bluuebunny/crossref_metadata_2025 huggingface dataset:
Prescription Opioid Misuse Motives in US Older Adults
Authors: Schepis Ty S , Wastila Linda , Ammerman Beth , McCabe Vita V , McCabe Sean Esteban
Published: October 2019

Objectives

To evaluate age-based differences in prescription opioid misuse (POM) motives and to evaluate substance use and mental and physical health correlates of POM motive categories in older adults.

Design

Data were from the National Survey on Drug Use and Health (NSDUH), a nationally representative US survey.

Setting

The NSDUH is a household survey.

Subjects

A total of 5,826 US residents with past-year POM; 415 were 50 years and older (7.1%).

Methods

Nine POM motives were assessed among those engaged in past-year POM, grouped into three categories: solely physical pain relief, solely non–pain relief, or mixed motives. Prevalence of POM motives were calculated by age group, with logistic models examining age-based differences. Finally, odds of substance use and mental and physical health correlates by motive category were calculated via logistic models in older adults.

Results

POM motivated solely by physical pain relief increased from 35.1% in young adults to 65.4% in older adults; in older adults, 84.7% of POM episodes involved pain relief as a motive. POM for solely non–pain relief or mixed motives was associated with greater odds, vs pain relief only, of past-year benzodiazepine misuse (odds ratio [OR] = 4.43 and 6.15, respectively), any substance use disorder (OR = 5.57 and 5.60, respectively), and suicidal ideation (OR = 4.05 and 3.56, respectively) in older adults.

Conclusions

. POM motives change over the lifespan, with increasing POM for pain relief with aging. Comprehensive nonopioid pain management is needed for those engaged in POM for pain relief, and substance use and mental health treatment are needed for those with non–pain relief motives.
Evolution and rapid spread of a reassortant A(H3N2) virus that predominated the 2017–2018 influenza season
Authors: Potter Barney I , Kondor Rebecca , Hadfield James , Huddleston John , Barnes John , Rowe Thomas , Guo Lizheng , Xu Xiyan , Neher Richard A , Bedford Trevor , Wentworth David E
Published: October 2019

The 2017–2018 North American influenza season caused more hospitalizations and deaths than any year since the 2009 H1N1 pandemic. The majority of recorded influenza infections were caused by A(H3N2) viruses, with most of the virus’s North American diversity falling into the A2 clade. Within A2, we observe a subclade which we call A2/re that rose to comprise almost 70 per cent of A(H3N2) viruses circulating in North America by early 2018. Unlike most fast-growing clades, however, A2/re contains no amino acid substitutions in the hemagglutinin (HA) segment. Moreover, hemagglutination inhibition assays did not suggest substantial antigenic differences between A2/re viruses and viruses sampled during the 2016–2017 season. Rather, we observe that the A2/re clade was the result of a reassortment event that occurred in late 2016 or early 2017 and involved the combination of the HA and PB1 segments of an A2 virus with neuraminidase (NA) and other segments a virus from the clade A1b. The success of this clade shows the need for antigenic analysis that targets NA in addition to HA. Our results illustrate the potential for non-HA drivers of viral success and necessitate the need for more thorough tracking of full viral genomes to better understand the dynamics of influenza epidemics.
The life aquatic with spiders (Araneae): repeated evolution of aquatic habitat association in Dictynidae and allied taxa
Authors: Crews Sarah C , Garcia Erika L , Spagna Joseph C , Van Dam Matthew H , Esposito Lauren A
Published: October 2019

Despite the dominance of terrestriality in spiders, species across a diverse array of families are associated with aquatic habitats. Many species in the spider family Dictynidae are associated with water, either living near it or, in the case of Argyroneta aquatica, in it. Previous studies have indicated that this association arose once within the family. Here we test the hypothesis of a single origin via the broadest phylogeny of dictynids and related ‘marronoids’ to date, using several taxa that were not previously sampled in molecular analyses to provide the first quantitative test of the hypothesis put forth by Wheeler et al. (2016). We sampled 281 terminal taxa from 14 families, assembling a matrix with 4380 total base pairs of data from most taxa. We also assembled an atlas of morphological traits with potential significance for both ecology and taxonomy. Our resulting trees indicate that an aquatic habitat association has arisen multiple times within dictynids. Dictynidae and the genus Dictyna are polyphyletic and the genera Lathys and Cicurina remain unplaced. A review of aquatic habitat associations in spiders indicates that it occurs in members of at least 21 families. With our morphological atlas, we explore characters that have been implicated in aiding an aquatic lifestyle, which in the past may have caused confusion regarding taxon placement. Our results indicate that not all spiders with traits thought to be useful for aquatic habitat associations occupy such habitats, and that some spider taxa lacking these traits are nonetheless associated with water.
An Executive Summary of Reports From an International Multidisciplinary Roundtable on Exercise and Cancer: Evidence, Guidelines, and Implementation
Authors: Campbell Kristin L. , Winters-Stone Kerri M. , Patel Alpa V. , Gerber Lynn H. , Matthews Charles E. , May Anne M. , Stuiver Martijn M. , Stout Nicole L. , Schmitz Kathryn H. , Morris G. Stephen
Published: October 2019

