bluuebunny/crossref_metadata_2025 huggingface dataset:
Resonance in the K2-19 system is at odds with its high reported eccentricities
Authors: Petit Antoine C , Petigura Erik A , Davies Melvyn B , Johansen Anders
Published: June 2020

K2-19 hosts a planetary system composed of two outer planets, b and c, with size of 7.0 ± 0.2 R⊕ and 4.1 ± 0.2 R⊕, and an inner planet, d, with a radius of 1.11 ± 0.05 R⊕. A recent analysis of Transit-Timing Variations (TTVs) suggested b and c are close to but not in 3:2 mean motion resonance (MMR) because the classical resonant angles circulate. Such an architecture challenges our understanding of planet formation. Indeed, planet migration through the protoplanetary disc should lead to a capture into the MMR. Here, we show that the planets are in fact, locked into the 3:2 resonance despite circulation of the conventional resonant angles and aligned periapses. However, we show that such an orbital configuration cannot be maintained for more than a few hundred million years due to the tidal dissipation experienced by planet d. The tidal dissipation remains efficient because of a secular forcing of the innermost planet eccentricity by planets b and c. While the observations strongly rule out an orbital solution where the three planets are on close to circular orbits, it remains possible that a fourth planet is affecting the TTVs such that the four planet system is consistent with the tidal constraints.
Scale-invariant dynamics in the Solar system
Authors: Banik Indranil , Kroupa Pavel
Published: June 2020

The covariant scale-invariant dynamics (SID) theory has recently been proposed as a possible explanation for the observed dynamical discrepancies in galaxies. SID implies that these discrepancies – commonly attributed to dark matter – arise instead from a non-standard velocity-dependent force that causes two-body near-Keplerian orbits to expand. We show that the predicted expansion of the Earth–Moon orbit is incompatible with lunar laser ranging data at >200σ. Moreover, SID predicts that the gravitating mass of any object was much smaller in the past. If true, a low-mass red giant star must be significantly older than in standard theory. This would make it much older than the conventional age of the Universe, which, however, is expected to be similarly old in SID. Moreover, it is not completely clear whether SID truly contains new physics beyond general relativity, with several previous works arguing that the extra degree of freedom is purely mathematical. We conclude that the SID model is falsified at high significance by observations across a range of scales, even if it is theoretically well formulated.
Phase I/II study of tirabrutinib, a second-generation Bruton’s tyrosine kinase inhibitor, in relapsed/refractory primary central nervous system lymphoma
Authors: Narita Yoshitaka , Nagane Motoo , Mishima Kazuhiko , Terui Yasuhito , Arakawa Yoshiki , Yonezawa Hajime , Asai Katsunori , Fukuhara Noriko , Sugiyama Kazuhiko , Shinojima Naoki , Kitagawa Junsaku , Aoi Arata , Nishikawa Ryo
Published: June 2020

Background

The safety, tolerability, efficacy, and pharmacokinetics of tirabrutinib, a second-generation, highly selective oral Bruton’s tyrosine kinase inhibitor, were evaluated for relapsed/refractory primary central nervous system lymphoma (PCNSL).

Methods

Patients with relapsed/refractory PCNSL, Karnofsky performance status ≥70, and normal end-organ function received tirabrutinib 320 and 480 mg once daily (q.d.) in phase I to evaluate dose-limiting toxicity (DLT) within 28 days using a 3 + 3 dose escalation design and with 480 mg q.d. under fasted conditions in phase II.

Results

Forty-four patients were enrolled; 20, 7, and 17 received tirabrutinib at 320, 480, and 480 mg under fasted conditions, respectively. No DLTs were observed, and the maximum tolerated dose was not reached at 480 mg. Common grade ≥3 adverse events (AEs) were neutropenia (9.1%), lymphopenia, leukopenia, and erythema multiforme (6.8% each). One patient with 480 mg q.d. had grade 5 AEs (pneumocystis jirovecii pneumonia and interstitial lung disease). Independent review committee assessed overall response rate (ORR) at 64%: 60% with 5 complete responses (CR)/unconfirmed complete responses (CRu) at 320 mg, 100% with 4 CR/CRu at 480 mg, and 53% with 6 CR/CRu at 480 mg under fasted conditions. Median progression-free survival was 2.9 months: 2.1, 11.1, and 5.8 months at 320, 480, and 480 mg under fasted conditions, respectively. Median overall survival was not reached. ORR was similar among patients harboring CARD11, MYD88, and CD79B mutations, and corresponding wild types.

Conclusion

These data indicate favorable efficacy of tirabrutinib in patients with relapsed/refractory PCNSL.

