bluuebunny/crossref_metadata_2025_split huggingface dataset:
Minimal Residual Disease Detection using a Plasma-only Circulating Tumor DNA Assay in Patients with Colorectal Cancer
Authors: Parikh Aparna R. , Van Seventer Emily E. , Siravegna Giulia , Hartwig Anna V. , Jaimovich Ariel , He Yupeng , Kanter Katie , Fish Madeleine G. , Fosbenner Kathryn D. , Miao Benchun , Phillips Susannah , Carmichael John H. , Sharma Nihaarika , Jarnagin Joy , Baiev Islam , Shah Yojan S. , Fetter Isobel J. , Shahzade Heather A. , Allen Jill N. , Blaszkowsky Lawrence S. , Clark Jeffrey W. , Dubois Jon S. , Franses Joseph W. , Giantonio Bruce J. , Goyal Lipika , Klempner Samuel J. , Nipp Ryan D. , Roeland Eric J. , Ryan David P. , Weekes Colin D. , Wo Jennifer Y. , Hong Theodore S. , Bordeianou Liliana , Ferrone Cristina R. , Qadan Motaz , Kunitake Hiroko , Berger David , Ricciardi Rocco , Cusack James C. , Raymond Victoria M. , Talasaz AmirAli , Boland Genevieve M. , Corcoran Ryan B. 
Published: April 2021

Abstract

Purpose:
Detection of persistent circulating tumor DNA (ctDNA) after curative-intent surgery can identify patients with minimal residual disease (MRD) who will ultimately recur. Most ctDNA MRD assays require tumor sequencing to identify tumor-derived mutations to facilitate ctDNA detection, requiring tumor and blood. We evaluated a plasma-only ctDNA assay integrating genomic and epigenomic cancer signatures to enable tumor-uninformed MRD detection.

Experimental Design:
A total of 252 prospective serial plasma specimens from 103 patients with colorectal cancer undergoing curative-intent surgery were analyzed and correlated with recurrence.

Results:
Of 103 patients, 84 [stage I (9.5%), II (23.8%), III (47.6%), IV (19%)] had evaluable plasma drawn after completion of definitive therapy, defined as surgery only (n = 39) or completion of adjuvant therapy (n = 45). In “landmark” plasma drawn 1-month (median, 31.5 days) after definitive therapy and &gt;1 year follow-up, 15 patients had detectable ctDNA, and all 15 recurred [positive predictive value (PPV), 100%; HR, 11.28 (P &lt; 0.0001)]. Of 49 patients without detectable ctDNA at the landmark timepoint, 12 (24.5%) recurred. Landmark recurrence sensitivity and specificity were 55.6% and 100%. Incorporating serial longitudinal and surveillance (drawn within 4 months of recurrence) samples, sensitivity improved to 69% and 91%. Integrating epigenomic signatures increased sensitivity by 25%–36% versus genomic alterations alone. Notably, standard serum carcinoembryonic antigen levels did not predict recurrence [HR, 1.84 (P = 0.18); PPV = 53.9%].

Conclusions:
Plasma-only MRD detection demonstrated favorable sensitivity and specificity for recurrence, comparable with tumor-informed approaches. Integrating analysis of epigenomic and genomic alterations enhanced sensitivity. These findings support the potential clinical utility of plasma-only ctDNA MRD detection.
See related commentary by Bent and Kopetz, p. 5449
Janus Kinase 3 Deficiency Promotes Vascular Reendothelialization—Brief Report
Authors: Wang Yung-Chun , Cai Dunpeng , Cui Xiao-Bing , Chuang Ya-Hui , Fay William P. , Chen Shi-You 
Published: April 2021

Objective:
The objective of this study is to determine the role of JAK3 (Janus kinase 3) in reendothelialization after vascular injury.

Methods and Results:
By using mouse carotid artery wire injury and rat balloon injury model, we found that JAK3 regulates reendothelialization and endothelial cell proliferation after vascular injury. JAK3 and phospho-JAK3 levels were increased in neointimal smooth muscle cells in response to vascular injury in mice. JAK3 deficiency dramatically attenuated the injury-induced intimal hyperplasia in carotid arteries of both male and female mice. Importantly, JAK3 deficiency caused an increased rate of reendothelialization following mechanical injury. Likewise, knockdown of JAK3 in medial smooth muscle cells elicited an accelerated reendothelialization with reduced intimal hyperplasia following balloon injury in rat carotid arteries. Interestingly, knockdown of JAK3 restored the expression of smooth muscle cell contractile protein smooth muscle α-actin in injury-induced intimal smooth muscle cells while increased the proliferating endothelial cells in the intima area.