Physical activity can play an important role in cancer prevention and control, but there is a need to update the state of the science to best facilitate dissemination and implementation of evidence into practice. The American College of Sports Medicine convened an International Multidisciplinary Roundtable on Exercise and Cancer to update recommendations based on current evidence on the role of physical activity and exercise in cancer prevention and survivorship. There was strong evidence for a protective effect of physical activity against colon, breast, endometrial, kidney, bladder, esophagus, and stomach cancer; moderate evidence that pre-diagnosis physical activity may reduce risk of dying from breast and colon cancer; and, moderate evidence that higher levels of physical activity post-diagnosis are associated with lower risk of dying from colon, breast, and prostate cancer. For cancer survivors, an exercise prescription for moderate intensity aerobic and/or resistance exercise at least 3 times per week, 30 minutes/sessions, for at least 8-12 weeks may consistently improve common treatment-related symptoms and side effects. To implement this knowledge, an Exercise Is Medicine approach was adapted to the cancer context. Oncology clinicians are asked to: 1) assess current physical activity levels and safety to engage in exercise, 2) advise patients to increase physical activity if not currently reaching recommended levels, and 3) refer individuals to appropriate services. Exercise can play a vital role in prevention and management of cancer. The Roundtable update provides physical therapists with practical, evidence-based information for utilization of exercise as a treatment strategy and models for implementation.
Proanthocyanidins attenuate breast cancer-induced bone metastasis by inhibiting Irf-3/c-jun activation
Authors: Guo Shuangfei , Zhu Wei , Yin Ziqing , Xiao Ding , Zhang Qiang , Liu Tang , Ni Jiangdong , Ouyang Zhengxiao , Xie Hongming
Published: October 2019

We have previously demonstrated the pivotal role of Jnk-mediated Irf-3/c-Jun in regulating nuclear factor kappa-Β ligand (RANKL)-induced osteoclastogenesis. Here, we demonstrated that proanthocyanidins (PACs) target Irf-3 to alleviate breast cancer-induced activation of osteoclasts. We also found that PACs induced apoptosis of osteoclast precursors by upregulating the ratio of bax/bcl-2 and activating caspase-3 activity. Such bone protective effect also could be observed in a bone metastasis model of breast cancer. These findings provided a novel therapeutic intervention targeting abnormal bone metabolism to alleviate bone metastasis of breast cancer.
Maintaining Safety and Planning for the Future
Authors: Allen Candice , Fehr Karla K. , Nyp Sarah S.
Published: October 2019

CASE:

Kevin is a 12-year-old boy with autism spectrum disorder, intellectual disability (nonverbal intelligence quotient (IQ) scores in mid-40s), and attention-deficit/hyperactivity disorder who has been followed by a developmental-behavioral pediatrician (DBP) and a child psychologist for medication and behavioral management since he was 4 years old. Kevin was placed in the care of his great-great-aunt shortly after he turned 2 years of age because of concerns of neglect. She is now his legal guardian.

Kevin is predominately nonverbal but does use a few single words to make requests or label items. He attends a public school and receives full-time special education support. He has a personal care assistant (PCA) who provides in-home support 5 to 6 days/wk for 3 to 4 hours at a time. The PCA is working on toilet training, using a “clock-training” approach, and also takes Kevin outdoors to play or on short outings during her visits. In his free time, Kevin prefers to watch cooking shows on television.

Over the past year, Kevin's behaviors have become more concerning. There have been several episodes of Kevin waking up during the early morning hours and going to the kitchen to “cook.” After one of these episodes, his guardian was not aware that Kevin had woken up until the next morning when she found a concoction of corn starch, coffee grounds, cottage cheese, and powdered drink mix in the blender. Kevin had also woken up during the night and ventured out of the house into the back yard. His guardian had woken up immediately as the alarm system sounded when he opened the outer door from the house to the yard.

A door alarm was added to Kevin's bedroom door so that his guardian would be alerted when he leaves his bedroom; however, the alarm is not used consistently because there are times when the alarm cannot be found at bedtime. Kevin's guardian was able to obtain a Global Positioning System (GPS) device for him to wear on his shoe from the local police department. He wears this without resistance every day.

Kevin's guardian is in her mid-70s, and she has had several health issues over the past 2 to 3 years. There are no other family members who are willing or able to care for Kevin if his guardian were no longer able to. The DBP and child psychologist have encouraged Kevin's guardian to explore long-term residential care options with the state agency that provides support for individuals with intellectual disabilities and with Kevin's insurance provider, but the guardian is very reluctant to do this. She fears that Kevin will be removed from her care or placed in a “home” where someone will “do bad things to him.”