Trial registration

JapicCTI-173646.
Long-term spaceflight and the cardiovascular system
Authors: Vernice Nicholas A , Meydan Cem , Afshinnekoo Ebrahim , Mason Christopher E
Published: June 2020

While early investigations into the physiological effects of spaceflight suggest the body's ability to reversibly adapt, the corresponding effects of long-term spaceflight (>6 months) are much less conclusive. Prolonged exposure to microgravity and radiation yields profound effects on the cardiovascular system, including a massive cephalad fluid translocation and altered arterial pressure, which attenuate blood pressure regulatory mechanisms and increase cardiac output. Also, central venous pressure decreases as a result of the loss of venous compression. The stimulation of baroreceptors by the cephalad shift results in an approximately 10%–15% reduction in plasma volume, with fluid translocating from the vascular lumen to the interstitium. Despite possible increases in cardiac workload, myocyte atrophy and notable, yet unexplained, alterations in hematocrit have been observed. Atrophy is postulated to result from shunting of protein synthesis from the endoplasmic reticulum to the mitochondria via mortalin-mediated action. While data are scarce regarding their causative agents, arrhythmias have been frequently reported, albeit sublethal, during both Russian and American expeditions, with QT interval prolongation observed in long, but not short duration, spaceflight. Exposure of the heart to the proton and heavy ion radiation of deep space has also been shown to result in coronary artery degeneration, aortic stiffness, carotid intima thickening via collagen-mediated action, accelerated atherosclerosis, and induction of a pro-inflammatory state. Upon return, long-term spaceflight frequently results in orthostatic intolerance and altered sympathetic responses, which can prove hazardous should any rapid mobilization or evacuation be required, and indicates that these cardiac risks should be especially monitored for future missions.
Recommendations for Hospital-Based Physical Therapists Managing Patients With COVID-19
Authors: Felten-Barentsz Karin M , van Oorsouw Roel , Klooster Emily , Koenders Niek , Driehuis Femke , Hulzebos Erik H J , van der Schaaf Marike , Hoogeboom Thomas J , van der Wees Philip J
Published: June 2020

Objective

The COVID-19 pandemic is rapidly evolving and has led to increased numbers of hospitalizations worldwide. Hospitalized patients with COVID-19 experience a variety of symptoms, including fever, muscle pain, tiredness, cough, and difficulty breathing. Elderly people and those with underlying health conditions are considered to be more at risk of developing severe symptoms and have a higher risk of physical deconditioning during their hospital stay. Physical therapists have an important role in supporting hospitalized patients with COVID-19 but also need to be aware of challenges when treating these patients. In line with international initiatives, this article aims to provide guidance and detailed recommendations for hospital-based physical therapists managing patients hospitalized with COVID-19 through a national approach in the Netherlands.

Methods

A pragmatic approach was used. A working group conducted a purposive scan of the literature and drafted initial recommendations based on the knowledge of symptoms in patients with COVID-19 and current practice for physical therapist management for patients hospitalized with lung disease and patients admitted to the intensive care unit. An expert group of hospital-based physical therapists in the Netherlands provided feedback on the recommendations, which were finalized when consensus was reached among the members of the working group.

Results

The recommendations include safety recommendations, treatment recommendations, discharge recommendations, and staffing recommendations. Treatment recommendations address 2 phases of hospitalization: when patients are critically ill and admitted to the intensive care unit, and when patients are severely ill and admitted to the COVID ward. Physical therapist management for patients hospitalized with COVID-19 comprises elements of respiratory support and active mobilization. Respiratory support includes breathing control, thoracic expansion exercises, airway clearance techniques, and respiratory muscle strength training. Recommendations toward active mobilization include bed mobility activities, active range-of-motion exercises, active (assisted) limb exercises, activities-of-daily-living training, transfer training, cycle ergometer, pre-gait exercises, and ambulation.
RADIATION DOSES TO THE EYE LENS AND FOREHEAD OF INTERVENTIONAL RADIOLOGISTS: HOW HIGH AND ON WHAT GROUNDS?
Authors: Psarras M , Ploussi A , Carinou E , Brountzos E , Spiliopoulos S C , Palialexis K , Kelekis A , Filippiadis D , Seimenis I , Efstathopoulos E P
Published: June 2020

The aim of the study was to measure and evaluate the radiation dose to the eye lens and forehead of interventional radiologists (IRs). The study included 96 procedures (lower-limb percutaneous transluminal angioplasties, embolisations/chemoembolisations and vertebroplasties) performed by 6 IRs. A set of seven thermoluminescence dosemeters was allocated to each physician. The highest dose per procedure was found for the left eye lens of the primary operator in vertebroplasties (1576 μSv). Left and right eye doses were linearly correlated to left and right forehead doses, respectively. A workload-based estimation of the annual dose to participating IRs revealed that the occupational dose limit for the eye lens can be easily exceeded. The left eye dose of ΙRs must be routinely monitored on a personalised basis. Τhe left eye dose measurement provides a reliable assessment of the ipsilateral forehead dose, along with valid estimations for the right eye and right forehead doses.
Individual Variation in Functional Brain Network Topography is Linked to Schizophrenia Symptomatology
Authors: Nawaz Uzma , Lee Ivy , Beermann Adam , Eack Shaun , Keshavan Matcheri , Brady Roscoe
Published: June 2020

