bluuebunny/crossref_metadata_2025 huggingface dataset:
Initial Choice of Spinal Manipulation Reduces Escalation of Care for Chronic Low Back Pain Among Older Medicare Beneficiaries
Authors: Whedon James M. , Kizhakkeveettil Anupama , Toler Andrew WJ. , Bezdjian Serena , Rossi Daniel , Uptmor Sarah , MacKenzie Todd A. , Lurie Jon D. , Hurwitz Eric L. , Coulter Ian , Haldeman Scott
Published: September 2021

Study Design.

We combined elements of cohort and crossover-cohort design.

Objective.

The objective of this study was to compare longterm outcomes for spinal manipulative therapy (SMT) and opioid analgesic therapy (OAT) regarding escalation of care for patients with chronic low back pain (cLBP).

Summary of Background Data.

Current evidence-based guidelines for clinical management of cLBP include both OAT and SMT. For long-term care of older adults, the efficiency and value of continuing either OAT or SMT are uncertain.

Methods.

We examined Medicare claims data spanning a five-year period. We included older Medicare beneficiaries with an episode of cLBP beginning in 2013. All patients were continuously enrolled under Medicare Parts A, B, and D. We analyzed the cumulative frequency of encounters indicative of an escalation of care for cLBP, including hospitalizations, emergency department visits, advanced diagnostic imaging, specialist visits, lumbosacral surgery, interventional pain medicine techniques, and encounters for potential complications of cLBP.

Results.

SMT was associated with lower rates of escalation of care as compared to OAT. The adjusted rate of escalated care encounters was approximately 2.5 times higher for initial choice of OAT vs. initial choice of SMT (with weighted propensity scoring: rate ratio 2.67, 95% confidence interval 2.64–2.69, P < .0001).

Conclusion.

Among older Medicare beneficiaries who initiated long-term care for cLBP with opioid analgesic therapy, the adjusted rate of escalated care encounters was significantly higher as compared to those who initiated care with spinal manipulative therapy.

Level of Evidence: 3
Audit and Comparison Between Radiographic Markers of Gaze Direction Using EOS Imaging – An Essential Step to Streamline Existing Methods
Authors: Hey Hwee Weng Dennis , Lim Joel Xue Yi , Tan Chuen Seng , Liu Gabriel Ka Po , Wong Hee Kit
Published: September 2021

Study Design.

Retrospective cohort study on prospectively implemented EOS protocol.

Objective.

This study aims to audit and compare existing radiological definitions of gaze direction—chin brow vertical angle (CBVA), McGregor slope (McGS), slope of line of sight (SLS), orbital-internal occipital protuberance (OIOP) slope angle, and Tangent to the hard palate (THP) in a neutral, healthy, and asymptomatic cohort.

Summary of Background Data.

The ability to accurately define direction of gaze is the first step when striving for horizontal gaze restoration in any affected individual with rigid sagittal deformity. Yet, the radiological definition of gaze direction remains poorly standardized.

Methods.

Hundred healthy subjects who could achieve horizontal gaze underwent whole-body standing EOS radiographs taken under a strictly standardized protocol. Radiographic measurements of global spinal sagittal parameters and surrogate measures of horizontal gaze were analyzed and compared.

Results.

The mean age was 45 ± 15.9 years, with a balanced male-to-female-ratio. Their C7 SVA was −7.7 mm ± 24.8 mm, PI was 51.0o ± 11.4o, PI-LL was −0.9o ± 13.0o and T1-slope was 21.2o ± 9.2o. Measured horizontal gaze parameters were as follows: CBVA (1.07o ± 5.48o), McGS (−3.23o ± 5.63o), SLS (0.45o ± 5.34o), OIOP (5.03o ± 4.66o), THP (-0.17o ± 6.27o). CBVA correlated strongly with McGS (r = 0.679, P < 0.001), SLS (r = 0.592, P < 0.001), OIOP (r = 0.697, P < 0.001), and THP (r = −0.504, P < 0.001). OIOP had the lowest variance amongst all parameters and showed less variability compared to CBVA (SD 4.66 Var 21.69 vs. SD 5.48 Var 30.08, P = .012). Multivariate analysis showed that C2-7 angle was the only parameter found to be associated with OIOP values (P = 0.006).

Conclusion.

OIOP is the least variable, and most robust radiological method in determining gaze direction. It uses easily recognizable anatomical landmarks and an angular criterion, which makes it advantageous both with x-rays or slot scanners.

Level of Evidence: 3
Emotional Intelligence and Role-Modeling Nursing's Soft Skills
Authors: Kaiafas Kristen N.
Published: September 2021

Developing and enhancing emotional intelligence in nursing students is a necessary element of nursing education. Various evidence-based strategies to cultivate emotional intelligence characteristics, such as self-reflection, self-awareness, problem-solving, and interprofessional collaboration in nursing students, are described along with the value of role-modeling Christian qualities that promote empathy and compassion in nursing graduates.
Faith Community Nursing
Authors: Long Elizabeth M.
Published: September 2021

The number of older adults worldwide is growing; the incidence of social isolation and loneliness among this population is also increasing. Social isolation and loneliness can have significant physical, mental, and spiritual impacts. Faith community nurses are in an optimal position to identify and intervene to help faith communities reduce the social isolation and loneliness among community-dwelling older adults. Risk factors and tools to identify both circumstances are discussed along with interventions and a case study.
A Christian Response to Lateral Violence Against Nurses
Authors: Ott Cindy
Published: September 2021

Lateral or horizontal workplace violence is experienced by many nurses, particularly new nurses. Personal experiences of being bullied as a new nurse are shared. A Christian perspective for dealing with lateral violence is presented.
Arterial stiffness and age moderate the association between physical activity and global cognition in older adults
Authors: Noriega de la Colina Adrián , Badji Atef , Lamarre-Cliche Maxime , Bherer Louis , Girouard Hélène , Kaushal Navin
Published: September 2021

Background:

Evidence supports that time spent on physical activity has beneficial effects on cognition in older adults. Nevertheless, whether these beneficial effects are still present at the intersection of different levels of arterial stiffness and age is uncertain.

