysis for 4 years because of diabetic nephropathy was admitted to our hospital for relatively rapid-onset gait disturbance, severe dysarthria, and consciousness disturbance. Brain T2-weighted MRI showed the lentiform fork sign. Hemodialysis was performed the day before admission, and laboratory tests showed mild metabolic (lactic) acidosis, but no uremia. Surprisingly, metformin, which is contraindicated for patients with end-stage kidney disease, had been prescribed for 6 months in his medication record, and his sluggish speaking and dysarthria appeared gradually after metformin treatment was started. Thus, the encephalopathy was considered to be related to metformin treatment. He received hemodialysis treatment for 6 consecutive days, and his consciousness disturbance and dysarthria improved in 1 week. At the 8-month follow-up, the size of the hyperintensity area on MRI had decreased, while the mild gait disturbance remained. Considering the rapid onset of gait and consciousness disturbance immediately before admission, diabetic uremic syndrome may also have occurred with metformin-related encephalopathy, and resulted in the lentiform fork sign, despite the patient showing no evidence of severe uremia on laboratory data.
Active compound test: ethanolic extract of White Oyster Mushroom (Pleurotus ostreatus) Using HPLC and LC-MS
Authors: Bhekti Rahimah Santun , Firmansyah Agung , Maharani Winni , Andriane Yuke , Santosa Dicky , Romadhona Nurul
Published: December 2021

Background: The use of herbs as traditional medicine in Indonesia is increasing, with more than 40% of Indonesia's population utilizing them. White oyster mushroom (Pleurotus Ostreatus) is a fungus that has various therapeutic effects including antioxidant, anti-inflammatory, anti-bacterial, anti-cholesterol, and anti-cancer properties. This mushroom contains many active substances in its secondary metabolites which have pharmacological effects. The purpose of this study was to identify the active compounds in the ethanolic extract of white oyster mushroom that will form the extract profile and become the basis for drug development.

Methods: The active compound test used High-Performance Liquid Chromatography (HPLC) and Liquid Chromatography with Mass Spectrometer (LC-MS). Ethanolic extract of white oyster mushroom was processed by 70% alcohol maceration, evaporation, and thickening.

Results: The results of the HPLC test showed that the ethanolic extract of white oyster mushroom contained cinnamic acid and rutin, while the LC-MS test showed the presence of p-coumaric acid, Ascorbic acid, Linoleic acid, 9-Eicosene (E), Niacinamide, Veritric acid, Syringic acid, Ergosterol.

Conclusions: The active compounds that were detected in the ethanolic extract of white oyster mushroom showed that the extract had the potential for antioxidant and anti-inflammatory activity.
Long-Haul Vehicle Routing and Scheduling with Biomathematical Fatigue Constraints
Authors: Fu Jiawei , Ma Liang
Published: December 2021

Hours of service (HOS) regulations are among the conventional safety constraints that are compiled by long-haul truck drivers. These regulations have been considered in models and algorithms of vehicle routing problems to assign safe schedules to drivers. However, the HOS regulations neglect a few crucial fatigue risk factors and, at times, fail to generate fatigue-reducing schedules. In this study, a set of biomathematical fatigue constraints (BFCs) derived from biomathematical models are considered for a long-haul vehicle routing and scheduling problem. A BFC scheduling algorithm and a BFC-HOS scheduling algorithm have been developed and then embedded within a tabu search heuristic to solve the combined vehicle routing and scheduling problem. All the solution methods have been tested on modified Solomon instances and a real-life instance, and the computational results confirm the advantages of employing a sophisticated and fatigue-reducing scheduling procedure when planning long-haul transportation.