Resting-state fMRI (rsfMRI) demonstrates that the brain is organized into distributed networks. Numerous studies have examined links between psychiatric symptomatology and network functional connectivity. Traditional rsfMRI analyses assume that the spatial organization of networks is invariant between individuals. This dogma has recently been overturned by the demonstration that networks show significant variation between individuals. We tested the hypothesis that previously observed relationships between schizophrenia-negative symptom severity and network connectivity are actually due to individual differences in network spatial organization. Forty-four participants diagnosed with schizophrenia underwent rsfMRI scans and clinical assessments. A multivariate pattern analysis determined how whole-brain functional connectivity correlates with negative symptom severity at the individual voxel level. Brain connectivity to a region of the right dorsolateral prefrontal cortex correlates with negative symptom severity. This finding results from individual differences in the topographic distribution of 2 networks: the default mode network (DMN) and the task-positive network (TPN). Both networks demonstrate strong (r = ~0.49) and significant (P < .001) relationships between topography and symptom severity. For individuals with low symptom severity, this critical region is part of the DMN. In highly symptomatic individuals, this region is part of the TPN. Previously overlooked individual variation in brain organization is tightly linked to differences in schizophrenia symptom severity. Recognizing critical links between network topography and pathological symptomology may identify key circuits that underlie cognitive and behavioral phenotypes. Individual variation in network topography likely guides different responses to clinical interventions that rely on anatomical targeting (eg, transcranial magnetic stimulation [TMS]).
Enhancing Psychosis Risk Prediction Through Computational Cognitive Neuroscience
Authors: Gold James M , Corlett Philip R , Strauss Gregory P , Schiffman Jason , Ellman Lauren M , Walker Elaine F , Powers Albert R , Woods Scott W , Waltz James A , Silverstein Steven M , Mittal Vijay A
Published: June 2020

Research suggests that early identification and intervention with individuals at clinical high risk (CHR) for psychosis may be able to improve the course of illness. The first generation of studies suggested that the identification of CHR through the use of specialized interviews evaluating attenuated psychosis symptoms is a promising strategy for exploring mechanisms associated with illness progression, etiology, and identifying new treatment targets. The next generation of research on psychosis risk must address two major limitations: (1) interview methods have limited specificity, as recent estimates indicate that only 15%–30% of individuals identified as CHR convert to psychosis and (2) the expertise needed to make CHR diagnosis is only accessible in a handful of academic centers. Here, we introduce a new approach to CHR assessment that has the potential to increase accessibility and positive predictive value. Recent advances in clinical and computational cognitive neuroscience have generated new behavioral measures that assay the cognitive mechanisms and neural systems that underlie the positive, negative, and disorganization symptoms that are characteristic of psychotic disorders. We hypothesize that measures tied to symptom generation will lead to enhanced sensitivity and specificity relative to interview methods and the cognitive intermediate phenotype measures that have been studied to date that are typically indicators of trait vulnerability and, therefore, have a high false positive rate for conversion to psychosis. These new behavioral measures have the potential to be implemented on the internet and at minimal expense, thereby increasing accessibility of assessments.
Undocumented, not Unengaged: Local Immigration Laws and the Shaping of Undocumented Mexicans’ Political Engagement
Authors: García Angela S
Published: June 2020

cholars have long demonstrated that laws convey messages to people about how government views them and that these messages impact targeted groups’ political behavior. Drawing from this insight, this study asks if and how local immigration laws shape the political lives of undocumented Mexican immigrants in US cities. The article advances a tripartite theory of political engagement to demonstrate that the design of local immigration measures impacts the political socialization, political efficacy, and political participation of immigrant communities on the ground. This multidimensional model contributes a more holistic account of undocumented immigrants’ political engagement than is available in the existing literature. With a matched case comparison of undocumented life in cities with divergent immigration laws, the article shows that local opportunity structures embedded within receiving locales profoundly influence the nature of political engagement for undocumented residents.
The Saint as Medicator: Medicine and the Miraculous in Fifteenth- and Sixteenth-Century Italy
Authors: Kuuliala Jenni
Published: June 2020

This article discusses the interlinkage of medicine and the miraculous in the healing actions of living saints, based on the canonisation dossiers of St Francesca Romana (1440–53) and St Francesco di Paola (1512–17). These documents include a large number of miracles performed by saints during their lifetime, and in a large proportion of these cases, the holy person administered some kind of medical substance to an infirm devotee before or while performing the miracle. While the commissioners of canonisation inquests had to determine that the cure was of a miraculous origin, it appears that for the devotees the medical and miraculous acts were an inseparable part of the same continuum. Occasional conflicts arose with medical professionals, but the living saints also collaborated with them. The connection of a medicating saint and a miracle-performing saint is thus an essential aspect of the medical pluralism of late medieval and early modern societies.
Standardization and adaptability for dissemination of telephone peer support for high-risk groups: general evaluation and lessons learned
Authors: Evans Megan , Tang Patrick Y , Bhushan Nivedita , Fisher Edwin B , Dreyer Valovcin Dawn , Castellano Cherie
Published: June 2020

Beyond demonstrated effectiveness, research needs to identify how peer support can be implemented in real-world settings. Telephone peer support offers one approach to this. The purpose of this study is to evaluate telephone peer support provided by trained peer staff for high-risk groups, implemented according to key tasks or functions of the Reciprocal Peer Support model (RPS) providing both standardization and adaptability. The methods used in the study include the review of contact data for years 2015–2016 from telephone peer support services of Rutgers Health University Behavioral Health Care, serving veterans, police, mothers of children with special needs, and child protection workers; structured interviews with peer supporters and clients; and audit of case notes. Across 2015–2016, peer supporters made 64,786 contacts with a total of 5,616 callers. Adaptability was apparent in 22% of callers’ relationships lasting ≤1 month and 43% ≥1 year, voicemails valued as communicating presence, 92% of callers receiving support with psychosocial issues, 65% with concrete problems, such as medical or other services, 88% receiving social support, and 88% either resolving an issue (e.g., finding employment) or making documented progress (e.g., getting professional treatment, insurance, or children’s services). With the balance of standardization and adaptability provided by the RPS, telephone peer support can address diverse needs and provide diverse contact patterns, assistance, support, and benefits.
The Comparison of Hemoglobin Values Measured by Blood and Continuous Non-Invasive Monitoring (SpHb) in Newborn Infants
Authors: Kazanasmaz Halil , Demir Mahmut
Published: June 2020