Methods:

One hundred and ten healthy older adults aged 60–75 years were examined for arterial stiffness [carotid–femoral pulse wave velocity (cf-PWV)], global cognition (composite score of Montreal Cognitive Assessment, and Mini-Mental State Examination), and self-reported physical activity (PACED diary). Using PROCESS macro for SPSS, we evaluated if cf-PWV (moderator 1), and age (moderator 2) moderate the relationship between physical activity (X) and global cognition (Y). The threshold for high stiffness was set at 8.5 m/s based on previous studies that reported this cut-off as more appropriate for classifying cerebrovascular risk groups.

Results:

Physical activity had a positive effect on cognition in young-elderly adults (<68.5 years) with a cf-PWV of at least 8.5 m/s (β = 0.48, SE = 0.193, P = 0.014, 95% CI = 0.100--0.868) and in elderly adults (≥68.5 years) with a cf-PWV of less than 8.5 m/s (β = 0.56, SE = 0.230, P = 0.017, 95% CI = 0.104–1.018). This was not the case in elderly adults with a cf-PWV of at least 8.5 m/s (β = 0.00, SE = 0.193, P = 0.998, 95% CI = −0.362 to 361), or in young-elderly adults with a cf-PWV of less than 8.5 m/s (β = 0.16, SE = 0.247, P = 0.501, 95% CI = −0.326 to 656).

Conclusion:

The interaction between arterial stiffness and age moderated the effect of physical activity on global cognition. Time spent on physical activity alone might not be sufficient to achieve cognitive benefit over a specific threshold of arterial stiffness and age.
Common Differential Diagnostic Issues in Soft Tissue Pathology
Authors: Behtaj Mohadese , Hakim Muhammad Omar , Velez Torres Jaylou , Rosenberg Andrew E. , Montgomery Elizabeth Anne
Published: September 2021

In this review, we discuss 4 differential diagnostic considerations that commonly arise in soft tissue pathology, namely, separating myxoid liposarcoma from myxofibrosarcoma, nodular fasciitis from a host of spindle cell sarcoma types, fibrous histiocytoma from dermatofibrosarcoma protuberans, and atypical lipomatous tumor from several nonneoplastic congeners. These topics were chosen as means to highlight several areas of soft tissue pathology, focusing on some of the most common issues in soft tissue pathology.
Malignant Diffuse Tenosynovial Giant Cell Tumor: Case Report and Review of the Literature
Authors: MacMahon Aoife , Chaudhry Yash , James Aaron W. , McCarthy Edward M. , Llosa Nicolas J. , Ahlawat Shivani , Morris Carol D.
Published: September 2021

Diffuse-type tenosynovial giant cell tumor (TGCT) is a neoplasm that exhibits infiltrative growth, tends to recur locally, and is often located within a joint. We describe a challenging diagnosis and clinical course of a 14-year-old girl with malignant diffuse TGCT, highlighting the difficulty of acquiring a representative biopsy. The patient presented with a painful foot mass, which was diagnosed initially through open biopsy as chronic osteomyelitis. Because her pain persisted, additional open biopsies were performed 1 and 2.5 years after the initial biopsy, which also showed features of benign TGCT. At age 16 years, she underwent marginal resection but developed local recurrence with metastatic disease 1 year later. Core needle biopsy of the foot mass again confirmed diffuse TGCT and showed no evidence of atypical or malignant features. Malignant features were confirmed only through excisional biopsy of chest wall metastasis. The patient started chemotherapy and underwent below-the-knee amputation at age 17 years. Amputation specimen showed malignant diffuse TGCT. She died of disease progression approximately 1 year later. Metastasis of diffuse TGCT with benign histology is challenging to diagnose. Previous studies have also found that benign diffuse TGCT can transform into an aggressive, malignant tumor. This case highlights that biopsy sampling can be challenging in histologically heterogeneous tumors. Initial evaluation by a multidisciplinary team, as well as image-guided biopsy techniques, may increase diagnostic accuracy of the biopsy.
Pandemic Autopsy Biosafety Considerations
Authors: Brooks Erin G.
Published: September 2021

At autopsy, prosectors have always risked exposure to a wide array of infectious agents. With the recent advent of the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic, such exposure concerns have increased dramatically. Careful assessment of facility infrastructure and appropriate biosafety training, however, can minimize risks and allow for safe autopsy performance. As with other disease outbreaks, the living have much to learn from the dead. To date, autopsy studies have been critical in elucidating the mechanisms by which COVID-19 (coronavirus disease 2019) may critically compromise not only pulmonary but also cerebral, cardiac, and renal function. Much remains unknown, though, and further tissue-based research is called for. The following review is intended to detail best practices and principles for autopsy biosafety, with a focus on issues specific to the current pandemic.
SARS-CoV-2–Associated Myocarditis at Autopsy
Authors: Singh Ravi B. , Jung Geunyoung , Brooks Erin G.
Published: September 2021

