bluuebunny/crossref_metadata_2025 huggingface dataset:
Current perspectives on wearable rhythm recordings for clinical decision-making: the wEHRAbles 2 survey
Authors: Manninger Martin , Zweiker David , Svennberg Emma , Chatzikyriakou Sofia , Pavlovic Nikola , Zaman Junaid A.B. , Kircanski Bratislav , Lenarczyk Radoslaw , Vanduynhoven Philippe , Kosiuk Jedrzej , Potpara Tatjana , Duncker David
Published: March 2021

Novel wearable devices for heart rhythm analysis using either photoplethysmography (PPG) or electrocardiogram (ECG) are in daily clinical practice. This survey aimed to assess impact of these technologies on physicians’ clinical decision-making and to define, how data from these devices should be presented and integrated into clinical practice. The online survey included 22 questions, focusing on the diagnosis of atrial fibrillation (AF) based on wearable rhythm device recordings, suitable indications for wearable rhythm devices, data presentation and processing, reimbursement, and future perspectives. A total of 539 respondents {median age 38 [interquartile range (IQR) 34–46] years, 29% female} from 51 countries world-wide completed the survey. Whilst most respondents would diagnose AF (83%), fewer would initiate oral anticoagulation therapy based on a single-lead ECG tracing. Significantly fewer still (27%) would make the diagnosis based on PPG-based tracing. Wearable ECG technology is acceptable for the majority of respondents for screening, diagnostics, monitoring, and follow-up of arrhythmia patients, while respondents were more reluctant to use PPG technology for these indications. Most respondents (74%) would advocate systematic screening for AF using wearable rhythm devices, starting at patients’ median age of 60 (IQR 50–65) years. Thirty-six percent of respondents stated that there is no reimbursement for diagnostics involving wearable rhythm devices in their countries. Most respondents (56.4%) believe that costs of wearable rhythm devices should be shared between patients and insurances. Wearable single- or multiple-lead ECG technology is accepted for multiple indications in current clinical practice and triggers AF diagnosis and treatment. The unmet needs that call for action are reimbursement plans and integration of wearable rhythm device data into patient’s files and hospital information systems.
Generic Dynamical Properties of Connections on Vector Bundles
Authors: Cekić Mihajlo , Lefeuvre Thibault
Published: March 2021

Given a smooth Hermitian vector bundle $\mathcal{E}$ over a closed Riemannian manifold $(M,g)$, we study generic properties of unitary connections $\nabla ^{\mathcal{E}}$ on the vector bundle $\mathcal{E}$. First of all, we show that twisted conformal Killing tensors (CKTs) are generically trivial when $\dim (M) \geq 3$, answering an open question of Guillarmou–Paternain–Salo–Uhlmann [ 14]. In negative curvature, it is known that the existence of twisted CKTs is the only obstruction to solving exactly the twisted cohomological equations, which may appear in various geometric problems such as the study of transparent connections. The main result of this paper says that these equations can be generically solved. As a by-product, we also obtain that the induced connection $\nabla ^{\textrm{End}({\operatorname{{\mathcal{E}}}})}$ on the endomorphism bundle $\textrm{End}({\operatorname{{\mathcal{E}}}})$ has generically trivial CKTs as long as $(M,g)$ has no nontrivial CKTs on its trivial line bundle. Eventually, we show that, under the additional assumption that $(M,g)$ is Anosov (i.e., the geodesic flow is Anosov on the unit tangent bundle), the connections are generically opaque, namely that generically there are no non-trivial subbundles of $\mathcal{E}$ that are preserved by parallel transport along geodesics. The proofs rely on the introduction of a new microlocal property for (pseudo)differential operators called operators of uniform divergence type, and on perturbative arguments from spectral theory (especially on the theory of Pollicott–Ruelle resonances in the Anosov case).
Nasopharyngeal Carriage of Streptococcus pneumoniae Among Young Children in Haiti Before Pneumococcal Conjugate Vaccine Introduction
Authors: Francois Watkins Louise K , Milucky Jennifer L , McGee, Lesley , Siné St.-Surin Florence , Liu Pengbo , Tran Theresa , Chochua Sopio , Joseph Gerard , Shang Nong , Juin Stanley , Dely Patrick , Patel Roopal , Van Beneden Chris A
Published: March 2021

Background

Streptococcus pneumoniae, or pneumococcus, is a leading cause of morbidity and mortality in children worldwide. Pneumococcal conjugate vaccines (PCV) reduce carriage in the nasopharynx, preventing disease. We conducted a pneumococcal carriage study to estimate the prevalence of pneumococcal colonization, identify risk factors for colonization, and describe antimicrobial susceptibility patterns among pneumococci colonizing young children in Port-au-Prince, Haiti, before introduction of 13-valent PCV (PCV13).

Methods

We conducted a cross-sectional study of children aged 6–24 months at an immunization clinic in Port-au-Prince between September 2015 and January 2016. Consenting parents were interviewed about factors associated with pneumococcal carriage; nasopharyngeal swabs were collected from each child and cultured for pneumococcus after broth enrichment. Pneumococcal isolates were serotyped and underwent antimicrobial susceptibility testing. We compared frequency of demographic, clinical, and environmental factors among pneumococcus-colonized children (carriers) to those who were not colonized (noncarriers) using unadjusted bivariate analysis and multivariate logistic regression.