What else would you recommend or actions would you take to support Kevin's guardian in ensuring Kevin's safety and planning for his future care?
Is Doxycycline Appropriate for Routine Treatment of Young Children With Erythema Migrans?
Authors: Wormser Gary P. , Strle Franc , Shapiro Eugene D.
Published: October 2019

The frequency of permanent staining of teeth of young children from doxycycline is thought to be lower than from older tetracyclines, but the precise risk is uncertain. Until more definitive data become available, doxycycline should not be used routinely to treat young children with erythema migrans, a manifestation of Lyme disease for which other antimicrobials are highly effective.
Development of a Joint Commission Disease-Specific Care Certification Program for Parkinson Disease in an Acute Care Hospital
Authors: Azmi Hooman , Cocoziello Lisa , Harvey Renee , McGee Margaret , Desai Nilesh , Thomas Jewell , Jacob Blessy , Rocco Anthony , Keating Karen , Thomas Florian P.
Published: October 2019

BACKGROUND

Patients with Parkinson disease (PD) admitted to the hospital for any reason are at a higher risk of hospital-related complications. Frequent causes include delays in administering PD medications or use of contraindicated medications. The Joint Commission Disease-Specific Care (DSC) program has been used to establish a systematic approach to the care of specific inpatient populations. Once obtained, this certification demonstrates a commitment to patient care and safety, which is transparent to the public and can improve quality of care.

METHODS

We formalized our efforts to improve the care of hospitalized patients with PD by pursuing Joint Commission DSC. An interprofessional team was assembled to include nurses, therapists, physicians, pharmacists, performance improvement specialists, and data analysts. The team identified quality metrics based on clinical guidelines. In addition, a large educational campaign was undertaken. Application to the Joint Commission for DSC resulted in a successful June 15, 2018 site visit. To our knowledge, this is the first DSC program in PD in an acute care hospital.

CONCLUSION

Using the established platform of DSC certification from the Joint Commission, we developed a program based on relevant metrics that aims to address medication management of patients with PD admitted to the hospital. Our hope is to improve the care of this vulnerable patient population.
Development and Validation of the Self-care in Motor Neuron Disease Index
Authors: Bassola Barbara , Lizio Andrea , Lucchini Marco , Sansone Valeria Ada , Lusignani Maura
Published: October 2019

OBJECTIVE

The aim of this study was to develop and psychometrically test the properties of the Self-care in Motor Neuron Disease (SCMND) Index.

METHODS

This instrument development and validation study was conducted in 3 phases. The first is to identify self-care behaviors in people with motor neuron disease (MND), and the second is to evaluate the content validity of the SCMND Index. Then, between March 2017 and March 2018, the tool was administered to 107 people with MND for psychometric tests.

RESULTS

The SCMND Index was developed based on the middle-range theory of self-care of chronic illness, including 15 self-care behaviors related to respiration, nutrition, mobility, medication, medical visits, and complication management. Content validity was excellent. Data analysis suggests that the instrument has a good internal consistency in all 3 domains and excellent reproducibility. Increased self-care behaviors' median values were associated with mechanical ventilation, cough assistance, and dysphagia. Domains differed significantly based on access (maintenance), hospital admissions (monitoring and management), and respiratory infection (management).

CONCLUSIONS

Self-care is a patient-centered outcome, and it is a key point of healthcare. Results suggest that the SCMND Index is useful for both clinicians and researchers to evaluate self-care in MND.
Night Shift Working Is Associated With an Increased Risk of Thyroid Nodules
Authors: Rizza Stefano , Neri Anna , Capanna Alessandra , Grecuccio Chiara , Pietroiusti Antonio , Magrini Andrea , Federici Massimo , Coppeta Luca
Published: October 2019

Objectives:

To study thyroid alterations in health care workers according to their working status.

Methods:

We performed a retrospective study including 299 hospital employers who underwent in 2016 a periodic health surveillance checks in the Service of Occupational Medicine. According to the working status (rotating night-shift working [no. 160] vs day-working [no. 139]), we divided participant's clinical, anthropometric, and thyroid echographic characteristics.

Results:

Respect to day workers, rotating night-shift workers were slightly older and more frequently male whereas had similar thyroid stimulating hormone, Ft3, Ft4 levels, and autoimmunity (anti-TPO levels more than 30). Univariate and multivariate regression analysis revealed that rotating night shift work is associated to a significantly increased number of thyroid nodules.

Conclusions:

This retrospective report suggests that the alteration in the molecular clocks typical of rotating night-shift workers harbors a higher risk of thyroid nodule development compared with diurnal workers. This novel result deserves replication in larger cohorts since thyroid nodules not rarely can represent thyroid cancers.
Tongue base varix as a source of oral bleeding
Authors: Kim Young-Mo , Kim Ji Won , Park In Suh , Choi Jeong-Seok
Published: October 2019

Rationale:

Oral bleeding is usually diagnosed after by referral to other department for the differential diagnosis of hematemesis or hemoptysis. If a patient presents with blood in the oral cavity with no obvious source, generally upper airway, pulmonary, or gastroesophageal lesions are considered likely bleeding foci. The tongue base is an unusual site for laryngopharyngeal varices and only a few cases have been reported.

Patient concerns:

Although varix at the tongue base in patients with liver cirrhosis has been rarely described, physicians must consider variceal bleeding from the tongue base when presented with oral bleeding. In such cases, bleeding foci can be identified and controlled by laryngoscopy. We describe the case of a 42-year-old woman complaining of small amount of hemoptysis with variceal bleeding at the tongue base controlled by laryngoscopic excision and cauterization.