The COVID-19 pandemic has been a major cause of mortality worldwide. While respiratory pathology seems to be the major mechanism of disease, cardiovascular pathology has increasingly been reported to play a role in adverse outcomes. A variety of different cardiovascular histopathologies have been reported at postmortem examination including myocarditis. Because of limited autopsy numbers and lack of standardized reporting of such cases, however, the prevalence of COVID-19 (2019 coronavirus disease)–associated myocarditis is unknown. The current autopsy case report illustrates how COVID-19 pulmonary pathology can be accompanied by right ventricular myocarditis. The discussion reviews the pathophysiology of myocarditis, as well as diagnostic strategies, adding to the growing body of literature describing myocarditis in association with COVID-19 disease.
Lung Adenocarcinoma Metastatic to the Cervix: Report of a Rare Case and Review of the Literature
Authors: Hosseini Hossein , Steinberg Jordan M. , Ratzon Fanni , Unger Pamela , Yurovitsky Alyssa
Published: September 2021

Metastatic involvement of the cervix by nongynecologic malignancies is an extremely rare occurrence. We report a case of metastatic lung adenocarcinoma to the cervix. The patient is a 70-year-old woman who was admitted because of acute kidney injury. Imaging studies revealed left-sided hydronephrosis and a 3.2-cm heterogeneous pelvic mass involving the left pelvic wall. The patient underwent hysteroscopy with dilatation and curettage. Specimens labeled with endometrial and endocervical curettings were notable for tumor cells infiltrating the fibromuscular tissue. Immunohistochemical studies showed that the tumor cells were positive for CK7, napsin A, and TTF1, whereas they were negative for PAX8, p16, p40, p53, GATA3, and ER. This immunophenotype was consistent with a metastatic adenocarcinoma of the lung primary.
Localized Mesothelioma of the Pleura: Report of 2 Cases, From Benign to Malignant
Authors: Canbeldek Leyla , Legesse Teklu , Burke Allen
Published: September 2021

Localized mesotheliomas of the pleura are rare, and form a spectrum of low-grade noninvasive indolent lesions that are presumably benign, to more aggressive invasive cancers that, although fully malignant, have a relatively better prognosis than the diffuse type of mesothelioma. Localized mesotheliomas can be either epithelioid, sarcomatoid, or biphasic. The defining characteristics are circumscription and origin from the visceral pleura. The vast majority are single lesions, although multifocal ones, as the second case in this report, have rarely been described. We present a “benign” localized epithelioid mesothelioma and a malignant localized sarcomatoid mesothelioma with multiple satellite nodules.
Fraternal Coopers Develop Sinonasal Intestinal-Type Adenocarcinoma
Authors: Mallinger Wesley D. , Read Paul W. , Stelow Edward B.
Published: September 2021

We describe 2 brothers with a history of working in the family business of whiskey barrel making who both developed sinonasal intestinal-type adenocarcinomas (ITACs) around their seventh decade of life. This highlights the strong association of ITAC with occupational wood dust exposure, and the typical development of disease occurring around the sixth to seventh decade of life. Intestinal-type adenocarcinomas show morphologic and phenotypic similarities to their primary intestinal counterparts, particularly expression of CDX2 and CK20. Despite the morphologic and phenotypic similarities, the molecular alterations that are common to many adenocarcinomas of the intestinal tract are not present in ITAC. This description highlights the wide morphologic spectrum of ITAC and the often protracted course of this disease process.
Human Papillomavirus–Related Multiphenotypic Sinonasal Carcinoma
Authors: Crawford Michael P. , Stelow Edward B.
Published: September 2021

Human papillomavirus–related mulitphenotypic sinonasal carcinoma is a recently described high-grade malignancy demonstrating significant morphologic overlap with adenoid cystic carcinoma and other salivary-type malignancies. We present a prototypical case of human papillomavirus–related mulitphenotypic sinonasal carcinoma in a 51-year-old woman and discuss the diagnosis, as well as the differential diagnosis.
The Vision of Blindness—Sight Versus Insight: A Case Report and Literature Review of Self-enucleation (Oedipism)
Authors: Vasilopoulou Polyxeni , Giannakopoulos Orestis , Beis Pavlos , Konstantinou Gerasimos N.
Published: September 2021

Self-enucleation or “Oedipism” is a rare ophthalmic and psychiatric emergency. Given the severity of its consequences, it requires proper medical management and that clinicians understand and be aware of the psychiatric presentation. Important clinical considerations include identification of various etiologies leading to self-enucleation, awareness of possible complications, and provision of appropriate care. We present a case of bilateral self-enucleation by a young male patient in the context of his first episode of psychosis and review the literature on this clinical entity. Ocular damage interferes significantly with activities of daily living and is associated with decreased quality of life so that identifying risk factors is of major importance to prevent this dangerous behavior.
Ultrasonographic Features of Hypertrophic Interureteral Cristae in Transabdominal and Transrectal Ultrasonography
Authors: Wang Xiaofeng , Nie Fang , Li Yan , Li Jing
Published: September 2021

Purpose

The aim of this study was to determine the value of transrectal ultrasound in the definitive diagnosis of hypertrophic interureteral cristae and to provide a definitive diagnostic basis for clinical treatment.