Objective

Hemoglobin (Hb) measurement is one of the most commonly used laboratory tests in medical practice. Unnecessary blood sampling, especially in neonatal intensive care units (NICUs), contributes to iatrogenic anemia. Continuous non-invasive monitoring of total Hb (SpHb) was compared with invasive venous blood samples (tHb) in NICU patients.

Methods

Three hundred and ten patients were identified in NICU. Non-invasive Hb measurement was performed immediately before venous blood sampling and comparison of invasive with non-invasive values was undertaken.

Results

There was a strongly positive correlation between SpHb and tHb (r = 0.965, p < 0.001). Bland–Altman analysis was performed in 95% limits of agreement for Hb values measured by both methods. The mean bias between tHb and SpHb measurements was 0.05 g/dl (−1.85 to 1.96). In Passing–Bablok regression analysis, the CUSUM test p value was found to be 0.98 for Hb levels measured by SpHb and tHb; and the difference between the methods was not significant.

Conclusion

In newborns, SpHb method offers reliable Hb values, which are comparable with the more traditional tHb method. Continuous non-invasive monitoring of total Hb may help prevent unnecessary blood sampling and iatrogenic anemia. Further clinical studies are required for the effectiveness of the method in critically ill patients with circulatory disorders.
The Ambrosia Beetle Sueus niisimai (Scolytinae: Hyorrhynchini) is Associated with the Canker Disease Fungus Diatrypella japonica (Xylariales)
Authors: Li You , Skelton James , Adams Sawyer , Hattori Yukako , Smith Matthew E. , Hulcr Jiri
Published: June 2020

Ambrosia beetles in the subtribe Hyorrhynchini are one example of an entire ambrosia beetle lineage whose fungi have never been studied. Here, we identify one dominant fungus associated with a widespread Asian hyorrhynchine beetle Sueus niisimai. This fungus was consistently isolated from beetle galleries from multiple collections. Phylogenetic analyses of combined ITS rDNA and β-tubulin sequences identified the primary fungal symbiont as Diatrypella japonica Higuchi, Nikaido & Hattori (Diatrypaceae, Xylariales, Sordariomycetes), which was recently described as a pathogen of sycamore (Platanus spp.) in Japan. To assess the invasion potential of this beetle-fungus interaction into the U.S., we have investigated the pathogenicity of two D. japonica strains on four species of healthy landscape trees native to the southeastern United States. Only Shumard oak (Quercus shumardii) responded with lesions significantly greater than the control inoculations, but there was no observable dieback or tree mortality. Although disease symptoms were not as prominent as in previous studies of the same fungus in Japan, routine reisolation from the inoculation point suggests that this species is capable of colonizing healthy sapwood of several tree species. Our study shows that the geographical area of its distribution is broader in Asia and potentially includes many hosts of its polyphagous vector. We conclude that the Sueus-Diatrypella symbiosis has high invasion potential but low damage potential, at least on young trees during the growing season.
Complete Genome Sequence Data of Three Xylella fastidiosa subsp. multiplex Strains Isolated from Olive Trees in California, U.S.A.
Authors: O’Leary Michael L. , Burbank Lindsey P. , Krugner Rodrigo , Stenger Drake C.
Published: June 2020

Xylella fastidiosa is a xylem-limited bacterial plant pathogen that causes disease on numerous hosts. Additionally, X. fastidiosa asymptomatically colonizes a wide range of plant species. X. fastidiosa subsp. multiplex has been detected in olive (Olea europaea) trees grown in California, U.S.A., as well as in Europe. Strains of X. fastidiosa subsp. multiplex isolated from California olive trees are not known to cause disease on olive, although some can induce leaf-scorch symptoms on almond (Prunus dulcis). No genome assemblies currently exist for olive-associated X. fastidiosa subsp. multiplex strains; therefore, a hybrid assembly method was used to generate complete genome sequences for three X. fastidiosa subsp. multiplex strains (Fillmore, LM10, and RH1) isolated from olive trees grown in Ventura and Los Angeles counties of California.
Standing up to stigma in epilepsy
Authors: Rank Wendi Pope
Published: June 2020

This article explores the nature of stigma and discusses how stigma negatively affects both adults and children with epilepsy.
Hepatitis A takes hold in the community
Authors: Heavey Elizabeth
Published: June 2020

In 2016, large outbreaks of hepatitis A virus (HAV) infection began to occur among high-risk individuals, including those with a history of drug use and those experiencing homelessness. This article focusses on HAV infection among high-risk individuals in the community, including those experiencing homelessness.
Maternal Mortality From Coronavirus Disease 2019 (COVID-19) in the United States
Authors: Metz Torri D. , Collier Charlene , Hollier Lisa M.
Published: June 2020

