bluuebunny/crossref_metadata_2025 huggingface dataset:
Abdominal pain due to the spinothalamic tract injury in patients with mild traumatic brain injury: a case report
Authors: Jang Sung Ho , Kwon Young Hyeon , Lee Sung Jun
Published: April 2020

Background

We report on a patient with a mild traumatic brain injury (TBI) who developed abdominal pain due to spinothalamic tract (STT) injuries revealed by diffusion tensor tractography (DTT).

Case presentation

A 53-year-old female patient suffered head trauma resulting from a backward fall. While bathing at a public bathhouse, she fell backward and struck the occipital area of her head against the floor. After the head trauma, she experienced pain in the abdomen and in both hands and feet. She underwent evaluations including conventional brain MRI, abdominal and pelvic ultrasonography, and stomach and intestine endoscopy. No abnormality was observed in her brain or abdomen. In addition, her abdominal pain had not been relieved by medical management. When she came to our hospital 4 years after the head trauma, her pain characteristics and severity were as follows: intermittent pain without allodynia or hyperalgesia; squeezing and warm creeping-like pain in the abdomen (visual analog scale score: 7); tingling pain in both hands and feet (visual analog scale score: 7). She was prescribed pregabalin and gabapentin, and her abdominal and limb pain was well-controlled at a tolerable level. On DTT 4 years after head trauma, the upper portion of the spinothalamic tracts (STTs) in both hemispheres showed partial tearing.

Discussion and conclusions

Injury of the STT was demonstrated by using DTT in a patient who showed abdominal pain that was refractory to medical management following mild TBI. Our results suggest that central pain due to STT injury might be suspected in patients with abdominal pain that is refractory to medical management following TBI.
Sedentary behavior patterns and adiposity in children: a study based on compositional data analysis
Authors: Gába Aleš , Pedišić Željko , Štefelová Nikola , Dygrýn Jan , Hron Karel , Dumuid Dorothea , Tremblay Mark
Published: April 2020

Background

Between-person differences in sedentary patterns should be considered to understand the role of sedentary behavior (SB) in the development of childhood obesity. This study took a novel approach based on compositional data analysis to examine associations between SB patterns and adiposity and investigate differences in adiposity associated with time reallocation between time spent in sedentary bouts of different duration and physical activity.

Methods

An analysis of cross-sectional data was performed in 425 children aged 7–12 years (58% girls). Waking behaviors were assessed using ActiGraph GT3X accelerometer for seven consecutive days. Multi-frequency bioimpedance measurement was used to determine adiposity. Compositional regression models with robust estimators were used to analyze associations between sedentary patterns and adiposity markers. To examine differences in adiposity associated with time reallocation, we used the compositional isotemporal substitution model.

Results

Significantly higher fat mass percentage (FM%;βilr1 = 0.18; 95% CI: 0.01, 0.34;p = 0.040) and visceral adipose tissue (VAT;βilr1 = 0.37; 95% CI: 0.03, 0.71;p = 0.034) were associated with time spent in middle sedentary bouts in duration of 10–29 min (relative to remaining behaviors). No significant associations were found for short (< 10 min) and long sedentary bouts (≥30 min). Substituting the time spent in total SB with moderate-to-vigorous physical activity (MVPA) was associated with a decrease in VAT. Substituting 1 h/week of the time spent in middle sedentary bouts with MVPA was associated with 2.9% (95% CI: 1.2, 4.6), 3.4% (95% CI: 1.2, 5.5), and 6.1% (95% CI: 2.9, 9.2) lower FM%, fat mass index, and VAT, respectively. Moreover, substituting 2 h/week of time spent in middle sedentary bouts with short sedentary bouts was associated with 3.5% (95% CI: 0.02, 6.9) lower FM%.

Conclusions

Our findings suggest that adiposity status could be improved by increasing MVPA at the expense of time spent in middle sedentary bouts. Some benefits to adiposity may also be expected from replacing middle sedentary bouts with short sedentary bouts, that is, by taking standing or activity breaks more often. These findings may help design more effective interventions to prevent and control childhood obesity.
Case report of sigmoid colon perforation and colocutaneous fistula due to retropubic midurethral sling placement for stress urinary incontinence
Authors: Huang Xiao , Jiang Hai , Xie Liping
Published: April 2020

Background

Sigmoid bowel perforation is a very rare and serious complication of the retropubic tension-free vaginal tape (TVT) procedure for female stress urinary incontinence. The complication can be avoided with the use of the correct manipulation technique.

Case presentation

A 75-year-old female patient underwent a retropubic TVT procedure in the local hospital for the treatment of stress urinary incontinence. The procedure was smooth. Two weeks after surgery, the patient began to complain of fever and bloody, purulent discharge from the left suprapubic skin wound. During a 4-month period after surgery, she was admitted to the local hospital 4 times for similar infection symptoms. The infections were temporarily controlled with antibiotic administration. The reason for the refractory infection of the left suprapubic skin wound was not identified until a foreign TVT mesh was found in the sigmoid colon via a colonoscopy. We diagnosed that the TVT mesh caused a sigmoid colon perforation that led to colocutaneous fistula. An exploratory laparotomy revealed that the TVT tape perforated into and out of the sigmoid colon. An 8-cm long left part of mesh was removed. Two ruptures of sigmoid colon were mended without the need for bowel resection. At the 4-years follow-up after laparotomy, the patient was doing well and still continent.