Materials and Methods

When the patient's bladder fills moderately, the ultrasound physician uses the transabdominal ultrasound probe to examine the patient's bladder and prostate carefully, focusing on bilateral ureterovesical portals, a cord-like hyperechoic structure visible between the bilateral ureterovesical portals. For further detailed observation, transrectal probe was used to measure the size of Hypertrophic Interureteral Cristae and describe the shape and internal echo. After the examination, the residual urine volume of bladder was measured after one-time urination.

Results

Hypertrophic interureteral cristae was a trilinear structure with a “high-low-high” echo. All the 33 patients had bladder wall thickening. In 9 cases of overfilling of bladder, there were slightly dilated ureterovesical portals at both ends of hypertrophic interureteral cristae. Thirty cases of benign prostatic hyperplasia, 11 patients who had undergone prostate hyperplasia surgery, 26 cases with different degrees trabecular and reticular hyperplasia of bladder wall, there were 9 cases with bladder diverticulum and 23 cases with mild hydronephrosis.

Conclusions

Transrectal ultrasound can confirm the diagnosis of Hypertrophic Interureteral Cristae.
The Rare, the Odd, and the Atypical
Authors: Houser Margaret , Khati Nadia J.
Published: September 2021

Understanding a variety of scrotal diseases is essential to developing an accurate differential diagnosis and is critical in providing optimal patient care. Ultrasound is the imaging modality of choice when evaluating for scrotal pathology, with the major purpose of locating such pathology to either the testis, or epididymis, or other intrascrotal structures, as well as characterizing lesions as solid or cystic. It is generally assumed that most solid intratesticular masses are more likely malignant, whereas most extratesticular ones are benign, although some exceptions to that rule exist. This pictorial essay will focus on rare and less commonly encountered benign and malignant testicular and paratesticular pathologies, which may pose a diagnostic dilemma for interpreting radiologists and treating physicians. Knowledge of their imaging characteristics will help narrow the differential diagnosis and assist in proper patient management and care.
Sonographic Evaluation of Pelvic Venous Disorders
Authors: Brahmbhatt Akshaar , Macher Jared , Shetty Anisha N. , Chughtai Komal , Baah Nana Ohene , Dogra Vikram S.
Published: September 2021

Pelvic venous disorders are a group of interrelated conditions characterized by venous incompetence. These conditions often manifest with nonspecific symptoms that overlap with many gynecological, gastrointestinal, and urologic diseases. Clinical diagnosis can be difficult, and imaging can play a vital role in differentiating etiology. Sonographic evaluation is often the first step in evaluating these symptoms. Special attention to possible underlying pelvic venous disorders can reveal characteristic findings, support diagnosis, and guide treatment. Here we review pelvic congestion syndrome, nutcracker syndrome, May-Thurner syndrome, and other venous disorders, with a specific focus on sonographic findings and considerations.
Brain–Computer Interfaces in Acute and Subacute Disorders of Consciousness
Authors: Xu Ren , Spataro Rossella , Allison Brendan Z. , Guger Christoph
Published: September 2021

Disorders of consciousness include coma, unresponsive wakefulness syndrome (also known as vegetative state), and minimally conscious state. Neurobehavioral scales such as coma recovery scale—revised are the gold standard for disorder of consciousness assessment. Brain–computer interfaces have been emerging as an alternative tool for these patients. The application of brain–computer interfaces in disorders of consciousness can be divided into four fields: assessment, communication, prediction, and rehabilitation. The operational theoretical model of consciousness that brain–computer interfaces explore was reviewed in this article, with a focus on studies with acute and subacute patients. We then proposed a clinically friendly guideline, which could contribute to the implementation of brain–computer interfaces in neurorehabilitation settings. Finally, we discussed limitations and future directions, including major challenges and possible solutions.
Machine learning methods applied to genotyping data capture interactions between single nucleotide variants in late onset Alzheimer’s disease
Authors: Segura Magdalena Arnal , Orth Dietmar Fernandez , Giambartolomei Claudia , Bini Giorgio , Samaras Eleftherios , Kassis Maya , Aisopos Fotis , De Argila Jordi Rambla , Paliouras Georgios , Garrard Peter , Tartaglia Gian Gaetano
Published: September 2021

INTRODUCTION

Genome-wide association studies (GWAS) in late onset Alzheimer’s disease (LOAD) provide lists of individual genetic determinants. However, GWAS are not good at capturing the synergistic effects among multiple genetic variants and lack good specificity.

METHODS

We applied tree-based machine learning algorithms (MLs) to discriminate LOAD (> 700 individuals) and age-matched unaffected subjects using single nucleotide variants (SNVs) from AD studies, obtaining specific genomic profiles with the prioritized SNVs.

RESULTS

The MLs prioritized a set of SNVs located in close proximity genes PVRL2, TOMM40, APOE and APOC1. The captured genomic profiles in this region showed a clear interaction between rs405509 and rs1160985. Additionally, rs405509 located in APOE promoter interacts with rs429358 among others, seemingly neutralizing their predisposing effect. Interactions are characterized by their association with specific comorbidities and the presence of eQTL and sQTLs.