Results

Pneumococcus was isolated from 308 of the 685 (45.0%) children enrolled. Overall, 157 isolates (50.8%) were PCV13 vaccine-type serotypes; most common were 6A (13.3%), 19F (12.6%), 6B (9.7%), and 23F (6.1%). Vaccine-type isolates were significantly more likely to be nonsusceptible to ≥1 antimicrobial (63.1% vs 45.4%, P = .002). On bivariate analysis, carriers were significantly more likely than noncarriers to live in a household without electricity or running water, to share a bedroom with ≥3 people, to have a mother or father who did not complete secondary education, and to have respiratory symptoms in the 24 hours before enrollment (P < .05 for all comparisons). On multivariable analysis, completion of the pentavalent vaccination series (targeting diphtheria, pertussis, tetanus, hepatitis B, and Haemophilus influenzae type b) remained significantly more common among noncarriers.

Conclusions

Nearly a quarter of healthy children surveyed in Haiti were colonized with vaccine-type pneumococcal serotypes. This baseline carriage study will enable estimation of vaccine impact following nationwide introduction of PCV13.
Deployment and testing of an automated medical equipment service communication and documentation system at a rural hospital in Kenya
Authors: Gordon Rayonna M , Saldana Santiago J , Brown Philip J , Gayzik F Scott , Anthony Evelyn Y
Published: March 2021

Background

The Medical Equipment Network Documentation System (MENDS) provides a simple communication network for equipment servicing from failure to restoration. It is a text messaging-based platform, designed to use existing technologies in place in low- and middle-income settings. The system gathers and relays information about equipment service requests and reports and automatically saves them to an online database.

Methods

MENDS was deployed at a high volume, rural, charity medical facility in Kijabe, Kenya for a 3-mo pilot test.

Results

The results show MENDS more than tripled documentation and enhanced ease and speed of communication.

Conclusions

Comprehensive data provided by MENDS created more accurate measures of equipment performance, which can be used to decrease the time that equipment is out of service and improve the efficiency of repairs, equipment quality and procurement.
Role of the high-affinity reductive iron acquisition pathway of Candida albicans in prostaglandin E2 production, virulence, and interaction with Pseudomonas aeruginosa
Authors: Mochochoko Bonang M , Ezeokoli Obinna T , Sebolai Olihile , Albertyn Jacobus , Pohl Carolina H
Published: March 2021

Components of the iron reductive pathway of Candida albicans have been implicated in the production of prostaglandin E2 (PGE2) and virulence. However, it is unknown whether other components of this pathway influence PGE2. We investigated the role of the iron reductive pathway of C. albicans in biofilm formation, PGE2 production, and virulence in Caenorhabditis elegans. Additionally, as the co-occurrence of C. albicans and Pseudomonas aeruginosa in host tissues is frequent and involves competition for host-associated iron, we examined the effects of this interaction. Deletion of multicopper oxidase gene, FET99, and iron permease genes, FTH1 and FTH2, affected biofilm metabolic activity, and for the FTH2 mutant, also biofilm morphology. Deletion of CCC1 (vacuolar iron transporter) and CCC2 (P-type ATPase copper importer) also influenced biofilm morphology. For PGE2 production, deletion of FET99, FTH1, FTH2, CCC1, and CCC2 caused a significant reduction by monomicrobial biofilms, while FTH2deletion caused the highest reduction in polymicrobial biofilms. URA3 positive mutants of FET99 and FTH2 demonstrated attenuated virulence in C. elegans, potentially due to the inability of mutants to form hyphae in vivo. Deductively, the role of the iron reductive pathway in PGE2 synthesis is indirect, possibly due to their role in iron homeostasis.

Lay Summary

Iron uptake is vital for disease-causing microbes like Candida albicans. Using strains deficient in some iron-uptake genes, we show that iron-uptake genes, especially FET99 and FTH2, play a role in biofilm formation, prostaglandin production, and virulence in the nematode infection model.
Implementation of Individualized Pain Care Plans Decreases Length of Stay and Hospital Admission Rates for High Utilizing Adults with Sickle Cell Disease
Authors: Welch-Coltrane Jena L , Wachnik Anthony A , Adams Meredith C B , Avants Cherie R , Blumstein Howard A , Brooks Amber K , Farland Andrew M , Johnson Joshua B , Pariyadath Manoj , Summers Erik C , Hurley Robert W
Published: March 2021

Objective

Patients with sickle cell disease (SCD) face inconsistent effective analgesic management, leading to high inpatient healthcare utilization and significant financial burden for healthcare institutions. Current evidence does not provide guidance for inpatient management of acute pain in adults with sickle cell disease. We conducted a retrospective analysis of a longitudinal cohort quality improvement project to characterize the role of individualized care plans on improving patient care and reducing financial burden in high healthcare-utilizing patients with SCD-related pain.

Methods

Individualized care plans were developed for patients with hospital admissions resulting from pain associated with sickle cell disease. A 2-year prospective longitudinal cohort quality improvement project was performed and retrospectively analyzed. Primary outcome measure was duration of hospitalization. Secondary outcome measures included: pain intensity; 7, 30, and 90-day readmission rates; cost per day; total admissions; total cost per year; analgesic regimen at index admission; and discharge disposition.