Conclusions

Urologists and gynecologists should be aware of the possibility of colon bowel injury in SUI patients with prior sling surgeries. Patient having recurrent suprapubic cutaneous infection may have high degree of suspicion of colon injury after TVT sling. The passage of the retropubic space procedure should be slow and always along the pubic bone according to the anatomy.
A mixed methods investigation of end-of-life surrogate decisions among older adults
Authors: Batteux Eleonore , Ferguson Eamonn , Tunney Richard J.
Published: April 2020

Background

A large number of end-of-life decisions are made by a next-of-kin for a patient who has lost their decision-making capacity. This has given rise to investigations into how surrogates make these decisions. The experimental perspective has focused on examining how the decisions we make for others differ from our own, whereas the qualitative perspective has explored surrogate insights into making these decisions.

Methods

We conducted a mixed methods study to bring these two perspectives together. This is crucial to comparing decision outcomes to the decision process. We asked older adult partners to make end-of-life decisions for each other. They then took part in a semi-structured interview about their decision process. Transcripts were analysed using thematic analysis.

Results

24 participants took part in the study. Surrogates were more likely to take a life-saving treatment at the risk of a diminished quality of life for their partner than for themselves. This was consistent with their transcripts which showed that they wanted to give their partner a better chance of living. Although there was evidence of surrogate inaccuracy in the decision task, participants overwhelmingly reported their intention to make a decision which aligns with the substituted judgment standard. However, uncertainty about their wishes pushed them to consider other factors.

Conclusions

Taking a mixed methods approach allowed us to make novel comparisons between decision outcome and process. We found that the intentions of surrogates broadly align with the expectations of the substituted judgment standard and that previous discussions with their partner helps them to make a decision.
A novel protein encoded by circFNDC3B inhibits tumor progression and EMT through regulating Snail in colon cancer
Authors: Pan Zihao , Cai Jianye , Lin Jiatong , Zhou Huinian , Peng Jingwen , Liang Jinliang , Xia Long , Yin Qi , Zou Baojia , Zheng Jun , Qiao Liang , Zhang Lei
Published: April 2020

Background

Colon cancer (CC) is a common malignant cancer. Recently, circFNDC3B was found to exert biological function in multiple cancers. However, it was unclear whether the potential protein encoded by circFNDC3B is involved in carcinogenesis of CC.

Methods

We used Sanger sequence and RNase R digestion assay to confirm the existence of circFNDC3B, and quantitative real-time PCR was used to evaluate the circRNA’s expression. Then fluorescence in situ hybridization (FISH) was performed to study location of circFNDC3B. The identification of protein encoded by circFNDC3B was performed using LC-MS/MS. The function of circFNDC3B-218aa on proliferation, invasion and migration were assessed by CCK8 assays, colony formation assays, transwell assays, wound-healing assays and animal experiments. RNA-sequencing and western blot were used to identify the gene regulated by circFNDC3B-218aa. Finally, glucose metabolism-related assays were performed to further investigate function of circFNDC3B-218aa.

Results

CircFNDC3B was localized mostly in the cytoplasm, and was decreased in CC cell lines and tissues. The patients with low circFNDC3B expression had a shorter OS (P = 0.0014) than patients with high expression. Moreover, circFNDC3B inhibited the proliferation, invasion and migration of CC cells. Next, we identified that circFNDC3B could encode a novel protein circFNDC3B-218aa. Furthermore, circFNDC3B-218aa, not circFNDC3B, inhibited the proliferation, invasion and migration of CC. Additionally, the in vivo experiments implied that up-regulated circFNDC3B-218aa exhibited an inhibitory effect on CC progression. By RNA-sequencing, western blot and glucose metabolism-related assays, we found that circFNDC3B-218aa inhibited the expression of Snail, and subsequently promoted the tumor-suppressive effect of FBP1 in CC.

Conclusions

The novel circFNDC3B-218aa may serve as a tumor suppressive factor and potential biomarker which may supply the potential therapeutic target for CC.
Comparison and development of machine learning tools for the prediction of chronic obstructive pulmonary disease in the Chinese population
Authors: Ma Xia , Wu Yanping , Zhang Ling , Yuan Weilan , Yan Li , Fan Sha , Lian Yunzhi , Zhu Xia , Gao Junhui , Zhao Jiangman , Zhang Ping , Tang Hui , Jia Weihua
Published: April 2020

Background

Chronic obstructive pulmonary disease (COPD) is a major public health problem and cause of mortality worldwide. However, COPD in the early stage is usually not recognized and diagnosed. It is necessary to establish a risk model to predict COPD development.

Methods

A total of 441 COPD patients and 192 control subjects were recruited, and 101 single-nucleotide polymorphisms (SNPs) were determined using the MassArray assay. With 5 clinical features as well as SNPs, 6 predictive models were established and evaluated in the training set and test set by the confusion matrix AU-ROC, AU-PRC, sensitivity (recall), specificity, accuracy, F1 score, MCC, PPV (precision) and NPV. The selected features were ranked.