DISCUSSION

Our approach efficiently discriminates LOAD from controls, capturing genomic profiles defined by interactions among SNVs in a hot-spot region.
Tracking COVID-19 Cases and Deaths in the United States: Distribution of Events by Day of Pandemic
Authors: Moore Andrew , Lyu Mingdong , Hall Randolph
Published: September 2021

In this paper, we analyze the progression of COVID-19 in the United States over a nearly one-year period beginning March 1, 2020, with a novel metric representing the partial-average day-of-event, where events are new cases and new deaths. The metric is calculated as a function of date and location to illustrate patterns of disease, showing growing or waning cases and deaths. The metrics enable the direct comparison of the time distribution of cases and deaths, revealing data coherence and how patterns varied over a one-year period. We also compare different methods of estimating actual infections and deaths to better understand on the timing and dynamics of the pandemic by state. We used three example states to graphically compare metrics as functions of date and also compared statistics derived from all 50 states. Over the period studied, average case day and average death day vary by two to five months among the 50 states, depending on data source, with the earliest averages in New York and surrounding states, as well as Louisiana. The average day of death has preceded the average day of case in Centers for Disease Control (CDC) data for most states and most dates since June of 2020. In contrast, “COVID-19 Projections” more closely align deaths and cases, which are similarly distributed.
DunedinPACE: A DNA methylation biomarker of the Pace of Aging
Authors: Belsky DW , Caspi A , Corcoran DL , Sugden K , Poulton R , Arseneault L , Baccarelli A , Chamarti K , Gao X , Hannon E , Harrington HL , Houts R , Kothari M , Kwon D , Mill J , Schwartz J , Vokonas P , Wang C , Williams B , Moffitt TE
Published: September 2021

Measures to quantify changes in the pace of biological aging in response to intervention are needed to evaluate geroprotective interventions for humans. We used data from the Dunedin Study 1972-3 birth cohort tracking within-individual decline in 19 indicators of organ-system integrity across four time points spanning two decades to model Pace of Aging. We distilled this two-decade Pace of Aging into a single-time-point DNA-methylation blood-test using elastic-net regression and a DNA-methylation dataset restricted to exclude probes with low test-retest reliability. We evaluated the resulting measure, named DunedinPACE, in five additional datasets. DunedinPACE showed high test-retest reliability, was associated with morbidity, disability, and mortality, and indicated faster aging in young adults with childhood adversity. DunedinPACE effect-sizes were similar to GrimAge Clock effect-sizes. In analysis of morbidity, disability, and mortality, DunedinPACE and added incremental prediction beyond GrimAge. DunedinPACE is a novel blood biomarker of the pace of aging for gerontology and geroscience.
Griffin: Framework for clinical cancer subtyping from nucleosome profiling of cell-free DNA
Authors: Doebley Anna-Lisa , Ko Minjeong , Liao Hanna , Cruikshank A. Eden , Kikawa Caroline , Santos Katheryn , Hiatt Joseph , Patton Robert D. , De Sarkar Navonil , Hoge Anna C.H. , Chen Katharine , Weber Zachary T. , Adil Mohamed , Reichel Jonathan , Polak Paz , Adalsteinsson Viktor A. , Nelson Peter S. , Parsons Heather A. , Stover Daniel G. , MacPherson David , Ha Gavin
Published: September 2021

Cell-free DNA (cfDNA) has the potential to inform tumor subtype classification and help guide clinical precision oncology. Here we developed Griffin, a new method for profiling nucleosome protection and accessibility from cfDNA to study the phenotype of tumors using as low as 0.1x coverage whole genome sequencing (WGS) data. Griffin employs a novel GC correction procedure tailored to variable cfDNA fragment sizes, which improves the prediction of chromatin accessibility. Griffin achieved excellent performance for detecting tumor cfDNA in early-stage cancer patients (AUC=0.96). Next, we applied Griffin for the first demonstration of estrogen receptor (ER) subtyping in metastatic breast cancer from cfDNA. We analyzed 254 samples from 139 patients and predicted ER subtype with high performance (AUC=0.89), leading to insights about tumor heterogeneity. In summary, Griffin is a framework for accurate clinical subtyping and can be generalizable to other cancer types for precision oncology applications.
Public-private partnership to rapidly strengthen and scale COVID-19 response in Western Kenya
Authors: van Duijn Shannen , Barsosio Hellen C. , Omollo Mevis , Milimo Emmanuel , Akoth Isdorah , Aroka Robert , de Sanctis Teresa , K’Oloo Alloys , June Micah J. , Houben Nathalie , Wilming Charlotte , Otieno Kephas , Kariuki Simon , Onsongo Simon , Odhiambo Albert , Ganda Gregory , de Wit Tobias F. Rinke
Published: September 2021

INTRODUCTION

In Africa almost half of healthcare services are delivered through private sector providers. These are often underused in national public health responses. In line with our previous HIV experience and to support and accelerate the public sector’s COVID-19 response, we initiated a public-private project (PPP) in Kisumu County, Kenya. In this manuscript we demonstrate this PPP’s performance, using COVID-19 testing as an aggregator and with semi-real time digital monitoring tools for rapid scaling of COVID-19 response.