Individual state maternal mortality review committees aim to comprehensively review all maternal deaths to not only evaluate the cause of death, but also to assess preventability and make recommendations for action to prevent future deaths. The maternal mortality review committee process remains critical during the coronavirus disease 2019 (COVID-19) pandemic. Maternal deaths due to COVID-19 have been reported in the United States. Some state maternal mortality review committees may choose to expedite review of these deaths in an effort to quickly provide clinicians with information intended to prevent other deaths during the ongoing pandemic. If states opt to pursue rapid review, entry of data into the Maternal Mortality Review Information Application system for submission to the Centers for Disease Control and Prevention will allow for aggregation nationally without duplication. It will be important to review not only deaths directly attributed to COVID-19, but also those that may be indirectly related to the COVID-19 pandemic, such as those influenced by changes in care practices or delays in seeking care during the pandemic. Therefore, regardless of the timing of the review, maternal deaths that occur during the time of the COVID-19 pandemic must be evaluated within that framework to ensure that all factors contributing to the death are considered to better understand the context of each of these tragic events.
Masquelet Technique for Phalangeal Reconstruction and Osteomyelitis
Authors: Pruzansky Mark E. , Lee Yunsoo , Pruzansky Jason
Published: June 2020

Osteomyelitis of the finger presents a challenging problem. Although there are multiple treatments described in the literature, the infection often results in eventual amputation. The authors present a case of an open fracture of the index finger complicated by nonunion, infection, and osteomyelitis. This was successfully treated by the placement of an antibiotic cement spacer and subsequent reconstruction with iliac crest bone graft, after the 2-stage Masquelet technique, using intravenous and oral antibiotics. They show that this technique, although infrequently described in the hand and fingers, can be a successful option for the treatment of phalangeal osteomyelitis and phalangeal reconstruction.
Reweighting Oranges to Apples: Transported RE-LY Trial Versus Nonexperimental Effect Estimates of Anticoagulation in Atrial Fibrillation
Authors: Webster-Clark Michael , Lund Jennifer L. , Stürmer Til , Poole Charles , Simpson Ross J. , Edwards Jessie K.
Published: June 2020

Background:

Results from trials and nonexperimental studies are often directly compared, with little attention paid to differences between study populations. When target and trial population data are available, accounting for these differences through transporting trial results to target populations of interest provides useful perspective. We aimed to compare two-year risk differences (RDs) for ischemic stroke, mortality, and gastrointestinal bleeding in older adults with atrial fibrillation initiating dabigatran and warfarin when using trial transport methods versus nonexperimental methods.

Methods:

We identified Medicare beneficiaries who initiated warfarin or dabigatran from a 20% nationwide sample. To transport treatment effects observed in the randomized evaluation of long-term anticoagulation trial, we applied inverse odds weights to standardize estimates to two Medicare target populations of interest, initiators of: (1) dabigatran and (2) warfarin. Separately, we conducted a nonexperimental study in the Medicare populations using standardized morbidity ratio weighting to control measured confounding.

Results:

Comparing dabigatran to warfarin, estimated two-year RDs for ischemic stroke were similar with trial transport and nonexperimental methods. However, two-year mortality RDs were closer to the null when using trial transport versus nonexperimental methods for the dabigatran target population (transported RD: −0.57%; nonexperimental RD: −1.9%). Estimated gastrointestinal bleeding RDs from trial transport (dabigatran initiator RD: 1.8%; warfarin initiator RD: 1.9%) appeared more harmful than nonexperimental results (dabigatran initiator RD: 0.14%; warfarin initiator RD: 0.57%).

Conclusions:

Differences in study populations can and should be considered quantitatively to ensure results are relevant to populations of interest, particularly when comparing trial with nonexperimental findings. See video abstract: http://links.lww.com/EDE/B703.
Validation of the Chinese version of the Pelvic Organ Prolapse Symptom Score (POP-SS)
Authors: Ma Yidi , Xu Tao , Zhang Ye , Kang Jia , Ma Congcong , Zhu Lan
Published: June 2020

Objective:

The objective of the present study was to translate the Pelvic Organ Prolapse Symptom Score (POP-SS) into Chinese and validate it in a population of Chinese women.

Methods:

The POP-SS questionnaire was translated into simplified Chinese language following an intercultural adaptation procedure. One hundred forty-six patients who met the inclusion criteria were recruited. Among the enrolled patients, 63 underwent surgery for POP and 50 underwent pessary management. They completed the questionnaires at baseline (T1), 1 to 2 weeks later (T2), and 3 months after intervention (T3). Evaluation for psychometric properties was conducted following with the COnsensus-based Standards for the selection of health Measurement INstruments checklist, including internal consistency, test-retest reliability, measurement error, content validity, criterion validity, construct validity, responsiveness, and interpretability.

Results:

The POP-SS was successfully translated into a Chinese version and achieved good content validity. Internal consistency (Cronbach's alpha = 0.796) was good, and test-retest reliability was excellent (intraclass correlation coefficients = 0.98; P < 0.001). The construct validity was verified by factor analysis and consistent with the theoretical structure of the original questionnaire. The POP-SS score was also significantly correlated with Pelvic Floor Distress Inventory-20 (Spearman's correlation coefficient = 0.89, P < 0.001). The confirmatory factor analysis identified two factors: physical symptoms and evacuation symptoms. The mean changes among the participants in very much better (9.80 ± 5.36) and much better (5.67 ± 2.99) groups were larger than those among the participants in the no change group (0.43 ± 2.07). The effect size responsiveness parameter in the much better group (>0.80) was larger than that in the no change group (<0.20). The values of the minimal important change for surgery and pessary groups were both larger than the smallest detectable change, indicating sufficient responsiveness.