Results

Nine SNPs were significantly associated with COPD. Among them, 6 SNPs (rs1007052, OR = 1.671,P = 0.010; rs2910164, OR = 1.416,P < 0.037; rs473892, OR = 1.473,P < 0.044; rs161976, OR = 1.594,P < 0.044; rs159497, OR = 1.445,P < 0.045; and rs9296092, OR = 1.832,P < 0.045) were risk factors for COPD, while 3 SNPs (rs8192288, OR = 0.593,P < 0.015; rs20541, OR = 0.669,P < 0.018; and rs12922394, OR = 0.651,P < 0.022) were protective factors for COPD development. In the training set, KNN, LR, SVM, DT and XGboost obtained AU-ROC values above 0.82 and AU-PRC values above 0.92. Among these models, XGboost obtained the highest AU-ROC (0.94), AU-PRC (0.97), accuracy (0.91), precision (0.95), F1 score (0.94), MCC (0.77) and specificity (0.85), while MLP obtained the highest sensitivity (recall) (0.99) and NPV (0.87). In the validation set, KNN, LR and XGboost obtained AU-ROC and AU-PRC values above 0.80 and 0.85, respectively. KNN had the highest precision (0.82), both KNN and LR obtained the same highest accuracy (0.81), and KNN and LR had the same highest F1 score (0.86). Both DT and MLP obtained sensitivity (recall) and NPV values above 0.94 and 0.84, respectively. In the feature importance analyses, we identified that AQCI, age, and BMI had the greatest impact on the predictive abilities of the models, while SNPs, sex and smoking were less important.

Conclusions

The KNN, LR and XGboost models showed excellent overall predictive power, and the use of machine learning tools combining both clinical and SNP features was suitable for predicting the risk of COPD development.
Microglial physiological properties and interactions with synapses are altered at presymptomatic stages in a mouse model of Huntington’s disease pathology
Authors: Savage Julie C. , St-Pierre Marie-Kim , Carrier Micaël , El Hajj Hassan , Novak Sammy Weiser , Sanchez Maria Gabriela , Cicchetti Francesca , Tremblay Marie-Ève
Published: April 2020

Background

Huntington’s disease (HD) is a dominantly inherited neurodegenerative disorder that affects cognitive and motor abilities by primarily targeting the striatum and cerebral cortex. HD is caused by a mutation elongating the CAG repeats within the Huntingtin gene, resulting in HTT protein misfolding. Although the genetic cause of HD has been established, the specific susceptibility of neurons within various brain structures has remained elusive. Microglia, which are the brain’s resident macrophages, have emerged as important players in neurodegeneration. Nevertheless, few studies have examined their implication in HD.

Methods

To provide novel insights, we investigated the maturation and dysfunction of striatal microglia using the R6/2 mouse model of HD. This transgenic model, which presents with 120+/-5 CAG repeats, displays progressive motor deficits beginning at 6 weeks of age, with full incapacitation by 13 weeks. We studied microglial morphology, phagocytic capacity, and synaptic contacts in the striatum of R6/2 versus wild-type (WT) littermates at 3, 10, and 13 weeks of age, using a combination of light and transmission electron microscopy. We also reconstructed dendrites and determined synaptic density within the striatum of R6/2 and WT littermates, at nanoscale resolution using focused ion beam scanning electron microscopy.

Results

At 3 weeks of age, prior to any known motor deficits, microglia in R6/2 animals displayed a more mature morphological phenotype than WT animals. Microglia from R6/2 mice across all ages also demonstrated increased phagocytosis, as revealed by light microscopy and transmission electron microscopy. Furthermore, microglial processes from 10-week-old R6/2 mice made fewer contacts with synaptic structures than microglial processes in 3-week-old R6/2 mice and age-matched WT littermates. Synaptic density was not affected by genotype at 3 weeks of age but increased with maturation in WT mice. The location of synapses was lastly modified in R6/2 mice compared with WT controls, from targeting dendritic spines to dendritic trunks at both 3 and 10 weeks of age.

Conclusions

These findings suggest that microglia may play an intimate role in synaptic alteration and loss during HD pathogenesis.
Correction to: Identifying the active components of Baihe–Zhimu decoction that ameliorate depressive disease by an effective integrated strategy: a systemic pharmacokinetics study combined with classical depression model tests
Authors: Zhong Ming , Tian Xiaoting , Chen Shuoji , Chen Mingcang , Guo Ziqiong , Zhang Minna , Zheng Gongpu , Li Zhixiong , Shi Zhangpeng , Wang Guanghui , Gao Honggang , Liu Fang , Huang Chenggang
Published: April 2020

In the original publication of this article [1], another affiliation (Affiliation 3: University of Chinese Academy of Sciences, Beijing 100049, People’s Republic of China.) for the author Ziqiong Guo is missing due to the carelessness during the author proof. In addition, in Affiliation 2 “Chinese Academy of Science” should be changed to “Chinese Academy of Sciences”.
Machine learning and clinical epigenetics: a review of challenges for diagnosis and classification
Authors: Rauschert S. , Raubenheimer K. , Melton P. E. , Huang R. C.
Published: April 2020

Background

Machine learning is a sub-field of artificial intelligence, which utilises large data sets to make predictions for future events. Although most algorithms used in machine learning were developed as far back as the 1950s, the advent of big data in combination with dramatically increased computing power has spurred renewed interest in this technology over the last two decades.