METHODS

COVID-19 diagnostic testing formed the basis for a PPP between KEMRI, Department of Health Kisumu County, PharmAccess Foundation, and local faith-based and private healthcare facilities: COVID-Dx. COVID-Dx was implemented from June 01, 2020, to March 31, 2021 in Kisumu County, Kenya. Trained laboratory technologists in participating healthcare facilities collected nasopharyngeal and oropharyngeal samples from patients meeting the Kenyan MoH COVID-19 case definition. Samples were rapidly transported by motorbike and tested using RT-PCR at the central reference laboratory in KEMRI. Healthcare workers in participating facilities collected patient clinical data using a digitized MoH COVID-19 Case Identification Form. We shared aggregated results from these data via (semi-) live dashboards with all relevant stakeholders through their mobile phones. Statistical analyses were performed using Stata 16 to inform project processes.

RESULTS

Nine private facilities participated in the project. A detailed patient trajectory was developed from case identification to result reporting, all steps supported by a semi-real time digital dashboard. A total of 4,324 PCR tests for SARS-CoV-2 (16%) were added to the public response, identifying 425 positives. Geo-mapped and time-tagged information on incident cases was depicted on Google maps dashboards and fed back to policymakers for informed rapid decision making. Preferential COVID-19 testing was performed on health workers at risk, with 1,009 tested (43% of all County health workforce).

CONCLUSION

We demonstrate feasibility of rapidly increasing the public health sector response to a COVID-19 epidemic outbreak in an African setting. Our PPP intervention in Kisumu, Kenya was based on a joint testing strategy and demonstrated that semi-real time digitalization of patient trajectories in the healthcare system can gain significant efficiencies, linking public and private healthcare efforts, increasing transparency, support better quality health services and informing policy makers to target interventions. This PPP has since scaled to 33 facilities in Kisumu and subsequently to 84 sites in 14 western Kenyan Counties.
Impairments in goal-directed action and reversal learning in a proportion of individuals with psychosis: evidence for differential phenotypes in early and persistent psychosis
Authors: Suetani Shuichi , Baker Andrea , Garner Kelly , Cosgrove Peter , Mackay-Sim Matilda , Siskind Dan , Murray Graham K , Scott James G , Kesby James P
Published: September 2021

Cognitive impairments in psychosis are one of the strongest predictors of functional decline. Cortico-striatal dysfunction may contribute to both psychosis and cognitive impairment in psychotic illnesses. The decision-making processes underlying goal-directed action and serial reversal learning can be measured and are sensitive to changes reflecting cortico-striatal dysfunction. As such, changes in decision-making performance may assist with predicting functional decline in people with psychosis. We assessed decision-making processes in healthy controls (N=34), and those with early psychosis (N=15) and persistent psychosis (N=45). We subclassified subjects based on intact/impaired goal-directed action. Compared with healthy controls (<20%), a large proportion (58%) of those with persistent psychosis displayed impaired goal-directed action, predicting poor serial reversal learning performance. Computational approaches indicated that those with persistent psychosis were less deterministic in their decision-making. Those with impaired goal-directed action had a decreased capacity to rapidly update their prior beliefs in the face of changing contingencies. In contrast, the early psychosis group included a lower proportion of individuals with impaired goal-directed action (20%) and displayed a different cognitive phenotype from those with persistent psychosis. These findings suggest prominent decision-making deficits, indicative of cortico-striatal dysfunction, are present in a large proportion of people with persistent psychosis while those with early psychosis have relatively intact decision-making processes compared to healthy controls. It is unclear if there is a progressive decline in decision-making processes in some individuals with psychosis or if the presence of decision-making processes in early psychosis is predictive of a persistent trajectory of illness.
The Effective Coverage of Maternal and Child Primary Health Care Services and its Relationship with Health Expenditures: An Analysis at Sub-National Level in Iran
Authors: Abdalmaleki Elham , Abdi Zhaleh , sazgarnejad saharnaz , haghdoost bahar , Ahmadnezhad Elham
Published: September 2021

Backgrounds: Measuring the effective coverage of essential health services is necessary for monitoring progress towards Universal Health Coverage (UHC). So, this study aimed to assess the geographic variations in key maternal and child indicators (as essential health services) provided at the primary health care (PHC) level in terms of their crude and effective coverage, and also to investigate the relationship between the effective coverage and health expenditures in the national and sub-national level of Iran.
Methods: This study was a secondary analysis, which analyzed the spatial distribution of six key maternal and child health indicators using the latest available data of Demographic Health Survey-DHS (2010) across 31 provinces of Iran. Moreover, two composite indicators, the crude, and the effective coverage were calculated. The median cut-off was used to compare provinces situations. Furthermore, the relationship between coverage indicators and total health expenditure per capita was evaluated.
Results: At the national level, the crude and the effective composite coverage were 89.56 and 77.22%, respectively. Also, the medians of composite crude and effective service coverage in the provinces were 90.25 and 77.62%, respectively. There was no significant difference between urban and rural areas.
Conclusions: in this study, we found that there is a significant gap between crude and effective service coverage of the selected indicators. Overall, coverage indicators of maternal services were higher compared to those of children. In addition, geographic variations in key Indicators of maternal and child health services coverage among provinces were almost high. Although the services are free of charge in the rural areas, they did not have higher coverage than those of urban areas. PHC services in Iran are far away from reaching the desired coverage and achieving UHC.
Parameter inference on brain network models with unknown node dynamics and spatial heterogeneity
Authors: Sip Viktor , Petkoski Spase , Hashemi Meysam , Dickscheid Timo , Amunts Katrin , Jirsa Viktor
Published: September 2021