Diagnosis:

A diagnosis of tongue base varix was made based on medical history, clinical manifestations, laryngoscopic findings and pathologic features for the patient.

Interventions:

The successful laryngoscopic procedures were performed.

Outcomes:

The patient has shown no recurrent oral bleeding during follow-up.

Lessons:

Variceal bleeding in the tongue base is likely to cause serious massive hemorrhage. We need to consider this possibility when presented with a patient with intraoral bleeding but no evidence of hemoptysis or hematemesis.
The association between weight fluctuation and all-cause mortality
Authors: Zhang Yan , Hou Fangfang , Li Jiexue , Yu Haiying , Li Lu , Hu Shilian , Shen Guodong , Yatsuya Hiroshi
Published: October 2019

Background:

Many observational studies have reported an association between weight fluctuation and all-cause mortality. However, the conclusions obtained from these studies have been unclear.

Objective:

The current meta-analysis aimed to clarify the association between weight fluctuation and all-cause mortality.

Data source:

We electronically searched PubMed, Embase, and Web of Science for articles reporting an association between weight fluctuation and all-cause mortality that were published before April 30, 2018.

Study appraisal and synthesis methods:

The methodological quality of each study was appraised using the modified Newcastle Ottawa Quality Assessment Scale. The hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were extracted from the included studies and pooled using random-effect models. Meta-regression approaches were also performed to explore sources of between-study heterogeneity.

Results:

A total of 15 studies were eligible for the current meta-analysis. The pooled overall HR for all-cause mortality in the group with the greatest weight fluctuations compared with the most stable weight category was 1.45 (95% CI: 1.29–1.63). Considerable between-study heterogeneity was observed, some of which was partially explained by the different follow-up durations used by the included studies. Moreover, publication bias that inflated the risk of all-cause mortality was detected using Egger's test (P = .001).

Conclusion:

Weight fluctuation might be associated with an increased risk of all-cause mortality.
The effects of acupuncture on cognitive deficits in transgenic mouse studies of mild cognitive impairment and Alzheimer's disease
Authors: Yang Yang , Hu Shaowen , He Jiang , Zhang Jianguo , Tang Chunzhi
Published: October 2019

Background:

Mild cognitive impairment (MCI) and Alzheimer's disease (AD) are neurodegenerative diseases associated with aging. The major clinical features of both are progressive memory loss and progressive cognitive loss. The objective of this systematic review protocol is to provide the methods for evaluating the effectiveness of acupuncture in the treatment on cognitive deficits in transgenic mouse.

Methods and analysis:

We will search the electronic databases of PubMed, Web of Science, Embase, PsycINFO, as well as the Chinese databases such as Chinese Biomedicine Literature (CBM), Chinese Medical Current Content (CMCC), Chinese Scientific Journal Database (VIP), WanFang Database and China National Knowledge Infrastructure (CNKI) from their inceptions to July 2019. RevMan 5.3 software will be used for the data synthesis and the quality of each study was assessed independently by use of the CAMARADES checklist.

Results:

This review will provide a high-quality synthesis based on present evidence of acupuncture treatment for AD and MCI in transgenic mouse models.

Conclusions:

This systematic review will provide evidence for weather acupuncture is an effective intervention for AD and MCI in transgenic mouse models.

Ethics and dissemination:

Ethical approval is not necessary since this protocol is only for systematic review and does not involve privacy data or conduct an animal experiment. This protocol will be disseminated by a peer-review journal or conference presentation.

Trial registration number:

PROSPERO CRD42019142985.

Strengths and limitations of this study:

This systematic review will be the first to provide new knowledge underlying the effectiveness to improve cognitive function of acupuncture treatment for AD and MCI in transgenic mouse models. The result of this systematic review may provide experimental and theoretical basis for the future clinical application of acupuncture in the treatment of AD.

The limitation of this systematic review may come from language barriers, because only English and Chinese can be included. Also, this study includes various kinds of acupuncture treatments which may result in essential heterogeneity.
Renal dysfunction in patients with radioactive iodine-refractory thyroid cancer treated with tyrosine kinase inhibitors
Authors: Iwasaki Hiroyuki , Yamazaki Haruhiko , Takasaki Hirotaka , Suganuma Nobuyasu , Sakai Rika , Nakayama Hirotaka , Toda Soji , Masudo Katsuhiko
Published: October 2019

In 2014/2015, tyrosine kinase inhibitors (TKIs) were introduced as a secondary treatment for refractory differentiated thyroid cancer (DTC) in Japan. While renal dysfunction is an adverse event of TKI, data on this adverse event in TKI-treated DTC remains insufficient. Here, we investigated renal function in patients undergoing TKI treatment for DTC and evaluated the efficacy of dose reduction/withdrawal for cases of renal dysfunction.

A total of 73 cases of radioactive iodine-refractory DTC treated with sorafenib (n = 22) or lenvatinib (n = 51) were included. Patient data evaluated were TKI treatment period, estimated glomerular filtration rate (eGFR) before and after TKI therapy, incidence and degree (maximum value at time of TKI treatment) of proteinuria, and albumin levels before and after TKI therapy were compared.