Results

Duration of hospitalization, the primary outcome, significantly decreased by 1.23 days with no worsening of pain intensity scores. Seven-day readmission decreased by 34%. Use of intravenous hydromorphone significantly decreased by 25%. The potential cost saving was $1,398,827 as a result of this quality initiative.

Conclusions

Implementation of individualized care plans reduced both admission rate and financial burden of high utilizing patients. Importantly, pain outcomes were not diminished. Results suggest that individualized care plans are a promising strategy for managing acute pain crisis in adult sickle cell patients from both care-focused and utilization outcomes.
Toward physician well-being and the mitigation of burnout
Authors: Janosy Norah R. , Anderson Corrie T.M.
Published: March 2021

Purpose of review

Healthcare provider burnout is a real phenomenon. The rates of burnout are on the rise. Burnout-associated suicide amongst physicians represents a real “public health crisis.” This article discusses the drivers of burnout and offers some strategies to mitigate burnout and improve well-being.

Recent findings

Measures of burnout such as stress, micro, and macro-aggression in the workplace have a psychological impact on staff. Additionally, a measurable economic price is exacted when an organization fails to address the lack of well-being burnout represents.

As healthcare providers struggle to survive and deal with the complex new set of problems and obstacles that the COVID-19 pandemic, the National economic crisis, and the increasing regulatory obligations have summoned forth, professional burnout rates have risen drastically. With good leadership, developing comprehensive programs to identify, track, and treat burnout symptoms and improve well-being in the work environment can result in greater work satisfaction and save resources.
Reinstating Elective Surgeries in MedStar Health
Authors: Stein David E. , Chia Stanley H. , Breakey Thomas H. , Song David H. , Woo Edward Y. , Fairbanks Rollin J. , Jordan David , Curl Leigh Ann , Boucher Henry R. , Boyle Lisa , Edwards Karol , Friedrich Hanna , Gilbert Robert J. , Matton Jeffrey , Mucci Kathy , Chambers Bradley , Sachtleben Michael , Watson Thomas J.
Published: March 2021

Introduction:

Coronavirus disease 2019 (COVID-19) infections have strained hospital resources worldwide. As a result, many facilities have suspended elective operations and ambulatory procedures. As the incidence of new cases of COVID-19 decreases, hospitals will need policies and algorithms to facilitate safe and orderly return of normal activities. We describe the recommendations of a task force established in a multi-institutional healthcare system for resumption of elective operative and ambulatory procedures applicable to all hospitals and service lines.

Methods:

MedStar Health created a multidisciplinary task force to develop guidelines for resumption of elective surgeries/procedures. The primary focus areas included the establishment of a governance structure at each healthcare facility, prioritization of elective cases, preoperative severe acute respiratory syndrome coronavirus 2 testing, and an assessment of the needs and availability of staff, personal protective equipment, and other essential resources.

Results:

Each hospital president was tasked with establishing a local perioperative leadership team answering directly to them and granted the authority to prioritize elective surgery and ambulatory procedures. An elective surgery algorithm was established using a simplified Medically Necessary Time Sensitive score, with multiple steps requiring a “go/no-go” assessment based on local resources. In addition, mandatory preoperative COVID testing policies were developed and operationalized.

Conclusions:

Even when the COVID pandemic has passed, hospitals and surgical centers will require COVID screening and testing, case prioritization, and supply chain management to provide care essential to the surgical patient while protecting their safety and that of staff. Our guidelines consider these factors and are applicable to both tertiary academic medical centers and smaller community facilities.
Quasi-Contextualized Speech Treatment in Traumatic Brain Injury Inpatient Rehabilitation: Effects on Outcomes During the First Year After Discharge
Authors: Beaulieu Cynthia L. , Peng Juan , Hade Erinn M. , Montgomery Erin , Gilchrist Kamie , Corrigan John D. , Horn Susan D. , Bogner Jennifer
Published: March 2021

Objective:

To evaluate the effect of providing quasi-contextualized speech therapy, defined as metacognitive, compensatory, or strategy training applied to cognitive and language impairments to facilitate the performance of future real-life activities, on functional outcomes up to 1 year following traumatic brain injury (TBI).

Setting:

Acute inpatient rehabilitation.

Participants:

Patients enrolled during the TBI-Practice-Based Evidence (TBI-PBE) study (n = 1760), aged 14 years or older, who sustained a severe, moderate, or complicated mild TBI, received speech therapy in acute inpatient rehabilitation at one of 9 US sites, and consented to follow-up 3 and 9 months postdischarge from inpatient rehabilitation.

Design:

Propensity score methods applied to a database consisting of multisite, prospective, longitudinal observational data.

Main Measures:

Participation Assessment with Recombined Tools-Objective-17, FIM Motor and Cognitive scores, Satisfaction With Life Scale, and Patient Health Questionnaire-9.

Results:

When at least 5% of therapy time employed quasi-contextualized treatment, participants reported better community participation during the year following discharge. Quasi-contextualized treatment was also associated with better motor and cognitive function at discharge and during the year after discharge. The benefit, however, may be dependent upon a balance of rehabilitation time that relied on contextualized treatment.