Model-based data analysis of whole-brain dynamics links the observed data to model parameters in a network of neural masses. In recent years a special focus was placed on the role of regional variance of model parameters for the emergent activity. Such analyses however depend on the properties of the employed neural mass model, which is often obtained through a series of major simplifications or analogies. Here we propose a data-driven approach where the neural mass model needs not to be specified. Building on the recent progresses in identification of dynamical systems with neural networks, we propose a method to infer from the functional data both the neural mass model representing the regional dynamics as well as the region- and subject-specific parameters, while respecting the known network structure. We demonstrate on two synthetic data sets that our method is able to recover the original model parameters, and that the trained generative model produces dynamics resembling the training data both on the regional level and on the whole-brain level. We further apply the method to resting-state fMRI data from Human Connectome Project. We find that to achieve best fit, the model needs two dimensional state space and three regional parameters, one of which is strongly correlated with the map of genetic expression in human brain. The present approach opens a novel way to the analysis of resting-state fMRI with possible applications in understanding the changes of whole-brain dynamics during aging or in neurodegenerative diseases.
Gut microbiome and its cofactors are linked to lipoprotein distribution profiles
Authors: Castro-Mejía Josué L. , Khakimov Bekzod , Lind Mads V. , Garne Eva , Paulová Petronela , Tavakkoli Elnaz , Hansen Lars H. , Smilde Age K. , Holm Lars , Engelsen Søren B. , Nielsen Dennis S.
Published: September 2021

Increasing evidence indicates that the gut microbiome (GM) plays an important role in the etiology of dyslipidemia. To date, however, no in-depth characterization of the associations between GM and its metabolic attributes with deep profiling of lipoproteins distributions (LPD) among healthy individuals has been conducted. To determine associations and contributions of GM composition and its cofactors with distribution profiles of lipoprotein subfractions, we studied blood plasma LPD, fecal short-chain fatty acids (SCFA) and GM of 262 healthy Danish subjects aged 19-89 years.

Stratification of LPD segregated subjects into three clusters of profiles that reflected differences in the lipoprotein subclasses, corresponded well with limits of recommended levels of main lipoprotein fractions and were largely explained by host characteristics such as age and body mass index. Higher levels of HDL, particularly driven by large subfractions (HDL2a and HDL2b), were associated with a higher relative abundance of Ruminococcaceae and Christensenellaceae. Increasing levels of total cholesterol and LDL, which were primarily associated with large 1 and 2 subclasses, were positively associated with Lachnospiraceae and Coriobacteriaceae, and negatively with Bacteroidaceae and Bifidobacteriaceae. Metagenome sequencing showed a higher abundance of genes involved in the biosynthesis of multiple B-vitamins and SCFA metabolism among subjects with healthier LPD profiles. Metagenomic assembled genomes (MAGs) affiliated mainly to Eggerthellaceae and Clostridiales were identified as the contributors of these genes and whose relative abundance correlated positively with larger subfractions of HDL.

The results of this study demonstrate that remarkable differences in composition and metabolic traits of the GM are associated with variations in LPD among healthy subjects. Findings from this study provide evidence for GM considerations in future research aiming to shade light on mechanisms of the GM – dyslipidemia axis.
A technique for resolution assessment in blind-SIM experiments
Authors: Boujmil Imen , Xypakis Emmanouil , Ruocco Giancarlo , Leonetti Marco
Published: September 2021

Super resolution techniques are an excellent alternative to wide field microscopy, providing high resolution also in (typically fragile) biological sample. Among the various super resolution techniques, Structured Illumination Microscopy (SIM) improve resolution by employing multiple illumination patterns to be deconvolved with a dedicated software. In the case of blind SIM techniques, unknown patterns, such as speckles, are used, thus providing super resolved images, nearly unaffected by aberrations with a simplified experimental setup. Scattering Assisted Imaging, a special blind SIM technique, exploits an illumination PSF (speckle grains size), smaller than the collection PSF (defined by the collection objectives), to surpass the typical SIM resolution enhancement. However, if SAI is used, it is very difficult to extract the resolution enhancement from a priori considerations. In this paper we propose a protocol and experimental setup for the resolution measurement, demonstrating the resolution enhancement for different collection PSF values.
Absence of cardiolipin from the outer leaflet of a mitochondrial inner membrane mimic restricts Opa1-mediated fusion
Authors: Ge Yifan , Boopathy Sivakumar , Nguyen Tran H , Lugo Camila Makhlouta , Chao Luke H.
Published: September 2021

Cardiolipin is a tetra-acylated di-phosphatidylglycerol lipid enriched in the matrix-facing (inner) leaflet of the mitochondrial inner membrane. Cardiolipin plays an important role in regulating mitochondria function and dynamics. Yet, the mechanisms connecting cardiolipin distribution and mitochondrial protein function remain indirect. In our previous work, we established an in vitro system reconstituting mitochondrial inner membrane fusion mediated by Opa1. We found that the long form of Opa1 (l-Opa1) works together with the proteolytically processed short form (s-Opa1) to mediate fast and efficient membrane fusion. Here, we extend our reconstitution system to generate supported lipid bilayers with asymmetric cardiolipin distribution. Using this system, we find the presence of cardiolipin on the inter-membrane space-facing (outer) leaflet is important for membrane tethering and fusion. We discuss how the presence of cardiolipin in this leaflet may influence protein and membrane properties, and future applications for this approach.
Horizontal mitochondrial transfer from the microenvironment increases glioblastoma tumorigenicity
Authors: Watson Dionysios C. , Bayik Defne , Williford Sarah E. , Lauko Adam , Zhou Yadi , Deshpande Gauravi , Seder Juliana , Mears Jason A. , Cheng Feixiong , Hjelmeland Anita B. , Lathia Justin D.
Published: September 2021