Main body

Within the medical field, machine learning is promising in the development of assistive clinical tools for detection of e.g. cancers and prediction of disease. Recent advances in deep learning technologies, a sub-discipline of machine learning that requires less user input but more data and processing power, has provided even greater promise in assisting physicians to achieve accurate diagnoses.

Within the fields of genetics and its sub-field epigenetics, both prime examples of complex data, machine learning methods are on the rise, as the field of personalised medicine is aiming for treatment of the individual based on their genetic and epigenetic profiles.

Conclusion

We now have an ever-growing number of reported epigenetic alterations in disease, and this offers a chance to increase sensitivity and specificity of future diagnostics and therapies. Currently, there are limited studies using machine learning applied to epigenetics. They pertain to a wide variety of disease states and have used mostly supervised machine learning methods.
Innovation in the public sector in a small open economy-initial investigation of patent activity at the Czech universities
Authors: Maresova Petra , Soukal Ivan , Stemberkova Ruzena , Kuca Kamil
Published: April 2020

For a successful economy, the interaction between research and its application in practice plays a key role. The aim of this paper is to analyze the institutional factors of patent activity at universities in the Czech Republic. The following five factors were selected for detailed investigation: budget from government, number of employees: professors, associate professor, and assistant professor, number of researchers and other employees, number of students (PhD, master, and bachelor), technology transfer workers. The patent activity analysis used methods of retrospective data analysis in the field of R&D activities, unstructured interviews, and statistical data processing. Following from the basic characteristics of the collected data, patent activity is related to the nature of universities, where technical universities are in leading positions in the monitored period of industrial-legal protection. However, the importance of encouraging innovation activity across all disciplines is crucial. The result of monitoring the dependency shows that a relationship of efficiencies and patent output is influenced by the size of a university. Secondly, there can be observed that technology transfer efficiency contributes more to the patent output that research staff efficiency.
Current understanding of metal ions in the pathogenesis of Alzheimer’s disease
Authors: Wang Lu , Yin Ya-Ling , Liu Xin-Zi , Shen Peng , Zheng Yan-Ge , Lan Xin-Rui , Lu Cheng-Biao , Wang Jian-Zhi
Published: April 2020

Background

The homeostasis of metal ions, such as iron, copper, zinc and calcium, in the brain is crucial for maintaining normal physiological functions. Studies have shown that imbalance of these metal ions in the brain is closely related to the onset and progression of Alzheimer’s disease (AD), the most common neurodegenerative disorder in the elderly.

Main body

Erroneous deposition/distribution of the metal ions in different brain regions induces oxidative stress. The metal ions imbalance and oxidative stress together or independently promote amyloid-β (Aβ) overproduction by activating β- or γ-secretases and inhibiting α-secretase, it also causes tau hyperphosphorylation by activating protein kinases, such as glycogen synthase kinase-3β (GSK-3β), cyclin-dependent protein kinase-5 (CDK5), mitogen-activated protein kinases (MAPKs), etc., and inhibiting protein phosphatase 2A (PP2A). The metal ions imbalances can also directly or indirectly disrupt organelles, causing endoplasmic reticulum (ER) stress; mitochondrial and autophagic dysfunctions, which can cause or aggravate Aβ and tau aggregation/accumulation, and impair synaptic functions. Even worse, the metal ions imbalance-induced alterations can reversely exacerbate metal ions misdistribution and deposition. The vicious cycles between metal ions imbalances and Aβ/tau abnormalities will eventually lead to a chronic neurodegeneration and cognitive deficits, such as seen in AD patients.

Conclusion

The metal ions imbalance induces Aβ and tau pathologies by directly or indirectly affecting multiple cellular/subcellular pathways, and the disrupted homeostasis can reversely aggravate the abnormalities of metal ions transportation/deposition. Therefore, adjusting metal balance by supplementing or chelating the metal ions may be potential in ameliorating AD pathologies, which provides new research directions for AD treatment.
Inference-based accuracy of metagenome prediction tools varies across sample types and functional categories
Authors: Sun Shan , Jones Roshonda B. , Fodor Anthony A.
Published: April 2020

Background

Despite recent decreases in the cost of sequencing, shotgun metagenome sequencing remains more expensive compared with 16S rRNA amplicon sequencing. Methods have been developed to predict the functional profiles of microbial communities based on their taxonomic composition. In this study, we evaluated the performance of three commonly used metagenome prediction tools (PICRUSt, PICRUSt2, and Tax4Fun) by comparing the significance of the differential abundance of predicted functional gene profiles to those from shotgun metagenome sequencing across different environments.

Results

We selected 7 datasets of human, non-human animal, and environmental (soil) samples that have publicly available 16S rRNA and shotgun metagenome sequences. As we would expect based on previous literature, strong Spearman correlations were observed between predicted gene compositions and gene relative abundance measured with shotgun metagenome sequencing. However, these strong correlations were preserved even when the abundance of genes were permuted across samples. This suggests that simple correlation coefficient is a highly unreliable measure for the performance of metagenome prediction tools. As an alternative, we compared the performance of genes predicted with PICRUSt, PICRUSt2, and Tax4Fun to sequenced metagenome genes in inference models associated with metadata within each dataset. With this approach, we found reasonable performance for human datasets, with the metagenome prediction tools performing better for inference on genes related to “housekeeping” functions. However, their performance degraded sharply outside of human datasets when used for inference.