Conclusions:

The Chinese version of POP-SS is a reliable and valid instrument and has good sensitivity to change in the population studied.
Performance of the BIG Score in Predicting Mortality in Normotensive Children With Trauma
Authors: Yoon Tae Jin , Ko Yura , Lee Jisook , Huh Yo , Kim Jung Heon
Published: June 2020

Objectives

Children have a larger reserve for traumatic hemorrhagic shock, requiring a score that uses physiologic variables other than hypotension. Recently, the BIG score comprising admission base deficit, international normalized ratio, and the Glasgow Coma Scale has been reported to predict traumatic mortality. We aimed to validate the performance of the BIG score in mortality prediction of normotensive children with trauma.

Methods

We reviewed 1046 injured children (<18 years) who visited a Korean academic hospital from 2010 to 2018, excluding those with age-adjusted hypotension. In-hospital mortality, the BIG score and its predicted mortality, Revised Trauma Score, and Pediatric Trauma Score were calculated. We compared areas under the curve (AUCs) for in-hospital mortality of the 3 scores and did in-hospital and BIG-predicted mortalities.

Results

Of the 1046 children, 554 were enrolled with a 4.9% in-hospital mortality rate. The median BIG score was higher in the nonsurvivors (6.4 [interquartile range, 4.4–9.2] vs 20.1 [16.5–24.8]; P < 0.001). The AUC of the BIG score was 0.94 (95% confidence interval [CI], 0.92–0.96), which was higher than that of Pediatric Trauma Score (0.87 [95% CI, 0.84–0.90]; P < 0.001). The AUC of the BIG score tended to be higher than that of Revised Trauma Score without statistical significance (0.90 [95% CI, 0.87–0.92]; P = 0.130). We noted a parallel between in-hospital and BIG-predicted mortalities. The hemorrhage-related nonsurvivors showed higher median base deficit and BIG score than did the isolated traumatic brain injury-related ones.

Conclusions

The BIG score can predict mortality with excellent accuracy in normotensive children with trauma.
Outcomes and Factors Associated With Prehospital Treatment of Pediatric Anaphylaxis
Authors: Trainor Jennifer L. , Pittsenbarger Zachary E. , Joshi Deepa , Adler Mark D. , Smith Bridget , Gupta Ruchi S.
Published: June 2020

Objective

Anaphylaxis is a potentially life-threatening reaction requiring prompt treatment with intramuscular epinephrine (EPI). We sought to describe presenting features of pediatric anaphylaxis and compare patient characteristics and outcomes of children treated with prehospital EPI with those untreated.

Methods

We abstracted data from emergency department (ED) records for children meeting the National Institute of Allergy & Infectious Disease criteria for anaphylaxis (2015–2017) in one tertiary care children's hospital. We analyzed associations between patient characteristics and outcomes and receipt of prehospital EPI using descriptive statistics and multivariate logistic regression.

Results

Of 414 children presenting with anaphylaxis, 39.4% received IM EPI and 62.1% received antihistamines before hospital arrival. Children with Medicaid received pre–emergency department EPI less frequently than did children with private insurance (24.5% vs 43.8%, P = 0.001). Factors positively associated with prehospital EPI administration were history of food allergy (odds ratio [OR], 4.4 [95% confidence interval {CI}, 2.4–8.2]) or arrival by emergency medical services (OR, 8.0 [95% CI, 4.2–15.0]). Medicaid insurance was associated with decreased odds of prehospital EPI (OR, 0.33 [95% CI, 0.16–0.66]) and prehospital H1-antihistamine use (OR, 0.30 [95% CI, 0.17–0.56]). Prehospital EPI treatment was also associated with decreased rates of observation (37% vs 63%), inpatient admission (38% vs 62%), and intensive care unit admission (20% vs 80%) compared with no pretreatment (P = 0.03).

Conclusions

Prehospital treatment with EPI remains low, and barriers to optimal treatment are more pronounced in children with public insurance. Prehospital treatment with EPI was associated with decreased morbidity including hospitalization and intensive care unit admission.
Characteristics of Diagnosed Concussions in Children Aged 0 to 4 Years Presenting to a Large Pediatric Healthcare Network
Authors: Podolak Olivia E. , Chaudhary Sofia , Haarbauer-Krupa Juliet , Metzger Kristina B. , Curry Allison E. , Kessler Ronni S. , Pfeiffer Melissa R. , Breiding Matthew J. , Master Christina L. , Arbogast Kristy B.
Published: June 2020

Objective

The aim of the study was to comprehensively describe the natural history of concussion in early childhood between 0 and 4 years.

Methods

Retrospective cohort study of 329 patients aged 0 to 4 years, with anInternational Classification of Diseases,Ninth Revision, concussion diagnosis in the Children's Hospital of Philadelphia healthcare network from October 1, 2013, to September 30, 2015. Clinical data were abstracted from the Children's Hospital of Philadelphia electronic health record, which captured all clinical care visits and injury characteristics.