While dynamic microenvironmental interactions drive tumor growth and therapeutic resistance, the underlying direct cell-cell communication mechanisms remain poorly understood. We identified horizontal mitochondrial transfer as a mechanism that enhances tumorigenesis in glioblastoma. This transfer occurs primarily from brain-resident cells, including astrocytes, and can be appreciated in vitro and in vivo through intercellular connections between GBM cells and non-malignant host cells. The acquisition of astrocyte mitochondria drives an overall enhancement of mitochondrial membrane potential and metabolic capacity, while increasing glioblastoma cell self-renewal and tumor-initiating capacity. Collectively, our findings demonstrate that mitochondrial transfer augments the tumorigenic capacity of glioblastoma cells and reveals a previously unknown cell-cell communication mechanism that drives tumor growth.

One-Sentence Summary

Mitochondrial transfer from astrocytes to glioblastoma alters metabolic profile and enhances the tumor-initiation capacity.
Secretory MPP3 reinforce myeloid differentiation trajectory and amplify myeloid cell production
Authors: Kang Yoon-A , Paik Hyojung , Zhang Si Yi , Chen Jonathan , Warr Matthew R. , Fan Rong , Passegué Emmanuelle
Published: September 2021

Recent lineage tracing analyses revealed multipotent progenitors (MPP) to be major functional contributors to steady-state hematopoiesis (1–6). However, we are still lacking a precise resolution of myeloid differentiation trajectories and cellular heterogeneity in MPPs. Here, we found that myeloid-biased MPP3 (2, 3) are functionally and molecularly heterogeneous, with a distinct subset of myeloid-primed secretory cells with high endoplasmic reticulum (ER) volume and FcγR expression. We show that FcγR+/ERhigh MPP3 are a transitional population for rapid production of granulocyte/macrophage progenitors (GMP), which directly amplify myelopoiesis through inflammation-triggered secretion of cytokines in the local bone marrow (BM) microenvironment. Our results identify a novel regulatory function for a subset of secretory MPP3 that controls myeloid differentiation through lineage-priming and cytokine production, and act as a self-reinforcing amplification compartment in stress and disease conditions.

One-Sentence Summary

A secretory subset of multipotent hematopoietic progenitors augment myelopoiesis in stress and diseases conditions.
Riemannian geometry of functional connectivity matrices for multi-site attention-deficit/hyperactivity disorder data harmonization
Authors: Simeon Guillem , Piella Gemma , Camara Oscar , Pareto Deborah
Published: September 2021

The use of multi-site datasets in neuroimaging provides neuroscientists with more statistical power to perform their analyses. However, it has been shown that imaging-site introduces a variability in the data that cannot be attributed to biological sources. In this work, we show that functional connectivity matrices derived from resting-state multi-site data contain a significant imaging-site bias. To this aim, we exploited the fact that functional connectivity matrices belong to the manifold of symmetric positive-definite matrices, making possible to operate on them with Riemannian geometry. We hereby propose a geometry-aware harmonization approach, Rigid Log-Euclidean Translation, that accounts for this site bias. Moreover, we adapted other Riemannian-geometric methods designed for other domain adaptation tasks, and compared them to our proposal. Based on our results, Rigid Log-Euclidean Translation of multi-site functional connectivity matrices seems to be among the studied methods the most suitable one in a clinical setting. This represents an advance with respect to previous functional connectivity data harmonization approaches, which do not respect the geometric constraints imposed by the underlying structure of the manifold. In particular, when applying our proposed method on data from the ADHD-200 dataset, a multi-site dataset built for the study of attention-deficit/hyperactivity disorder, we obtained results that display a remarkable correlation with established pathophysiological findings and, therefore, represent a substantial improvement when compared to the non-harmonization analysis. Thus, we present evidence supporting that harmonization should be extended to other functional neuroimaging datasets, and provide a simple geometric method to address it.
Neural Excursions from Low-Dimensional Manifold Structure Explain Intersubject Variation in Human Motor Learning
Authors: Areshenkoff Corson N. , Gale Dan J. , Nashed Joseph Y. , Standage Dominic , Flanagan J Randall , Gallivan Jason P.
Published: September 2021

Humans vary greatly in their motor learning abilities, yet little is known about the neural mechanisms that underlie this variability. Recent neuroimaging and electrophysiological studies demonstrate that large-scale neural dynamics inhabit a low-dimensional subspace or manifold, and that learning is constrained by this intrinsic manifold architecture. Here we asked, using functional MRI, whether subject-level differences in neural excursion from manifold structure can explain differences in learning across participants. We had subjects perform a sensorimotor adaptation task in the MRI scanner on two consecutive days, allowing us to assess their learning performance across days, as well as continuously measure brain activity. We find that the overall neural excursion from manifold activity in both cognitive and sensorimotor brain networks is associated with differences in subjects’ patterns of learning and relearning across days. These findings suggest that off-manifold activity provides an index of the relative engagement of different neural systems during learning, and that intersubject differences in patterns of learning and relearning across days are related to reconfiguration processes in cognitive and sensorimotor networks during learning.