Conclusion

We conclude that the utility of PICRUSt, PICRUSt2, and Tax4Fun for inference with the default database is likely limited outside of human samples and that development of tools for gene prediction specific to different non-human and environmental samples is warranted.
PRIMAGE project: predictive in silico multiscale analytics to support childhood cancer personalised evaluation empowered by imaging biomarkers
Authors: Martí-Bonmatí Luis , Alberich-Bayarri Ángel , Ladenstein Ruth , Blanquer Ignacio , Segrelles J. Damian , Cerdá-Alberich Leonor , Gkontra Polyxeni , Hero Barbara , García-Aznar J. M. , Keim Daniel , Jentner Wolfgang , Seymour Karine , Jiménez-Pastor Ana , González-Valverde Ismael , Martínez de las Heras Blanca , Essiaf Samira , Walker Dawn , Rochette Michel , Bubak Marian , Mestres Jordi , Viceconti Marco , Martí-Besa Gracia , Cañete Adela , Richmond Paul , Wertheim Kenneth Y. , Gubala Tomasz , Kasztelnik Marek , Meizner Jan , Nowakowski Piotr , Gilpérez Salvador , Suárez Amelia , Aznar Mario , Restante Giuliana , Neri Emanuele
Published: April 2020

PRIMAGE is one of the largest and more ambitious research projects dealing with medical imaging, artificial intelligence and cancer treatment in children. It is a 4-year European Commission-financed project that has 16 European partners in the consortium, including the European Society for Paediatric Oncology, two imaging biobanks, and three prominent European paediatric oncology units. The project is constructed as an observational in silico study involving high-quality anonymised datasets (imaging, clinical, molecular, and genetics) for the training and validation of machine learning and multiscale algorithms. The open cloud-based platform will offer precise clinical assistance for phenotyping (diagnosis), treatment allocation (prediction), and patient endpoints (prognosis), based on the use of imaging biomarkers, tumour growth simulation, advanced visualisation of confidence scores, and machine-learning approaches. The decision support prototype will be constructed and validated on two paediatric cancers: neuroblastoma and diffuse intrinsic pontine glioma. External validation will be performed on data recruited from independent collaborative centres. Final results will be available for the scientific community at the end of the project, and ready for translation to other malignant solid tumours.
Decrease of 14–3-3 proteins by glutamate exposure in the cerebral cortex of newborn rats
Authors: Kang Ju-Bin , Lee Seung-Yun , Park Dong-Ju , Koh Phil-Ok
Published: April 2020

Glutamate is a representative excitatory neurotransmitter. However, excessive glutamate exposure causes neuronal cell damage by generating neuronal excitotoxicity. Excitotoxicity in neonates caused by glutamate treatment induces neurological deficits in adults. The 14–3-3 family proteins are conserved proteins that are expressed ubiquitously in a variety of tissues. These proteins contribute to cellular processes, including signal transduction, protein synthesis, and cell cycle control. We proposed that glutamate induces neuronal cell damage by regulating 14–3-3 protein expression in newborn animals. In this study, we investigated the histopathological changes and 14–3-3 proteins expressions as a result of glutamate exposure in the neonatal cerebral cortex. Rat pups at post-natal day 7 were intraperitoneally administrated with vehicle or glutamate (10 mg/kg). Animals were sacrificed 4 h after treatment, and brain tissues were fixed for histological study. Cerebral cortices were isolated and frozen for proteomic study. We observed serious histopathological damages including shrunken dendrites and atypical neurons in glutamate-treated cerebral cortices. In addition, we identified that 14–3-3 family proteins decreased in glutamate-exposed cerebral cortices using a proteomic approach. Moreover, Western blot analysis provided results that glutamate treatment in neonates decreased 14–3-3 family proteins expressions, including the β/α, ζ/δ, γ, ε, τ, and η isoforms. 14–3-3 proteins are involved in signal transduction, metabolism, and anti-apoptotic functions. Thus, our findings suggest that glutamate induces neonatal neuronal cell damage by modulating 14–3-3 protein expression.
Current Perspectives on Therapy for Chronic Lymphocytic Leukemia
Authors: Awan Farrukh T. , Al-Sawaf Othman , Fischer Kirsten , Woyach Jennifer A.
Published: April 2020

Therapy for chronic lymphocytic leukemia has improved dramatically over the past decade with the introduction of new targeted therapies and a paradigm shift toward targeted therapies for the majority of patients. Better understanding of prognostic factors has helped tailor therapy for individual patients, and work continues to identify optimal therapy for each patient. When therapy is required, most patients will be treated with targeted therapies, either the Bruton tyrosine kinase (BTK) inhibitors ibrutinib or acalabrutinib or the BCL-2 inhibitor venetoclax in combination with obinutuzumab. Without head-to-head comparisons showing differential efficacy among these options, considerations regarding safety, patient preference, and ability to sequence therapy currently influence treatment decisions. Also, clinical trials investigating combinations of these therapies have the potential to further change the standard of care. In this review, we cover the currently available options for the frontline treatment of chronic lymphocytic leukemia (CLL) and discuss safety considerations and toxicity management with each agent as well as novel combination strategies currently under investigation.
Successful Strategies to Address Disparities: Insurer and Employer Perspectives
Authors: Patel Manali I. , Snyder Richard , Brawley Otis
Published: April 2020