Conclusions:

The use of quasi-contextualized treatment may improve outcomes. Care should be taken, however, to not provide quasi-contextualized treatment at the expense of contextualized treatment.
Change in Learning and Memory Partially Mediates Effects of Compensatory Cognitive Training on Self-Reported Cognitive Symptoms
Authors: O'Neil Maya Elin , Cameron David , Shirley Kate , Sano Emily , Twamley Elizabeth , Williams Rhonda , Turner Aaron , Pagulayan Kathleen , Roost Mai , Jak Amy , Storzbach Daniel , Huckans Marilyn
Published: March 2021

Objective:

To examine associations among compensatory cognitive training (CCT), objective cognitive functioning, and self-reported cognitive symptoms. We examined whether change in objective cognitive functioning associated with participation in CCT at 10-week follow-up mediates change in self-reported cognitive symptoms associated with CCT at 15-week follow-up.

Setting:

Three VA outpatient mental health clinics.

Participants:

Veterans with a history of mild traumatic brain injury who reported cognitive deficits.

Design:

Randomized controlled trial post hoc causal mediation analysis.

Main Measures:

Self-reported cognitive symptoms were measured by the Prospective-Retrospective Memory Questionnaire and the Multiple Sclerosis Neuropsychological Screening Questionnaire. Objective cognitive functioning was measured using a battery of neuropsychological tests.

Results:

Improvement on the Hopkins Verbal Learning Test—Revised (HVLT-R) Delayed Recall test mediated the association between participation in CCT and decrease in the Prospective-Retrospective Memory Questionnaire total score. Improvement on the HVLT-R Total Recall and HVLT-R Delayed Recall tests both meditated the association between participation in CCT and decrease in the Multiple Sclerosis Neuropsychological Screening Questionnaire total score. No other measures of objective cognitive functioning were significant mediators.

Conclusion:

Patients' perceptions of cognitive symptom improvement due to CCT are partially mediated by learning and memory, though these subjective improvements occur regardless of other changes in objective cognitive functioning associated with CCT.
In-vivo imaging of the conventional aqueous outflow system
Authors: Lee Daniel , Kolomeyer Natasha N. , Razeghinejad Reza , Myers Jonathan S.
Published: March 2021

Purpose of review

The aim of this study was to provide a comprehensive summary of in-vivo imaging techniques of the aqueous outflow system and discuss its role in improving our understanding of glaucoma pathogenesis and management.

Recent findings

Our understanding of the aqueous outflow system is largely derived from ex-vivo studies. Recent innovations in imaging technology and techniques enable in-vivo evaluation of the conventional outflow system in real-time. Optical coherence tomography allows for noninvasive, high-resolution, volumetric imaging of ocular tissues. Dynamic structural changes have been observed at the trabecular meshwork and Schlemm's canal. In parallel, aqueous angiography using injected tracers show a similar dynamism with variable and pulsatile flow signals.

In-vivo imaging enable real-time evaluation of the conventional aqueous outflow pathway. This emerging field shows great promise to expand our understanding of the pathogenesis and treatment of glaucoma.
A Review of the State of the Science of HIV and Stigma: Context, Conceptualization, Measurement, Interventions, Gaps, and Future Priorities
Authors: Relf Michael V. , L. Holzemer William , Holt Lauren , Nyblade Laura , Ellis Caiola Courtney
Published: March 2021

Stigma is a fundamental cause of health inequities. As such, stigma is a major barrier to HIV prevention, care, and treatment. This review will examine the concept of stigma, explicating the mechanisms of action of HIV-related stigma while also examining intersectional stigma and structural stigma. Instruments to measure HIV-related stigma and its mechanisms of action, as well as stigma enacted and experienced by HIV health care providers, will also be reviewed. This article will conclude with a review of stigma interventions, gaps in the literature, and priorities for future HIV, intersectional, and structural stigma research.
A homozygous loss-of-function mutation in GP1BB causing variable clinical phenotypes in a family with Bernard–Soulier syndrome
Authors: Al-Numair Nouf , Ramzan Khushnooda , Alquait Laila , Alshehri Meshal , Imtiaz Faiqa , Owaidah Tarek
Published: March 2021

Bernard–Soulier syndrome is a rare autosomal recessive bleeding disorder and has a low incidence. Bernard–Soulier syndrome is caused by the deficiency of glycoprotein GPIb-V-IX complex, a receptor for von Willebrand factor and is characterized by thrombocytopenia, giant platelets and bleeding tendency. We are reporting three members of a same family with variable phenotypic clinical presentation. The index case is a 20-year-old boy who has a frequent presentation with epistaxis, and low platelet counts (25 × 109/l). He had been hospitalized multiple times and received platelet transfusions. His brother and cousin reported bleeding symptoms with less frequent medical intervention. Genetic analysis by next-generation sequencing identified a homozygous GP1BB variant (c.423C>A:p.Cys141Ter), which segregated amongst the family members. The results led us to an improved insight into the disease for this family with variable phenotypic expression, in addition to the identification of a variant for further structural and functional characterization.
Impact of the COVID-19 pandemic on physical activity, anxiety, and depression in patients with Parkinson’s disease
Authors: Balci Birgul , Aktar Burcin , Buran Sinan , Tas Melike , Donmez Colakoglu Berril
Published: March 2021