Conclusions:
Our results demonstrate a novel role of JAK3 in the regeneration of endothelium after vascular injury, which may provide a new strategy to enhance reendothelialization while suppressing neointimal formation for effective vascular repair from injury.
The Form and Communicative Impact of Shona Postproverbials
Authors: Mamvura Zvinashe , Nyota Shumirai 
Published: April 2021

Abstract
This article explores the syntax-semantics nexus of Shona postproverbials in the contemporary Zimbabwean society. In terms of syntax, Shona postproverbials are aligned to the following types of sentences found in the Shona language; substantival, verbal, and a combination of both. Like traditional proverbs, there is no postproverbial that takes the form of the ideophonic sentence. The communicative power of postproverbials is an inherent, inbuilt, and internal property stemming from their syntactic and lexical properties. The postproverbial forms, studied in this article, exhibit innovation and ingenuity of the users. The communicative force of the postproverbials arises from the correspondence and cross-correspondence of the structures and grammatical items that constitute them. Congruence and contrast of the lexical items found in the postproverbials also contribute to meanings. The study established that, just like the traditional proverbs, postproverbials are pithy and terse philosophical statements that resonate with a people’s collective experience. In most cases, the postproverbials provide a conduit for people to comment on issues regarded as politically ‘taboo’ and sensitive in a society where the state does not tolerate open criticism.
Of Proverbs and Postproverbial (Re)Constructions
Authors: Egbara Chukwudi Christian 
Published: April 2021

Abstract
This paper evaluates postproverbial (re)constructions of selected Igbo proverbs and the ‘altering alternatives’ regenerated from the original Igbo proverbs. Eighteen randomly selected Igbo proverbs, the proverbial expressions and their postproverbial (re)constructions were subjected to critical analysis. The study revealed that there are noticeable changings in rendering of the selected proverbs. These changings occur largely either due to lack of an in-depth knowledge in the usage of the traditional proverbs, disconnection with the custodians/sources of the Igbo proverbs, urbanisation influence on the Igbo speakers or both. Hence the manufacturing of the ‘altering alternatives’, known as postproverbials. The paper, therefore, urges Igbo language speakers and the would-be users, to draw closer by retracing their step in the choice and usage of Igbo proverbs against the near-overbearing influence of proverbials on the autochthonous, symbolic, semantic, and philosophical essence of Igbo traditional proverbs.
The Democratic Republic of the Congo-China’s Deals on Construction of Roads in Exchange of Mines
Authors: Shirambere Philippe Tunamsifu 
Published: April 2021

After 32 years of dictatorship regime and a decade of various armed conflicts. the newly elected DRC government in 2006 was expected to receive US$4 billion from the traditional Western donors for reconstruction and development to help cement peace. Based on the issue of the lack of trust in the public institutions, the West failed to provide its promised aid following its conditionality. Alternatively, Joseph Kabila approached China to secure his cinq chantiers. Without prior conditionality on good-governance and human rights, China agreed to provide its financial support valued at US$ 9 billion in exchange for mines.
Using historical and comparative methods, findings reveal that the Chinese presence in the DRC goes back to the colonial era of the 19th century. The conditionality for financial support seems inadequate for post-conflict countries in need of reconstruction. Also, the Chinese non-interference policy as an alternative to the western approach needs to be transparent.
Characteristics and Causes of Extreme Snowmelt over the Conterminous United States
Authors: Welty Josh , Zeng Xubin 
Published: April 2021

AbstractSnowmelt is an essential process for the health and sustenance of numerous communities and ecosystems across the globe, though it also presents potential hazards when ablation processes are exceedingly rapid. Using 4-km daily snow water equivalent, temperature, and precipitation data for three decades (1988–2017), here we provide a broad characterization of extreme snowmelt episodes over the conterminous United States in terms of magnitude, timing, and coincident synoptic weather patterns. Larger-magnitude extreme snowmelt events usually coincide with minimal precipitation and elevated temperatures. However, certain regions, particularly mountainous regions and the northeastern United States, exhibit greater likelihood of extreme snowmelt events during pronounced rain-on-snow events. During snowmelt extremes, snowmelt rate often exceeds precipitation in many regions. Meteorological patterns and associated water vapor transport most directly connected to extreme events over different regions are classified via a machine-learning technique. Over the 30-yr study period, there is a weakly increasing trend in the frequency of extremes, though this does not necessarily signify an increase in snowmelt magnitudes.
Photophobia and allodynia in persistent post-traumatic headache are associated with higher disease burden
Authors: Cortez Melissa M , Millsap Leah , Rea Natalie A , Sciarretta Christopher , Brennan KC 
Published: April 2021