Results

Nearly 9 (86.6%) of 10 patients sought care in the emergency department or urgent care setting, most commonly on the day of injury (56.2%) and as a result of a fall (64.4%). More than two-thirds (64.4%) of patients or their parent/caregiver reported somatic symptoms (ie, vomiting or headache), whereas close to half (49.2%) reported sleep issues. One of 5 patients identified emotional symptoms (21.9%) or visio-vestibular dysfunction (20.4%). Many patients also experienced symptoms not included in standard assessment tools including personality changes (34.0%) and change in appetite (12.8%).

Conclusions

These results provide insight into the clinical characteristics of concussion in early childhood up to 4 years of age. Because assessment in this group relies heavily on parent/caregiver symptom reporting, rather than patient self-report, these results will aid clinicians with the challenge of diagnosing concussions in this population. These findings highlight the need to develop additional tools to adequately and systematically assess common signs and symptoms of concussion in early childhood that may not be included in standard assessment scales routinely used in older adolescents and adults.
The Role of Helicobacter pylori and Serum Pepsinogen Levels in Metachronous Gastric Cancer After Endoscopic Gastrectomy
Authors: Wang Zhen-Yu , Zhang Jian-Guo
Published: June 2020

Purpose:

The current study aimed to explore the role of Helicobacter pylori (Hp) infection and serum pepsinogen (PG) levels in the occurrence of metachronous gastric cancer after endoscopic gastrectomy.

Materials and Methods:

Totally, 50 patients with metachronous gastric cancer, 50 patients with chronic atrophic gastritis and 50 healthy subjects were collected from October 2015 to October 2018. Patients in the gastric cancer group underwent endoscopic gastrectomy. Serum samples were collected for detection and correlation analysis of serum PG I, PG II, and Hp. In addition, the contents of serum PG and gastrin and postoperative adverse events were statistically analyzed.

Results:

There was a statistically significant difference in serum PG I levels, positive Hp infection rate, the number of mast cells, plasma motilin levels and postoperative adverse events among the 3 groups (P<0.01). There was also a significant difference in PG II levels among the groups (P<0.05). On the basis of the results, the amount of inflammatory cells in the gastric cancer group was significantly higher than that in the gastritis group, and there was a remarkable difference in gastric cancer patients before and after operation. Through data analysis, it was found that the levels of PG I and II were the highest in the healthy control group and the lowest in the gastric cancer group, the number of mast cells was the largest in the gastric cancer group, and the level of motilin was the highest in the healthy control group.

Conclusion:

Hp infection and serum PG levels are associated with metachronous gastric cancer.
Seasonal patterns of
Pseudogymnoascus destructans
germination indicate host–pathogen coevolution
Authors: Fischer Nicola M. , Dool Serena E. , Puechmaille Sebastien J.
Published: June 2020

Emerging infectious diseases rank among the most important threats to human and wildlife health. A comprehensive understanding of the mode of infection and presence of potential reservoirs is critical for the development of effective counter strategies. Fungal pathogens can remain viable in environmental reservoirs for extended periods of time before infecting susceptible individuals. This may be the case for
Pseudogymnoascus destructans
(
Pd
), the causative agent of bat white-nose disease. Owing to its cold-loving nature, this fungal pathogen only grows on bats during hibernation, when their body temperature is reduced. Bats only spend part of their life cycle in hibernation and do not typically show signs of infection in summer, raising the question of whether
Pd
remains viable in hibernacula during this period (roughly six months). If so, this could facilitate the re-infection of bats when they return to the sites the following winter. In a laboratory experiment, we determined the germination rate of
Pd
spores kept under constant conditions on a wall-like substrate, over the course of two years. Results showed that the seasonal pattern in
Pd
germination mirrored the life cycle of the bats, with an increased germination rate at times when hibernating bats would naturally be present and lower germination rates during their absence. We suggest that
Pd
is dependent on the presence of hibernating bats and has therefore coupled its germination rate to host availability. Furthermore, we demonstrate that
Pd
spores survive extended periods of host absence and can remain viable for at least two years. There is, however, a strong decrease in spore viability between the first and second years (98%).
Pd
viability for at least two years on a solid mineral-based substrate establishes the potential for environmental reservoirs in hibernacula walls and has strong implications for the efficacy of certain management strategies (e.g. bat culling).
Molecular insights into the powerful mucus-based adhesion of limpets (
Patella vulgata
L.)
Authors: Kang Victor , Lengerer Birgit , Wattiez Ruddy , Flammang Patrick
Published: June 2020