The coronavirus disease 2019 pandemic has yielded containment measures with detrimental effects on the physical and mental health of the general population. The impacts of lockdown on clinical features in Parkinson’s disease are not well known. We aimed to compare the physical activity, anxiety–depression levels between Parkinson’s disease patients and controls during lockdown. Forty-five Parkinson’s disease patients and 43 controls were evaluated with the Physical Activity Scale for the Elderly (PASE) and Hospital Anxiety and Depression Scale (HADS) via telephone interview. The patients’ disease-related symptoms were worsened during lockdown though regular Parkinson’s disease medication use. The PASE scores were low in both groups. The HADS scores of groups were below the cutoff point of anxiety–depression presence. Pandemic restrictions could lead to worsening of the motor and nonmotor symptoms in Parkinson’s disease.
Serine/Threonine Kinase 11 Plays a Canonical Role in Malignant Progression of KRAS-Mutant and GNAS-Wild-Type Intraductal Papillary Mucinous Neoplasms of the Pancreas
Authors: Omori Yuko , Ono Yusuke , Morikawa Takanori , Motoi Fuyuhiko , Higuchi Ryota , Yamamoto Masakazu , Hayakawa Yuko , Karasaki Hidenori , Mizukami Yusuke , Unno Michiaki , Furukawa Toru
Published: March 2021

Objective:

We aimed to elucidate the clinicopathobiological significance of Serine/Threonine Kinase 11 (STK11) in pancreatic intraductal papillary mucinous neoplasms (IPMNs).

Background:

STK11 is a tumor suppressor involved in certain IPMNs; however, its significance is not well known.

Methods:

In 184 IPMNs without Peutz-Jeghers syndrome, we analyzed expression of STK11 and phosphorylated-AMPKa in all cases, and p16, p53, SMAD4, and β-catenin in 140 cases by immunohistochemistry; and we analyzed mutations in 37 genes, including whole coding exons of STK11, CDKN2A, TP53, and SMAD4, and hotspots of KRAS, BRAF, and GNAS in 64 cases by targeted sequencing. KRAS and GNAS were additionally analyzed in 86 STK11-normal IPMNs using digital-PCR.

Results:

Consistent loss or reduction of STK11 expression was observed in 26 of 184 (14%) IPMNs. These STK11-aberrant IPMNs were 17 of 45 (38%) pancreatobiliary, 8 of 27 (30%) oncocytic, 1 of 54 (2%) gastric, and 0 of 58 (0%) intestinal subtypes (P = 8.5E-11), and 20 of 66 (30%) invasive, 6 of 74 (8%) high-grade, and 0 of 44 (0%) low-grade (P = 3.9E-06). Sixteen somatic STK11 mutations (5 frameshift, 6 nonsense, 1 splicing, and 4 missense) were detected in 15/26 STK11-aberrant IPMNs (P = 4.1E-06). All STK11-aberrant

IPMNs were GNAS-wild-type and 96% of them were KRAS or BRAF-mutant.

Morphologically, STK11-aberrant IPMNs presented “fern-like” arborizing papillae with thin fibrovascular core. Phosphorylated-AMPKa was down-regulated in STK11-aberrant IPMNs (92%, P = 6.8E-11). Patients with STK11-aberrant IPMNs showed poorer survival than patients with STK11-normal IPMNs (P = 3.6E-04 overall; P = 6.1E-04 disease-free).

Conclusion:

STK11 may play a canonical role in malignant progression and poor survival of patients with IPMNs. Aberrant STK11-driven phosphorylated AMPK downregulation may provide therapeutic opportunities with mTOR inhibitors/AMPK activators.
Attrition From a National Surgical Training Program
Authors: Nally Deirdre M. , Kavanagh Dara , Traynor Oscar , Bennett Deirdre
Published: March 2021

Objective:

The objective of this study was to examine the trainee experience to identify some of the factors which contribute to attrition from surgical training.

Summary Background:

Not all trainees who commence a surgical training program continue and complete it. Surgical training can be personally and professionally demanding and trainees may, for a multitude of reasons, change career direction. Attrition from surgical training impacts upon multiple stakeholders: A decision to leave may be difficult and time consuming for the individual and can generate unanticipated inefficiency at a systems level. This project examined attrition from a national surgical training program to deepen understanding of some of the causes of the phenomenon.

Methods:

A qualitative study was performed. A purposeful sampling strategy was used to identify representative participants. Semistructured interviews were conducted with eleven trainees who withdrew or considered doing so. A thematic analysis was performed to examine the experiences of trainees and explore the factors which influenced a decision to withdraw.

Findings:

Five major themes emerged from the interview data: delivery of training, the training atmosphere, influence of seniors, concerns regarding progression, and the perception of the future role with respect to lifestyle.