Objective To assess photophobia and allodynia in subjects with post-traumatic headache and examine how these sensory hypersensitivities associate with clinical measures of disease burden. Background Post-traumatic headache is the most frequent and disabling long-term consequence of mild traumatic brain injury. There is evidence of sensory dysfunction in acute post-traumatic headache, and it is known from other headache conditions that sensory amplifications correlate with more severe disease. However, systematic studies in post-traumatic headache are surprisingly scarce. Methods We tested light and tactile sensitivity, along with measures of disease burden, in 30 persistent post-traumatic headache subjects and 35 controls. Results In all, 79% of post-traumatic headache subjects exhibited sensory hypersensitivity based on psychophysical assessment. Of those exhibiting hypersensitivity, 54% exhibited both light and tactile sensitivity. Finally, sensory thresholds were correlated across modalities, as well as with headache attack frequency. Conclusions In this study, post-traumatic headache subjects with both light and tactile sensitivity had significantly higher headache frequencies and lower sensitivity thresholds to both modalities, compared to those with single or no sensory hypersensitivity. This pattern suggests that hypersensitivity across multiple modalities may be functionally synergistic, reflect a higher disease burden, and may serve as candidate markers of disease.
Creation of a pioneering interdisciplinary genital dermatology unit for Hispanic men: First 269 patients
Authors: Navarrete Jorge , Hernández Juan Manuel , Cristi Joaquín , Eltit Ignacio , Kutscher Patricia , Guillones Astrid , Oberti Virginia , Arrillaga Annie , Della Santa Rodrigo , Echenagusía Pilar , Sosa Tamara , Fernández Cecilia , Martínez Levín , De Cunto Andrea , Bunker Christopher , Vola Magdalena , Agorio Caroline 
Published: April 2021

The role of circumcision in partially protecting against sexually transmitted infections (STIs) and other dermatoses has been documented. Neonatal circumcision is not routinely practiced in South America. Although it is logical to assume that male genital dermatoses are more prevalent in Hispanic men, they are underrepresented in the existing literature. Objective: To describe the epidemiological characteristics from our male genital dermatology unit in Montevideo (Uruguay), the diagnoses, and correlate them with circumcision status and comorbidities. Methods: A retrospective observational cohort study was conducted. A dermatologist and urologist evaluated all patients using standard questionnaires. In 3 years and 8 months, 269 patients were seen. Median age was 41, prevalence of neonatal circumcision was 0.7%, HIV was 4.2%, STIs were 24.9%, non-STIs were 63.9%, and both (STI + non-STI) were 11.2%. Most frequent entities: eczema/balanoposthitis (27.1%), condyloma (24.9%), and lichen sclerosus (15.6%). Data correlating circumcision and other diagnoses did not reach statistical significance. HIV was positively associated with other STIs ( p < 0.05), and an association with balanoposthitis was seen; however, it did not reach statistical significance ( p < 0.1). Main limitation was small sample size. This is the first study of its kind based on Hispanic patients. Collaboration between specialties proved to be fundamental. Further studies are needed in this demographic to find an association between circumcision, comorbidities, and genital dermatoses.
Respiratory-tract infections among geriatrics: prevalence and factors associated with the treatment outcomes
Authors: Akhtar Ali , Hassali Mohamed Azmi Ahmad , Zainal Hadzliana , Ali Irfhan , Iqbal Muhammad Shahid , Khan Amer Hayat 
Published: April 2021

Background: Geriatric individuals are more susceptible to different infections, especially respiratory-tract infections (RTIs) due to their compromised immune system. Hence, the objectives of the present study were to evaluate the prevalence, medication regimen complexity and factors associated with the treatment outcomes of different RTIs among geriatrics. Methods: A retrospective cross-sectional study (5 years) was conducted at the respiratory department, Hospital Pulau Pinang. Patients aged ⩾65 years with confirmed diagnosis of RTI were included in the study. Results: A total of 474 patients were included, and the most prevalent RTIs were community-acquired pneumonia (65.6%) followed by chronic obstructive pulmonary disease (20.7%), bronchitis (8.2%) and hospital-acquired pneumonia (5.5%). Amoxicillin/clavulanate (69.8%), ampicillin/sulbactam (9.1%) and cefuroxime (6.5%) are the most common antibiotics prescribed to treat RTIs among geriatrics. Smoking, alcohol consumption, polypharmacy and presence of other co-morbidities are statistically significant factors associated with treatment outcomes of RTIs among geriatrics. Conclusion: Prevalence of community-acquired pneumonia (65.6%) among older patients aged 65 years and older higher than other RTIs. Smoking, alcohol use, presence of polypharmacy and other co-morbidities are important factors associated with the treatment outcomes of RTIs. The reviews of this paper are available via the supplemental material section.
The prevalence of orthostatic dysregulation among newly graduated female nurses after employment and its associations with autonomic nervous function, stress, and depressive symptoms
Authors: Kawai Mio , Miyai Nobuyuki , Arita Mikio 
Published: April 2021