Disparities in cancer have been documented for decades and continue to persist despite clinical advancements in cancer prevention, detection, and treatment. Disparate cancer outcomes continue to affect many populations in the United States and globally, including racial and ethnic minorities, populations with low income and education, and residents of rural areas or low socioeconomic neighborhoods, among others. Addressing cancer disparities requires approaches that are multilevel. Addressing social determinants of health, such as removing obstacles to health (e.g., poverty, discrimination, access to housing and education, jobs with fair pay, and health care) can reduce cancer disparities. However, to achieve cancer health equity, multilevel approaches are required to ensure that access to high-quality cancer care and equitable receipt of evidence-based services can reduce cancer disparities. Policy, health system interventions, and innovative delivery and health care coverage approaches by private and public payers, employer-based payers, and labor union organizations can assist in ensuring access to and receipt of high-quality cancer care while addressing the high costs of care delivery. Partnerships among patients, caregivers, employers, health care providers, and health care payers can make impactful changes in the way in which cancer care is delivered and, in turn, can assist in reducing cancer disparities.
Cancer Prevention in Low-Resource Countries: An Overview of the Opportunity
Authors: Kamaraju Sailaja , Drope Jeffrey , Sankaranarayanan Rengaswamy , Shastri Surendra
Published: April 2020

Rising trends in the incidence of cancer in low- and middle-income countries (LMICs) add to the existing challenges with communicable and noncommunicable diseases. While breast and colorectal cancer incidence rates are increasing in LMICs, the incidence of cervical cancer shows a mixed trend, with rising incidence rates in China and sub-Saharan Africa and declining trends in the Indian subcontinent and South America. The increasing frequencies of unhealthy lifestyles, notably less physical activity, obesity, tobacco use, and alcohol consumption are causing a threat to health care in LMICs. Also, poorly developed health systems tend to have inadequate resources to implement early detection and adequate basic treatment. Inequalities in social determinants of health, lack of awareness of cancer and preventive care, lack of efficient referral pathways and patient navigation, and nonexistent or inadequate health care funding can lead to advanced disease presentation at diagnosis. This article provides an overview of opportunities to address cancer control in LMICs, with a focus on tobacco control, vaccination for cervical cancer, novel tools to assist with early detection, and screening for breast and other cancers.
How Do We Align Health Services Research and Quality Improvement?
Authors: Das Devika , Wilfong Lalan , Enright Katherine , Rocque Gabrielle
Published: April 2020

Quality improvement (QI) initiatives and health services research (HSR) are commonly used to target health care quality. These disciplines are increasingly important because of the movement toward value-based health care as alternative payment and care delivery models drive institutions and investigators to focus on reducing unnecessary health care use and improving care coordination. QI efforts frequently target medical error and/or efficiency of care through the Plan-Do-Study-Act methodology. Within the QI framework, strategies for data display (e.g., Pareto charts, run charts, histograms, scatter plots) are leveraged to identify opportunities for intervention and improvement. HSR is a multidisciplinary field of study that seeks to identify the most effective way to organize, deliver, and finance health care to maximize the quality and value of care at both the individual and population levels. HSR uses a diverse set of quantitative and qualitative methodologies, such as case-control studies, cohort studies, randomized control trials, and semistructured interview/focus group evaluations. This manuscript provides examples of methodologic approaches for QI and HSR, discusses potential challenges associated with concurrent quality efforts, and identifies strategies to successfully leverage the strengths of each discipline in care delivery.
Approach to Palliative Care Consultation for Patients With Malignant Bowel Obstruction in Gynecologic Oncology: A Qualitative Analysis of Physician Perspectives
Authors: Hoppenot Claire , Hlubocky Fay J. , Chor Julie , Yamada S. Diane , Lee Nita K.
Published: April 2020

PURPOSE:

Malignant bowel obstruction (MBO) from gynecologic cancer is associated with increased symptoms and short survival. A gynecologic oncologist’s approach to palliative care consultation in the setting of MBO has not been well studied—it could be an opportune time for collaboration with palliative care.

MATERIALS AND METHODS:

This qualitative analysis of interviews with gynecologic oncologists focuses on their perspectives on palliative care consultation at the time of MBO. Interviews were analyzed using a framework analysis, and key themes and quotations were extracted.

RESULTS:

We interviewed 15 gynecologic oncologists from 8 institutions in Chicago. They described a variety of expectations from palliative care consultation. Most frequently, they consulted palliative care for specific questions but managed the remainder of the care. Most participants frequently consulted palliative care, but they also worried about fragmentation of care, the timing of when to introduce a new team during MBO, and the selection of appropriate patients for a limited resource. Many participants preferred earlier palliative care consultation, and many described an emotional toll of caring for patients with MBO. Palliative care consultation was most readily discussed for nonsurgical patients.