Conclusions:

The personal experience of surgical training is crucial in informing a decision to withdraw from a program. Voluntary attrition is appropriate where doctors, after experiencing some time in surgical training, recognize that a surgical career does not meet their expectation. However, improving the delivery of training by addressing the concerns identified in this study may serve to enhance the personal training experience and hence maximize retention.
High mobility group box 1 promotes the differentiation of spinal ependymal cells into astrocytes rather than neurons
Authors: Zhang Hongyan , Liu Jingjing , Ling Chengming , Chen Xin , Lin Jiangkai , Feng Hua , Chu Weihua
Published: March 2021

Spinal ependymal cells are involved in proliferation, differentiation and migration after spinal cord injury (SCI) and represent an endogenous source of repair cells for treating SCI. However, 95% of activated ependymal cells eventually differentiate into astrocytes after SCI and ultimately contribute more than half of the new astrocytes that form glial scars in vivo. The factors that regulate the fate of ependymal cells after SCI remain unclear. High mobility group box 1 (HMGB1) is regarded as an important proinflammatory factor in nerve injury, and recent studies have shown that HMGB1 can regulate the fate of stem cells after injury. In this study, we investigated whether HMGB1 released from reactive astrocytes after SCI regulates the proliferation and differentiation of ependymal cells in vitro. Ependymal cells extracted and cultured from the spinal cord of mice were separately treated with astrocyte culture medium (ACM), IL-1β, ACM (IL-1β) and the HMGB1 protein, and the proliferation and differentiation of ependymal cells were detected. Additionally, an HMGB1-neutralizing antibody (anti-HMGB1) was added to further verify the regulatory effect of HMGB1 on ependymal cells. The results showed that HMGB1 released from reactive astrocytes promoted ependymal cell differentiation into astrocytes and inhibited ependymal cell differentiation into neurons in vitro; however, the effect disappeared after the addition of anti-HMGB1. HMGB1 had no significant effect on ependymal cell proliferation. Our findings demonstrate that HMGB1 can regulate the differentiation of ependymal cells after SCI. These results provide a new strategy for the treatment of SCI.
Intracerebral hemorrhage influences hippocampal neurogenesis and neurological function recovery via Notch1 signaling
Authors: Chen Jing , Yuan Xing-Yun , Zhang Xu
Published: March 2021

Intracerebral hemorrhage (ICH) is associated with high rate of mortality and morbidity, but lacks effective therapies. Accumulating studies indicated that the hippocampal neurogenesis plays an essential role in the recovery of neurological function after ICH. The Notch1 signaling pathway shows important roles in neurogenesis. However, the effects of Notch1 on the recovery of neurological function after ICH remain unclear. Here, we used ICH mice model to investigate whether Notch1 signaling was involved in the hippocampal neurogenesis and the recovery of neurological function post-ICH. Our results showed that the rate of symmetric division pattern of hippocampal neural stem cells (NSCs) decreased significantly at 3 days after ICH. Meanwhile, the expression of Notch1 in the hippocampus also was reduced significantly. However, Notch1 activator treatment enhanced the expression of Notch1 and increased the number of Sox2+GFAP+ cells. Further, the rate of symmetric division pattern of NSCs also increased after Notch1 activator treatment in mice with ICH. Importantly, the number of DCX+ cells and BrdU+NeuN+ in hippocampus were increased on 28 days post-ICH as the Notch1 expression was upregulated. The motor function and spatial memory ability in post-ICH mice following Notch1 activator treatment also were improved. Taken together, our results suggested that Notch1 signaling could influence the recovery of long-term neurological function by regulating the proliferation and differentiation of the hippocampal NSCs in mice after ICH. Our study may provide ideas for the improvement of neurological function and spatial memory defects after ICH.
Abnormal intrinsic functional network hubs in diabetic retinopathy patients
Authors: Huang Xin , Xie Bao-Jun , Qi Chen-Xing , Tong Yan , Shen Yin
Published: March 2021

Background

However, whether the whole-brain functional network hub changes occur in diabetic retinopathy patients remains unknown.

Purpose

The purpose of the study was to investigate the function network centrality and connectivity changes in diabetic retinopathy patients using the voxel-wise degree centrality method.

Materials and methods

Thirty-four diabetic retinopathy patients (18 male and 16 female) and 38 healthy controls (18 male and 20 female) closely matched in age, sex, and education were enrolled in the study. Graph theory-based network analysis was performed to investigate the degree centrality between two groups.

Results

Compared with healthy controls, diabetic retinopathy patients had significantly higher degree centrality values in the pons and bilateral caudate and had significantly lower degree centrality values in the left lingual and right lingual, and right angular/middle occipital gyrus (MOG). Moreover, diabetic retinopathy patients exhibited increased functional connectivity between the bilateral lingual and right cerebellum lobe and right fusiform/bilateral caudate and increased functional connectivity between the right angular/MOG and bilateral anterior cingulum and right cuneus/bilateral precuneus and increased functional connectivity between the bilateral caudate and right lingual and right superior occipital gyrus. In contrast, diabetic retinopathy patients showed decreased functional connectivity between bilateral lingual and left lingual and right lingual and left superior occipital gyrus and decreased functional connectivity between the angular/MOG and right inferior occipital gyrus/right fusiform and left MOG/inferior occipital gyrus and decreased functional connectivity between the bilateral caudate and bilateral cerebellum crus1.