Limpets (
Patella vulgata
L.) are renowned for their powerful attachments to rocks on wave-swept seashores. Unlike adult barnacles and mussels, limpets do not adhere permanently; instead, they repeatedly transition between long-term adhesion and locomotive adhesion depending on the tide. Recent studies on the adhesive secretions (bio-adhesives) of marine invertebrates have expanded our knowledge on the composition and function of temporary and permanent bio-adhesives. In comparison, our understanding of the limpets' transitory adhesion remains limited. In this study, we demonstrate that suction is not the primary attachment mechanism in
P. vulgata
; rather, they secrete specialized pedal mucus for glue-like adhesion. Through combined transcriptomics and proteomics, we identified 171 protein sequences from the pedal mucus. Several of these proteins contain conserved domains found in temporary bio-adhesives from sea stars, sea urchins, marine flatworms and sea anemones. Many of these proteins share homology with fibrous gel-forming glycoproteins, including fibrillin, hemolectin and SCO-spondin. Moreover, proteins with potential protein- and glycan-degrading domains could have an immune defence role or assist degrading adhesive mucus to facilitate the transition from stationary to locomotive states. We also discovered glycosylation patterns unique to the pedal mucus, indicating that specific sugars may be involved in transitory adhesion. Our findings elucidate the mechanisms underlying
P. vulgata
adhesion and provide opportunities for future studies on bio-adhesives that form strong attachments and resist degradation until necessary for locomotion.
Disruption of TFIIH activities generates a stress gene expression response and reveals possible new targets against cancer
Authors: Uriostegui-Arcos Maritere , Aguayo-Ortiz Rodrigo , Valencia-Morales María del Pilar , Melchy-Pérez Erika , Rosenstein Yvonne , Dominguez Laura , Zurita Mario
Published: June 2020

Disruption of the enzymatic activities of the transcription factor TFIIH by the small molecules Triptolide (TPL) or THZ1 could be used against cancer. Here, we used the MCF10A-ErSrc oncogenesis model to compare the effect of TFIIH inhibitors between transformed cells and their progenitors. We report that tumour cells exhibited highly increased sensitivity to TPL or THZ1 and that the combination of both had a synergic effect. TPL affects the interaction between XPB and p52, causing a reduction in the levels of XPB, p52 and p8, but not other TFIIH subunits. RNA-Seq and RNAPII-ChIP-Seq experiments showed that although the levels of many transcripts were reduced, the levels of a significant number were increased after TPL treatment, with maintained or increased RNAPII promoter occupancy. A significant number of these genes encode for factors that have been related to tumour growth and metastasis, suggesting that transformed cells might rapidly develop resistance to TPL/THZ inhibitors. Some of these genes were also overexpressed in response to THZ1, of which depletion enhances the toxicity of TPL, and are possible new targets against cancer.
Topological Aberrance of Structural Brain Network Provides Quantitative Markers of post-TBI Attention Deficits in Children
Authors: Cao Meng , Luo Yuyang , Wu Ziyan , Mazzola Catherine A. , Goodman Arlene , Catania Lori , Alvarez Tara L. , Halperin Jeffrey M. , Li Xiaobo
Published: June 2020

Traumatic brain injury (TBI)-induced attention deficits are among the most common long-term cognitive consequences in children. Most of the existing studies attenpting to understand the neuropathological underpinnings of cognitive and behavioral impairments in TBI have utilized heterogeneous samples and resulted in inconsistent findings. The current research proposed to investigate topological properties of the structural brain network in children with TBI and their associations with TBI-induced attention problems in a more homogeneous subgroup of children who had severe post-TBI attention deficits (TBI-A).

A total of 31 children with TBI-A and 35 group-matched controls were involved in the study. Diffusion tensor imaging-based probabilistic tractography and graph theoretical techniques were used to construct the structural brain network in each subject. Network topological properties were calculated in both global level and regional (nodal) level. Between-group comparisons among the topological network measures and analyses for searching brain-behavioral associations were all corrected for multiple comparisons using Bonferroni method.

Compare to controls, the TBI-A group showed significantly higher nodal local efficiency and nodal clustering coefficient in left inferior frontal gyrus and right transverse temporal gyrus, while significantly lower nodal clustering coefficient in left supramarginal gyrus as well as lower nodal local efficiency in left parahippocampal gyrus. The temporal lobe topological alterations were significantly associated with the post-TBI inattentive and hyperactive symptoms in the TBI-A group.

The results suggest that TBI-related structural re-modularity in the WM subnetworks associated with temporal lobe may play a critical role in the onset of severe post-TBI attention deficits in children. These findings provide valuable input for understanding the neurobiological substrates of TBI-A, and have the potential to serve as a biomarker guiding the development of more timely and tailored strategies for diagnoses and treatments to the affected individuals.
Distinct Cdk9-phosphatase switches act at the beginning and end of elongation by RNA polymerase II
Authors: Parua Pabitra K. , Kalan Sampada , Benjamin Bradley , Sansó Miriam , Fisher Robert P.
Published: June 2020

Reversible phosphorylation of Pol II and accessory factors helps order the transcription cycle. Here we define two kinase-phosphatase switches that operate at different points in human transcription. Cdk9/cyclin T1 (P-TEFb) catalyzes inhibitory phosphorylation of PP1 and PP4 complexes that localize to 3’ and 5’ ends of genes, respectively, and have overlapping but distinct specificities for Cdk9-dependent phosphorylations of Spt5, a factor instrumental in promoter-proximal pausing and elongation-rate control. PP1 dephosphorylates an Spt5 carboxy-terminal repeat (CTR), but not Spt5-Ser666, a site between KOW motifs 4 and 5, whereas PP4 can target both sites. In vivo, Spt5-CTR phosphorylation decreases as transcription complexes pass the cleavage and polyadenylation signal (CPS) and increases upon PP1 depletion, consistent with a PP1 function in termination first uncovered in yeast. Depletion of PP4-complex subunits increases phosphorylation of both Ser666 and the CTR, and promotes redistribution of promoter-proximally paused Pol II into gene bodies. These results suggest that switches comprising Cdk9 and either PP4 or PP1 govern pause release and the elongation-termination transition, respectively.