The mean ΔeGFR was −6.75% with lenvatinib and +5.90% with sorafenib. It was not significant (P = .15). The mean Δalbumin was −8.90% and −5.85% with lenvatinib and sorafenib, respectively; there was no significant difference between the lenvatinib and sorafenib groups (P = .77). According to our program of TKI dose reduction and withdrawal, all patients except 2 with diabetes were successfully continuing treatment.

Overall, the present results demonstrated that renal function is negatively affected by long-term TKI treatment for RAI-refractory DTC. However, heightened proteinuria, decreased eGFR and albumin levels, and significant but apparently reversible renal dysfunction were more frequent with lenvatinib than sorafenib.
“A patient like me” – An algorithm-based program to inform patients on the likely conditions people with symptoms like theirs have
Authors: Koren Gideon , Souroujon Daniel , Shaul Ran , Bloch Allon , Leventhal Ariel , Lockett Jason , Shalev Varda
Published: October 2019

To date, consumer health tools available over the web suffer from serious limitations that lead to low quality health- related information. While health data in our world are abundant, access to it is limited because of liability and privacy constraints.

The objective of the present study was to develop and evaluate an algorithm-based tool which aims at providing the public with reliable, data-driven information based and personalized information regarding their symptoms, to help them and their physicians to make better informed decisions, based on statistics describing “people like you”, who have experienced similar symptoms.

We studied anonymized medical records of Maccabi Health Care. The data were analyzed by employing machine learning methodology and Natural Language Processing (NLP) tools. The NLP tools were developed to extract information from unstructured free-text written by Maccabi's physicians.

Using machine learning and NLP on over 670 million notes of patients’ visits with Maccabi physicians accrued since 1993, we developed predictors for medical conditions based on patterns of symptoms and personal characteristics.

The algorithm was launched for Maccabi insured members on January 7, 2018 and for members of Integrity Family Care program in Alabama on May 1, 2018.

The App. invites the user to describe her/ his main symptom or several symptoms, and this prompts a series of questions along the path developed by the algorithm, based on the analysis of 70 million patients’ visits to their physicians.

Users started dialogues with 225 different types of symptoms, answering on average 22 questions before seeing how people similar to them were diagnosed. Users usually described between 3 and 4 symptoms (mean 3.2) in the health dialogue.

In response to the question “conditions verified by your doctor”, 82.4% of responders (895/1085) in Maccabi reported that the diagnoses suggested by K's health dialogues were in agreement with their doctor's final diagnosis. In Integrity Health Services, 85.4% of responders (111/130) were in agreement with the physicians’ diagnosis.

While the program achieves very high approval rates by its users, its primary achievement is the 85% accuracy in identifying the most likely diagnosis, with the gold standard being the final diagnosis made by the personal physician in each individual case. Moreover, the machine learning algorithm continues to update itself with the feedback given by users.
Giant atypical lipomatous tumor/well-differentiated liposarcoma affects lower limb activity
Authors: Zhan Haibo , Cao Suixia , Gao Tian , Zhang Bin , Yu Xiaolong , Wang Lizhen , Zeng Jin , Dai Min
Published: October 2019

Rationale:

Liposarcomas are locally invasive mesenchymal soft tissue tumors; most deep liposarcomas are large. Liposarcomas have heterogeneous histomorphology, molecular and genetic characteristics, and clinical prognosis, making the diagnosis and treatment of giant liposarcomas difficult for bone tumor surgeons.

Patient concerns:

A 70-year-old man presented with a mass in the posterior part of his left lower extremity that was first noticed 3 years prior. The mass was initially fist sized but continued to grow and had been affecting lower limb mobility on presentation.

Diagnoses:

Computed tomography and magnetic resonance imaging revealed a large space-occupying lesion in the left thigh muscles, which was identified as a low-grade malignant tumor. Postoperative pathology results confirmed the diagnosis of atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDLPS).

Interventions:

The patient underwent open surgery to completely remove the tumor tissue and relieve pain.

Outcomes:

At the 10-month follow-up appointment, the patient had recovered well, function of the lower extremities had returned to normal, and no signs of recurrence or metastasis were noted.

Lessons:

Although ALT/WDLPS is a locally invasive tumor with good prognosis, delayed treatment is associated with increased tumor size, which can affect lower limb mobility. Therefore, we believe that extensive surgical resection of tumor tissue is a suitable treatment for all ALT/WDLPS cases in order to avoid possible local recurrence. In addition, for ALT/WDLPS tumors that are difficult to extensively excise, long-term follow-ups are necessary due to the possibility of recurrence.
A nomogram to predict cognitive impairment after supratentorial spontaneous intracranial hematoma in adult patients
Authors: Gong Kai , Zhao Lizheng , Guo Jianfeng , Wang Zhanxiang
Published: October 2019

To establish a nomogram model to predict early cognitive impairment after supratentorial spontaneous intracranial hematoma in adult patients.