Conclusion

Our results highlight that reorganization of the hierarchy of the cortical connectivity network related to visual network.
Age-related changes in expression of lysine48 and lysine63 ubiquitin linkages in dopamine neurons of midbrain in mice
Authors: Jiang Jing , Hu Xiujuan , Liu Lihua , He Zhicheng , Wu Qingjie , Li Qunchao , Hu Xianwei , Jiang Nan , Liu Chao
Published: March 2021

Ubiquitination of target proteins is mediated via different ubiquitin lysine (K) linkages and determines the protein fates. In particular, K48 ubiquitin linkage targets proteins for degradation, whereas K63 ubiquitin linkage plays a nondegradative role. Parkinson’s disease is an age-onset neurodegenerative disorder, which shows selective loss of dopamine neurons in substantia nigra pars compacta (SNC) and ubiquitinated protein aggregates. However, age-related expression of K48 and K63 ubiquitin linkages in SNC dopamine neurons remains elusive. We thus sought to explore the expression of K48 and K63 ubiquitin linkages in dopamine neurons in SNCs of mice at different ages with morphological and biochemical assays. Here our results indicated that in 5-week-old mice, dopamine neurons presented higher levels of K48 and K63 ubiquitin linkages than nondopamine neural cells. Aging promoted the formation of protein aggregates that are positive for both K48 and K63 ubiquitin linkages, together with tyrosine hydroxylase, a dopamine neuron marker. Moreover, 21-month-old mice showed fewer neural cells and tyrosine hydroxylase positive neurons in the SNCs than younger mice. Through biochemical analysis, the 21-month-old mice were shown to express more K48 ubiquitin linkages and less tyrosine hydroxylase and NeuN than the 5-week-old mice. These results suggest the first time that expression of K48 and K63 ubiquitin lysine linkages in midbrain dopamine neurons is age-related and may be involved in the loss of dopamine neurons.
Mind the step: did Hooker's judgement clinch Darwin's disenchantment?
Authors: Partridge Derek
Published: March 2021

The decade from 1844 to 1854 in which Charles Darwin first published two books and then studied barnacles for the final eight years has long been a puzzling digression from the development of his theory of evolution. This essay proposes that it was a conjunction of two quite different activities: a three-year pause initiated to assess and hopefully finalize the editorial completion of his 1844 Essay for publication, followed by a step-change decision to redirect his primary research activity in late 1847. A disenchantment hypothesis is proposed; it presents the step-change decision as a consequence of weighing up the accumulated unencouraging prospects for species-theory development in competition with the emergence of promising projections associated with a broad study of marine invertebrates. Recognition of the triumph, as Darwin initially saw it, of his Essay, followed by years of hostile inputs, opens this new route to understanding this decade. Within it Joseph Hooker emerges as a significant causal force. Many of the customary ‘postponement’ explanations of this digression can be integrated with this pause-and-step-change explanation, whereas explanation of the interval as a gap due to a pre-planned activity cannot, and is revealed to be seriously faulty.
Management Algorithm of External Fixation in Lower Leg Arterial Injury for Limb Salvages
Authors: Jin Lei , Zhang Song , Liu Motao , Zhang Yuxuan , Lin Xin , Feng Dehong , Hu Kejia
Published: March 2021

Purpose

The purpose of this study was to review the roles of using external fixation to rescue the patients who sustained arterial injuries in the lower legs.

Methods

Demographics, surgical treatment and outcomes in 88 patients with lower leg arterial injuries treated by external fixation at two trauma centers from 2009 to 2018 were reviewed. The primary outcome was the rate of successful lower leg salvage, while secondary outcomes were complications and functional recovery.

Results

80 patients (90 legs) maintained a successful lower leg salvage. The patients were followed up for an average of 15.5±5.5 months. 6 patients (8 pins) experienced pin-tract infection, pins loosening happened in 2 patients (4 pins), 7 patients (7 legs) developed wound superficial infection, 3 patients (3 legs) with a deep infection developed osteomyelitis, 16 patients (17 legs) suffered the bone nonunion or bone defect. The average healing time of fracture was 5.6±4.3months. The maintain of external fixation average time was 5.8±3.6 months.

Conclusion

With correctly judging the condition of limb ischemia, mastering reasonably the operation indications, and preventing complications, good clinical effects can be achieved when external fixation is used.

Level of evidence

Retrospective cohort, level IV.
Contextual Embeddings from Clinical Notes Improves Prediction of Sepsis
Authors: Amrollahi Fatemeh , P. Shashikumar Supreeth , Razmi Fereshteh , Nemati Shamim
Published: March 2021

Sepsis, a life-threatening organ dysfunction, is a clinical syndrome triggered by acute infection and affects over 1 million Americans every year. Untreated sepsis can progress to septic shock and organ failure, making sepsis one of the leading causes of morbidity and mortality in hospitals. Early detection of sepsis and timely antibiotics administration is known to save lives. In this work, we design a sepsis prediction algorithm based on data from electronic health records (EHR) using a deep learning approach. While most existing EHR-based sepsis prediction models utilize structured data including vitals, labs, and clinical information, we show that incorporation of features based on clinical texts, using a pre-trained neural language representation model, allows for incorporation of unstructured data without an explicit need for ontology-based named-entity recognition and classification. The proposed model is trained on a large critical care database of over 40,000 patients, including 2805 septic patients, and is compared against competing baseline models. In comparison to a baseline model based on structured data alone, incorporation of clinical texts improved AUC from 0.81 to 0.84. Our findings indicate that incorporation of clinical text features via a pre-trained language representation model can improve early prediction of sepsis and reduce false alarms.
Cholecystokinin Suppresses β-Cell Apoptosis, Including in Human Islets in a Transplant Model
Authors: Kim Hung Tae , de Souza Arnaldo H. , Umhoefer Heidi , Han JeeYoung , Anzia Lucille , Sacotte Steven J. , Williams Rashaun A. , Blumer Joseph T. , Bartosiak Jacob T. , Fontaine Danielle A. , Baan Mieke , Kibbe Carly R. , Davis Dawn Belt
Published: March 2021