CONCLUSION:

Participants’ expectations of palliative care consultations during MBO varied and were not always met. We recommend strengthening communication and protocols for palliative care involvement that meet the needs of specific patient populations and physician teams for surgical and nonsurgical patients. More research is needed to better understand how to integrate palliative care into oncologic and surgical care with gynecologic oncologists.
Pheochromocytoma and Paraganglioma in Children and Adolescents: Experience of the French Society of Pediatric Oncology (SFCE)
Authors: de Tersant Marie , Généré Lucile , Freyçon Claire , Villebasse Sophie , Abbas Rachid , Barlier Anne , Bodet Damien , Corradini Nadège , Defachelles Anne-Sophie , Entz-Werle Natacha , Fouquet Cyrielle , Galmiche Louise , Gandemer Virginie , Lacour Brigitte , Mansuy Ludovic , Orbach Daniel , Pluchart Claire , Réguerre Yves , Rigaud Charlotte , Sarnacki Sabine , Sirvent Nicolas , Stephan Jean-Louis , Thebaud Estelle , Gimenez-Roqueplo Anne-Paule , Brugières Laurence
Published: April 2020

Purpose

The purpose of this work is to assess the clinical outcome of pediatric patients diagnosed with pheochromocytoma and paraganglioma (PPGL) detected in France since 2000.

Methods

A retrospective multicenter study was conducted that included all patients younger than 18 years with PPGL diagnosed in France between 2000 and 2016. Patients were identified from 4 different sources: the National Registry of Childhood Solid Tumors, the French Pediatric Rare Tumors Database, the French registry of succinate dehydrogenase (SDH)-related hereditary paraganglioma, and the nationwide TenGen network.

Results

Among 113 eligible patients, 81 children with available data were enrolled (41 with adrenal and 40 with extra-adrenal PPGL). At diagnosis, 11 had synchronous metastases. After a median follow-up of 53 months, 27 patients experienced a new event (n = 7 second PPGL, n = 1 second paraganglioma [PGL], n = 8 local recurrences, n = 10 metastatic relapses, n = 1 new tumor) and 2 patients died of their disease. The 3- and 10-year event-free survival rates were 80% (71%-90%) and 39% (20%-57%),respectively, whereas the overall survival rate was 97% (93%-100%)at 3 and 10 years. A germline mutation in one PPGL-susceptibility gene was identified in 53 of the 68 (77%) patients who underwent genetic testing (SDHB [n = 25], VHL [n = 21], RET [n = 2], HIF2A [n = 2], SDHC [n = 1], SDHD [n = 1], NF1 [n = 1]). Incomplete resection and synchronous metastases were associated with higher risk of events (P = .011, P = .004), but presence of a germline mutation was not (P = .11).

Conclusions

Most pediatric PPGLs are associated with germline mutations and require specific follow-up because of the high risk of tumor recurrence.
Role of Multimodal Cerebral Oximetry Monitoring in the Anesthetic Management of a Patient With High-Grade Intracranial Arteriovenous Malformation: A Case Report
Authors: Ajayan Neeraja , Hrishi Ajay Prasad , Nagendra Vijetha , Sethuraman Manikandan
Published: April 2020

Near-infrared spectroscopy (NIRS) is a noninvasive monitor of regional brain tissue oxygenation, and jugular venous oximetry (SjvO2) is a monitor of global cerebral oxygenation. We report the role of intraoperative multimodal monitoring of cerebral oxygenation in the anesthetic management of a patient with grade III intracranial arteriovenous malformation (AVM) presenting for surgical excision. Real-time monitoring of cerebral oxygenation is of much relevance in high-grade AVMs where anesthetic management is focused on neuroprotection and prevention of cerebral hypoxia. Besides, it also helps in prediction, early detection, and judicious management of perioperative complications, which are commonly encountered in high-grade AVMs.
A Case Report of Slowly Evolving Epidural Hematoma After Lumbar Drain Removal Following Initiation of Clopidogrel Therapy
Authors: Ranganath Yatish S. , Arora Lovkesh , Sondekoppam Rakesh V.
Published: April 2020

Guidelines on the management of lumbar drain in patients receiving antithrombotic therapy are lacking, with American Society of Regional Anesthesia and Pain Medicine (ASRA) anticoagulation guidelines for regional anesthesia providing the best possible guidance for this scenario. However, the risk–benefits of placing a lumbar drain in the context of vascular surgery differ from placement of neuraxial blockade. One of the changes included in the recently published ASRA guidelines is that clopidogrel can be started on a patient with an indwelling neuraxial catheter. We report a case of slowly evolving epidural hematoma following the initiation of clopidogrel therapy in a patient with an indwelling lumbar drain.
Responsible Sourcing Under Supplier-Auditor Collusion
Authors: Chen Li , Yao Shiqing , Zhu Kaijie
Published: April 2020