A retrospective cohort study was held between January 2016 and October 2018. One hundred twenty seven out of 170 consecutive patients with supratentorial spontaneous intracranial hematoma were enrolled in this study. They were divided into development (n = 92) and validation (n = 35) dataset according to their admission time. Mini-mental State Examination (MMSE) was conducted between the third and the sixth month after the onset of stroke. MMSE ≤ 24 was considered as cognitive impairment. Univariate and multivariate logistic regression was used to screen for independent risk factors which correlate with cognitive impairment on the development dataset. A nomogram was built based on Akaike Information Criterion (AIC). Receiver operating characteristic (ROC) curve and calibration curve on development and validation dataset was drawn with each area under the curves (AUC) calculated. The decision curve analysis was also conducted with the development dataset.

The bleeding volume, Glasgow Coma Scale (GCS), and intraventricular hemorrhage (IVH) are the most significant risk factors which may cause cognitive impairment both in the univariate and multivariate analysis. The finial model performed good discrimination ability on both development and validation dataset with AUC 0.911 and 0.919. Most patients would benefit from the model according to the decision curve analysis.

A nomogram, constructed based on bleeding volume, GCS, and IVH can provide a feasible tool to evaluate cognitive impairment after supratentorial spontaneous intracranial hematoma in adult patients.
Human neural stem cell transplant location–dependent neuroprotection and motor deficit amelioration in rats with penetrating traumatic brain injury
Authors: Hu Zhen , Gajavelli Shyam , Spurlock Markus S. , Mahavadi Anil , Quesada Liz S. , Gajavelli Ganesh R. , Andreoni Cody B. , Di Long , Janecki Julia , Lee Stephanie W. , Rivera Karla N. , Shear Deborah A. , Bullock Ross M.
Published: October 2019

BACKGROUND

Penetrating traumatic brain injury induces chronic inflammation that drives persistent tissue loss long after injury. Absence of endogenous reparative neurogenesis and effective neuroprotective therapies render injury-induced disability an unmet need. Cell replacement via neural stem cell transplantation could potentially rebuild the tissue and alleviate penetrating traumatic brain injury disability. The optimal transplant location remains to be determined.

METHODS

To test if subacute human neural stem cell (hNSC) transplant location influences engraftment, lesion expansion, and motor deficits, rats (n = 10/group) were randomized to the following four groups (uninjured and three injured): group 1 (Gr1), uninjured with cell transplants (sham+hNSCs), 1-week postunilateral penetrating traumatic brain injury, after establishing motor deficit; group 2 (Gr2), treated with vehicle (media, no cells); group 3 (Gr3), hNSCs transplanted into lesion core (intra); and group 4 (Gr4), hNSCs transplanted into tissue surrounding the lesion (peri). All animals were immunosuppressed for 12 weeks and euthanized following motor assessment.

RESULTS

In Gr2, penetrating traumatic brain injury effect manifests as porencephalic cyst, 22.53 ± 2.87 (% of intact hemisphere), with p value of <0.0001 compared with uninjured Gr1. Group 3 lesion volume at 17.44 ± 2.11 did not differ significantly from Gr2 (p = 0.36), while Gr4 value, 9.17 ± 1.53, differed significantly (p = 0.0001). Engraftment and neuronal differentiation were significantly lower in the uninjured Gr1 (p < 0.05), compared with injured groups. However, there were no differences between Gr3 and Gr4. Significant increase in cortical tissue sparing (p = 0.03), including motor cortex (p = 0.005) was observed in Gr4 but not Gr3. Presence of transplant within lesion or in penumbra attenuated motor deficit development (p < 0.05) compared with Gr2.

CONCLUSION

In aggregate, injury milieu supports transplanted cell proliferation and differentiation independent of location. Unexpectedly, cortical sparing is transplant location dependent. Thus, apart from cell replacement and transplant mediated deficit amelioration, transplant location–dependent neuroprotection may be key to delaying onset or preventing development of injury-induced disability.

LEVEL OF EVIDENCE

Preclinical study evaluation of therapeutic intervention, level VI.
Unsupervised generative and graph representation learning for modelling cell differentiation
Authors: Bica Ioana , Andrés-Terré Helena , Cvejic Ana , Liò Pietro
Published: October 2019

Using machine learning techniques to build representations from biomedical data can help us understand the latent biological mechanism of action and lead to important discoveries. Recent developments in single-cell RNA-sequencing protocols have allowed measuring gene expression for individual cells in a population, thus opening up the possibility of finding answers to biomedical questions about cell differentiation. In this paper, we explore unsupervised generative neural methods, based on the variational autoencoder, that can model cell differentiation by building meaningful representations from the high dimensional and complex gene expression data. We use disentanglement methods based on information theory to improve the data representation and achieve better separation of the biological factors of variation in the gene expression data. In addition, we use a graph autoencoder consisting of graph convolutional layers to predict relationships between single-cells. Based on these models, we develop a computational framework that consists of methods for identifying the cell types in the dataset, finding driver genes for the differentiation process and obtaining a better understanding of relationships between cells. We illustrate our methods on datasets from multiple species and also from different sequencing technologies.
Caffeine-induced Plasticity of Grey Matter Volume in Healthy Brains: A placebo-controlled multimodal within-subject study
Authors: Lin Y.-S. , Weibel J. , Landolt H.-P. , Santini F. , Meyer M. , Borgwardt S. , Cajochen C. , Reichert C.
Published: October 2019