Loss of functional pancreatic β-cell mass and increased β-cell apoptosis are fundamental to the pathophysiology of both type 1 and type 2 diabetes. Pancreatic islet transplantation has the potential to cure type 1 diabetes but is often ineffective due to the death of the islet graft within the first few years after transplant. Therapeutic strategies to directly target pancreatic β-cell survival are needed to prevent and treat diabetes and to improve islet transplant outcomes. Reducing β-cell apoptosis is also a therapeutic strategy for type 2 diabetes. Cholecystokinin (CCK) is a peptide hormone typically produced in the gut after food intake, with positive effects on obesity and glucose metabolism in mouse models and human subjects. We have previously shown that pancreatic islets also produce CCK. The production of CCK within the islet promotes β-cell survival in rodent models of diabetes and aging. Now, we demonstrate a direct effect of CCK to reduce cytokine-mediated apoptosis in a β-cell line and in isolated mouse islets in a receptor-dependent manner. However, whether CCK can protect human β-cells was previously unknown. Here, we report that CCK can also reduce cytokine-mediated apoptosis in isolated human islets and CCK treatmentin vivodecreases β-cell apoptosis in human islets transplanted into the kidney capsule of diabetic NOD/SCID mice. Collectively, these data identify CCK as a novel therapy that can directly promote β-cell survival in human islets and has therapeutic potential to preserve β-cell mass in diabetes and as an adjunct therapy after transplant.

One Sentence Summary

Cholecystokinin ameliorates pancreatic β-cell death under models of stress and after transplant of human islets.
ipyChord: a package for evaluating small-angle X-ray scattering data of fiber symmetry
Authors: Li Xuke
Published: March 2021

This article presents a Python-based package, ipyChord, to compute the 2D chord distribution function (CDF) from the small-angle X-ray scattering (SAXS) pattern from polymer materials with fiber-symmetrical nanostructure. The program allows construction of a harmonized SAXS pattern from a raw SAXS pattern, by normalization of the incident-beam intensity, absorption correction for sample thickness, masking blind areas on the detector, and filling in the shadow of the beamstop and its holder using symmetry operations. Patterns from modular detectors with inter-module gaps can still be fully constructed satisfactorily after determining the optimized beam position and a radial basis function. A CDF pattern computed from the full SAXS pattern can be used to determine the domain size and its variability using a graphical method. An interface distribution function computed from Bonart's longitudinal projection or sliced from a CDF meridian can quantify differently stacked hard and soft domains. Two cases of the application of ipyChord are presented. The software is open source and available at https://github.com/isaxs/ipyChord.
Process modeling for smart factories: using science mapping to understand the strategic themes, main challenges and future trends
Authors: Sott Michele Kremer , Furstenau Leonardo B. , Kipper Liane Mahlmann , Reckziegel Rodrigues Yan Pablo , López-Robles José Ricardo , Giraldo Fáber D. , Cobo Manuel J.
Published: March 2021

Purpose

The purpose of this paper is to identify the relationships between process modeling and Industry 4.0, the strategic themes and the most used process modeling language in smart factories. The study also presents the growth of the field of study worldwide, the perspectives, main challenges, trends and suggestions for future works.

Design/methodology/approach

To do this, a science mapping was performed using the software SciMAT, supported by VOS viewer.

Findings

The results show that the Business Process Model and Notation (BPMN), Unified Modelling Language (UML) and Petri Net are the most relevant languages to smart manufacturing. The authors also highlighted the need to develop new languages or extensions capable of representing the dynamism, interoperability and multiple technologies of smart factories.

Originality/value

It was possible to identify the most used process modeling languages in smart environments and understand how these languages assist control and manage smart processes. Besides, the authors highlighted challenges, new perspectives and the need for future works in the field.
Exploring an adaptability approach: how creative return processors impact firm performance
Authors: Espinosa Jennifer A. , Stock James , Ortinau David J. , Monahan Lisa
Published: March 2021

Purpose

The authors explore complex adaptive systems (CAS) theory as an updated theoretical perspective for managing product returns that better matches the chaotic nature of recent consumer behaviors. CAS theory highlights the importance of agents who create and self-organize to help systems adapt in unpredictable environments.

Design/methodology/approach

This research utilizes data collected from return managers in an online survey and applies regression analyses to estimate the influence of the focal variables.

Findings

Empirical evidence of the firm flexibility–firm adaptability link is established, and return processor creativity positively relates to this link. The firm flexibility–firm adaptability link fully mediates the relationship between return processor creativity and returns management performance and partially mediates the relationship between return processor creativity and relationship quality. Nonmediated effects were observed for turnover and revenue size.

Practical implications

Managers of returns who embrace an adaptability approach become facilitators of returns by supporting processor creativity. Enhancing the autonomy of processors in their day-to-day work increases the knowledge-creation capabilities of the firm, which helps the firm move forward and adapt in an uncertain environment.

Originality/value

This research presents empirical evidence of the underlying mechanisms of CAS theory in the product returns context by studying processor agents and argues that CAS theory better fits the current dynamics of the product returns environment. Further, this paper extends work by Espinosaet al.(2019) and Nilsson (2019) by studying how a specific human characteristic – creativity – impacts product returns management.