Problem definition: Although they enjoy low costs in sourcing from emerging economies, global brands also face serious brand and reputation risks from their suppliers’ noncompliance with environmental and labor standards. Such a supplier problem can be viewed as a process quality problem concerning how products are sourced and produced. Academic/practical relevance: Addressing this problem is a key component of many global companies’ responsible sourcing programs. A common approach is to use an audit as an auxiliary supplier screening mechanism. However, in regions with lax law enforcement, an unethical, noncomplying supplier may attempt to bribe an unethical auditor to pass the audit. Such supplier-auditor collusion compromises the integrity of the audit and weakens its effectiveness. Methodology: In this paper, we develop a game-theoretical model to study the effect of supplier-auditor collusion on the buyer’s auditing and contracting strategy in responsible sourcing, as well as various driving factors that help reduce collusion. Results: We show that the buyer’s equilibrium contracting strategy is a shutout contract that takes three different forms, depending on the collusion risk level. We also define and analyze the screening errors and social efficiency loss caused by supplier-auditor collusion. By comparing the cost versus collusion elimination trade-off between a third-party audit and an in-house audit, we offer explanations for why many global brands fully rely on third-party audits and set higher process quality requirements for suppliers located in high-risk countries. The robustness of our insights is verified by two model extensions: one involving additional supplier audit cost and the other allowing for supplier process quality improvement before audit. Managerial implications: These model insights provide useful theoretical support and baseline guidance for the current supplier audit practices in responsible sourcing. Our extended model analysis further demonstrates the importance for global brands to lobby local governments to increase collusion penalties and to promote the ethical level of the third-party auditors located in high-risk countries.
Utilisation of antenatal care services as determinants of satisfaction and its challenges in Lagos, Nigeria
Authors: Ademuyiwa Iyabo Yewande , Opeke Rosaline Oluremi , Odetola Titilayo Dorothy
Published: April 2020

Despite the growing interest and efforts by government to popularise antenatal care services in Nigeria as recommended by the World Health Organization, high levels of infant and maternal mortality remains a major public health challenge facing the country. Complications of pregnancy and childbirth cause more deaths and disabilities than any other reproductive health problems in African countries, including Nigeria. Antenatal care presents an opportunity for recognition and appropriate intervention for some of the causes of maternal mortality in developing countries. The study investigates the level of utilisation of antenatal care services as determinants of satisfaction and its challenges among pregnant women in Lagos, Nigeria. A multistage sampling technique was used to determine the sample size of 1 500 pregnant women. A validated questionnaire was used for data collection. The Cronbach's alpha reliability coefficients for the tools ranged from 0.94–0.97. Data were analysed using descriptive and inferential (correlation, simple and multiple regression) statistics. The results showed that utilisation of antenatal care services had a significant influence on pregnant women's satisfaction with the services. Long waiting hours in the clinic, income/financial constraints, high cost of services and distance to health centres are the major challenges faced by pregnant women in Lagos.
COVID-19 and dental practice
Authors: Sandle Tim
Published: April 2020

Microbiologist Dr Tim Sandle looks at some practical steps that can be taken to minimise any cross-infection risks
Root Caries Part 2: the Restorative Challenge
Authors: Burrows Stephen
Published: April 2020

With the increasing prevalence of root caries of varying complexity, clinicians will face challenges in deciding how best to manage such lesions. Non-operative caries control should be used whenever possible. In this paper factors that can affect success when restoring root caries are discussed.

CPD/Clinical Relevance: The restorative management of root caries can be challenging. Careful attention to detail when restoring root carious lesions is essential to optimize treatment outcome.
Art and Science of Shade Matching
Authors: Khalid Mariya , Chughtai Mohammad Ali
Published: April 2020

Shade selection is an important step in restorative procedures. The objective of this step is to provide aesthetically pleasing restorations which blend in with the existing dentition of the patient. This article highlights clinical difficulties which may hinder proper shade selection and a number of factors causing these difficulties. For ease of understanding, these factors have been divided into four categories. These are factors related to the dentist, the shade matching environment, the material used for shade selection and the patient. Because shade selection is an important step, it is recommended that this step should be given sufficient time. A checklist and a form for shade selection have also been devised to avoid any oversights during shade selection. This will help improve dentist laboratory communication which can result in an improved and aesthetically pleasing restoration.

CPD/Clinical Relevance: Shade selection is a crucial step in the process of fabricating an aesthetically pleasing restoration.
Winning wars: the triumphs and myths of technology
Authors: Hamourtziadou Lily , Jackson Jonathan
Published: April 2020

This paper examines the use of technology in warfare, from the Great War, with
its use of artillery, to the War on Terror, with its breakthrough in air and
drone power. The use of drones, due to their alleged precision, was meant to be
ethical and legal. Strategic bombardment, it was claimed, could win wars. It
would also cement the American claim of superiority, hegemony, and power in the
war against terrorism. We ask if superior technology can guarantee victory and
what that victory would look like, or whether its use can result in such human
loss that a military victory becomes unconscionable. After the failure of
technology to protect life in the 20th century, what has been achieved in the
21st century War on Terror? What constitutes a triumph and to what extent is
that triumph a myth?
The triple paradigm crisis: economy, environment, and security
Authors: Rogers Paul
Published: April 2020

Working towards a more stable and peaceful world is limited by problems within key three areas of human concern, the need for an equitable economic system, the urgent need to respond to climate breakdown and an approach to international security that avoids the common military approach of responding to challenges with early use of force. Instead, the current dominant neoliberal economic model has proved incapable of increasing equity and emancipation and is, instead, encouraging socio-economic marginalisation. It also militates against responding effectively to climate breakdown which requires high levels of economic planning and intergovernmental cooperation and it provides a business environment that favours military industrial complexes that thrive on conflict. Responding to these issues requires the vigorous pursuit of alternative paradigms and the impending issue of climate breakdown, in particular, means that such pursuit must be rapid in its effect.