Disturbed sleep homeostatic states have been found to alter neuronal homeostasis and reduce grey matter (GM) volume. Caffeine intake that interferes with sleep homeostasis through antagonizing adenosine receptors can impair hippocampal synaptic strength, neurogenesis, as well as memory and learning in rats. In this study, reduced medial temporal GM volume was observed after daily caffeine intake in humans (3 × 150 mg × 10 days compared to 10-day placebo administration). The potential bias from reduced cerebral blood flow was controlled, and the GM reduction was independent of the change in sleep pressure. A decrease in working memory during daily caffeine intake was observed, albeit no association with the magnitude of GM changes. The findings indicate that daily caffeine intake might induce rapid cerebral plasticity and be detrimental for higher order cognitive performance in the long run. They may call into question whether the neuroprotective effects of caffeine found in acute or low dose administration in animals are generalizable onto the daily usage in humans.
The Role of State Uncertainty in the Dynamics of Dopamine
Authors: Mikhael John G. , Kim HyungGoo R. , Uchida Naoshige , Gershman Samuel J.
Published: October 2019

Reinforcement learning models of the basal ganglia map the phasic dopamine signal to reward prediction errors (RPEs). Conventional models assert that, when a stimulus predicts a reward with fixed delay, dopamine activity during the delay should converge to baseline through learning. However, recent studies have found that dopamine ramps up before reward in certain conditions even after learning, thus challenging the conventional models. In this work, we show that sensory feedback causes an unbiased learner to produce RPE ramps. Our model predicts that, when feedback gradually decreases during a trial, dopamine activity should resemble a ‘bump,’ whose ramp-up phase should furthermore be greater than that of conditions where the feedback stays high. We trained mice on a virtual navigation task with varying brightness, and both predictions were empirically observed. In sum, our theoretical and experimental results reconcile the seemingly conflicting data on dopamine behaviors under the RPE hypothesis.
Activin receptor ALK4 coordinates extracellular signals and intrinsic transcriptional programs to regulate development of cortical somatostatin interneurons
Authors: Göngrich Christina , Krapacher Favio A. , Munguba Hermany , Fernández-Suárez Diana , Andersson Annika , Hjerling-Leffler Jens , Ibáñez Carlos F.
Published: October 2019

Although the role of transcription factors in fate specification of cortical interneurons is well established, how these interact with extracellular signals to regulate interneuron development is poorly understood. Here we show that the activin receptor ALK4 is a key regulator of the specification of somatostatin interneurons. Mice lacking ALK4 in GABAergic neurons of the medial ganglionic eminence (MGE) showed marked deficits in distinct subpopulations of somatostatin interneurons from early postnatal stages of cortical development. Specific loses were observed among distinct subtypes of somatostatin+/Reelin+double-positive cells, including Hpse+layer IV cells targeting parvalbumin+interneurons, leading to quantitative alterations in the inhibitory circuitry of this layer. Activin-mediated ALK4 signaling in MGE cells induced interaction of Smad2 with SATB1, a transcription factor critical for somatostatin interneuron development, and promoted SATB1 nuclear translocation and repositioning within the somatostatin gene promoter. These results indicate that intrinsic transcriptional programs interact with extracellular signals present in the environment of MGE cells to regulate cortical interneuron specification.
Normative Data for an Expanded Set of Stimuli for Testing High-Level Influences on Object Perception: OMEFA-II
Authors: Flowers Colin S. , Orsten-Hooge Kimberley D. , Jannuzi Barnes G.L. , Peterson Mary A.
Published: October 2019

We present normative data for bipartite displays used to investigate high-level contributions to object perception in general and to figure-ground perception in particular. In these vertically-elongated displays, two equal-area regions of different luminance abut a central, articulated, vertical border. In Intact displays, a portion of a mono-oriented well-known (“familiar”) object is sketched along one side of the border; henceforth the “critical side.” The other side is the “complementary side.” We measured inter-subject agreement among 32 participants regarding objects depicted on the critical and complementary sides of the borders of Intact displays and two other types of displays: upright and inverted Part-Rearranged displays. The parts on the critical side of the border are the same in upright Intact and Part-Rearranged displays but spatially rearranged into a new configuration in the latter. Inter-subject agreement is taken to index the extent to which a side activates traces of previously seen objects near the central border. We report normative data for 288 regions near the central borders of 144 displays (48/type) and a thorough description of the image features. This set of stimuli is larger than an older “Object Memory Effects on Figure Assignment” (OMEFA) set. This new OMEFA-II set of high-resolution displays is available online (https://osf.io/j9kz2/).
Complex Autoinflammatory Syndrome Unveils Fundamental Principles of JAK1 Transcriptional and Biochemical Function
Authors: Gruber Conor , Calis Jorg , Buta Sofija , Evrony Gilad , Martin Jerome , Uhl Skyler , Caron Rachel , Jarchin Lauren , Dunkin David , Phelps Robert , Webb Bryn , Saland Jeffrey , Merad Miriam , Orange Jordan , Mace Emily , Rosenberg Brad , Gelb Bruce , Bogunovic Dusan
Published: October 2019

Autoinflammatory disease can result from monogenic errors of immunity. We describe herein the first example of a patient with early-onset widespread autoinflammation resulting from a mosaic, heterozygous, gain-of-function mutation (S703I) in JAK1, encoding a kinase essential for signaling downstream of over twenty-five cytokines. By first-of-its-kind custom single-cell RNA sequencing, we examine mosaicism with single cell resolution. We uncover that JAK1 transcription is predominantly restricted to a single allele across different immune cells, introducing the concept of a mutational “transcriptotype” that differs from the genotype. Functionally, the S703I mutation not only increased JAK1 kinase activity, but also resulted in transactivation of partnering JAKs, independently of its catalytic domain. Further, S703I JAK1 was not solely hypermorphic for cytokine signaling, but neomorphic as well, as it enabled downstream signaling cascades not canonically mediated by JAK1. Given these results, the patient was treated with tofacitinib, a JAK inhibitor, which led to rapid resolution of her clinical disease. Together, these findings represent an unprecedented degree of personalized medicine with the concurrent discovery of fundamental biological principles.
Analytical investigation of non-Fickian receptor-mediated endocytosis
Authors: Rismanian Milad , Damirchi Behzad
Published: October 2019

The most important process in which viruses and bioparticles can enter the animal cell is receptor mediated endocytosis. The main propellant of this phenomenon is the attraction between receptor molecules floating in the lipid bilayer membrane of the host cell and ligand molecules on the target. In this paper, the aforementioned phenomenon is investigated analytically assuming that the diffusion model of the receptor molecules in the lipid bilayer is non-Fickian. Penetration time of the target molecule in the host cell shows that there is a critical limit for the target molecule size. The molecules larger than this critical size will experience an oscillatory motion without passing the host cell membrane. For instance, it is found that the maximum diameter for a typical target molecule with dimensionless relaxation time of 5 for receptor diffusion into a cell membrane is 0.22 of the membrane length.
Measuring and enhancing organisational creative climate, knowledge sharing, and innovative work behavior in startups development
Authors: Munir Rosintansafinas , Beh Loo-See
Published: October 2019

Purpose

The purpose of this paper is to examine the role of the organizational creative climate, knowledge sharing and innovative work behavior in startups development. This study also aims to discover the R square, predictive relevance and effect size of the developed model.

Design/methodology/approach

A quantitative method was used, and a total of 352 usable questionnaires were collected from employees at startups particularly in services sector in Malaysia. The structural equation was developed to explain the complicated relationship between organizational creative climate, knowledge sharing and innovative work behavior. The results of hypothesis were analyzed using structural equation modeling – partial least square (SEM-PLS) test.

Findings

The results indicate that organizational creative climate significantly influence innovative work behavior (H1), organizational climate positively affects knowledge sharing (H2) and knowledge sharing significantly influence innovative work behavior (H3). In addition, the results also show that the R square values of innovative work behavior is weak (R2= 0.067), while the predictive relevance value demonstrating the model has sufficient predictive relevance. Further, the results of effect size show medium effect for organizational creative climate and knowledge, while the remaining indicates small effect size.

Practical implications

This study provides a comprehensible and clear understanding on how organizational creative climate and knowledge sharing play important role in fostering the individual innovative work behavior in Malaysian startups.

Originality/value

Research on the significance of organizational creative climate, knowledge sharing and to innovative work behavior particularly in the startups context has not been sufficiently explored. This study shed new light to the startups eco-system stakeholders in stimulating individual innovative work behavior through the practices of sharing information as well as the creative climate and innovative elements in the entrepreneurial activities.
Deploying artificial neural networks for modeling energy demand: international evidence
Authors: Bannor B. Emmanuel , Acheampong Alex O.
Published: October 2019

Purpose

This paper aims to use artificial neural networks to develop models for forecasting energy demand for Australia, China, France, India and the USA.

Design/methodology/approach

The study used quarterly data that span over the period of 1980Q1-2015Q4 to develop and validate the models. Eight input parameters were used for modeling the demand for energy. Hyperparameter optimization was performed to determine the ideal parameters for configuring each country’s model. To ensure stable forecasts, a repeated evaluation approach was used. After several iterations, the optimal models for each country were selected based on predefined criteria. A multi-layer perceptron with a back-propagation algorithm was used for building each model.

Findings

The results suggest that the validated models have developed high generalizing capabilities with insignificant forecasting deviations. The model for Australia, China, France, India and the USA attained high coefficients of determination of 0.981, 0.9837, 0.9425, 0.9137 and 0.9756, respectively. The results from the partial rank correlation coefficient further reveal that economic growth has the highest sensitivity weight on energy demand in Australia, France and the USA while industrialization has the highest sensitivity weight on energy demand in China. Trade openness has the highest sensitivity weight on energy demand in India.

Originality/value

This study incorporates other variables such as financial development, foreign direct investment, trade openness, industrialization and urbanization, which are found to have an important effect on energy demand in the model to prevent underestimation of the actual energy demand. Sensitivity analysis is conducted to determine the most influential variables. The study further deploys the models for hands-on predictions of energy demand.