Objectives: We aimed to examine the prevalence of orthostatic dysregulation among newly graduated female nurses after employment and its associations with autonomic nervous function, stress, and depressive symptoms. Methods: This follow-up study included 48 newly graduated female nurses (aged 22 ± 3 years) employed in acute care hospitals. The orthostatic dysregulation symptoms were evaluated using a screening checklist. A sit-to-stand test was conducted to assess the autonomic nervous function. Subjective stress and depressive symptoms were determined using a self-administered questionnaire. The data were collected at baseline on the first month and on the seventh month of employment. Statistical differences within groups were analyzed using paired t-test and McNemar’s test. The independent associations of orthostatic dysregulation status with stress and depressive symptoms were analyzed using a multivariate logistic regression model. Results: The percentage of individuals who were diagnosed with orthostatic dysregulation increased from 25.0% at baseline to 35.4% at follow-up. Logistic regression analyses revealed that stress and depressive symptoms were closely associated with orthostatic dysregulation status at follow-up, despite a weak association reported at baseline. The participants were categorized according to their orthostatic dysregulation status: among individuals without orthostatic dysregulation at baseline but with orthostatic dysregulation at follow-up, the increase in autonomic nervous activity, as assessed by the coefficient of variation of the R-R intervals, in response to the postural changes was significantly attenuated at follow-up. Furthermore, this group exhibited a significant increase in stress and depressive symptoms. Conclusions: At 7 months after employment, newly graduated nurses showed a higher prevalence of orthostatic dysregulation in combination with autonomic nervous system modulation, which was accompanied by an increase in stress and depressive symptoms. These observations suggest that the orthostatic dysregulation is associated with poor mental and physical health among newly graduated nurses in the early phase of employment.
Gait speed and adverse outcomes following hospitalised exacerbation of COPD
Authors: Walsh Jessica A. , Barker Ruth E. , Kon Samantha S.C. , Jones Sarah E. , Banya Winston , Nolan Claire M. , Patel Suhani , Polgar Oliver , Haselden Brigitte M. , Polkey Michael I. , Cullinan Paul , Man William D-C. 
Published: April 2021

BackgroundThe 4-m gait speed (4MGS) test is a simple physical performance measure and surrogate marker of frailty that is associated with adverse outcomes in older adults. We aimed to assess the ability of 4MGS to predict prognosis in patients hospitalised with acute exacerbations of chronic obstructive pulmonary disease (AECOPD).Methods213 participants hospitalised with AECOPD (52% male, mean age 72 years and mean forced expiratory volume in 1 s (FEV1) 35% predicted) were enrolled. 4MGS and baseline demographics were recorded at hospital discharge. All-cause readmission and mortality were collected for 1 year after discharge and multivariable Cox proportional hazards regressions were performed. Kaplan–Meier and competing risks analyses were conducted comparing time to all-cause readmission and mortality between 4MGS quartiles.Results111 participants (52%) were readmitted and 35 (16%) died during the follow-up period. 4MGS was associated with all-cause readmission, with an adjusted subdistribution hazard ratio of 0.868 (95% CI 0.797–0.945; p=0.001) per 0.1 m·s−1increase in gait speed, and with all-cause mortality, with an adjusted subdistribution hazard ratio of 0.747 (95% CI 0.622–0.898; p=0.002) per 0.1 m·s−1increase in gait speed. Readmission and mortality models incorporating 4MGS had higher discrimination than age or FEV1% pred alone, with areas under the receiver operator characteristic curves of 0.73 and 0.80, respectively. Kaplan–Meier and competing risks curves demonstrated that those in slower gait speed quartiles had reduced time to readmission and mortality (log-rank, both p<0.001).Conclusions4MGS provides a simple means of identifying at-risk patients with COPD at hospital discharge. This provides valuable information to plan post-discharge care and support.
Incidence and predictors of asthma exacerbations in middle-aged and older adults: the Rotterdam Study
Authors: de Roos Emmely W. , Lahousse Lies , Verhamme Katia M.C. , Braunstahl Gert-Jan , in ‘t Veen Johannes C.C.M. , Stricker Bruno H. , Brusselle Guy G.O. 
Published: April 2021

AimThe aim of this study was to investigate occurrence and determinants of asthma exacerbations in an ageing general population.MethodsSubjects aged 45 years or above with physician-diagnosed asthma in the Rotterdam Study, a population-based prospective cohort from January 1991 to May 2018, were assessed for asthma exacerbations. Exacerbations were defined as acute episodes of worsening asthma treated with oral corticosteroids. Cox proportional hazards analysis was used to investigate risk factors for a future exacerbation.ResultsOut of 763 participants with asthma (mean age 61.3 years, 69.2% female), 427 (56.0%) experienced at least one exacerbation, in a mean follow-up time of 13.9 years. The mean annual exacerbation rate was 0.22. Most exacerbations occurred during winter months. Risk factors for exacerbations were a history of previous exacerbations (HR 4.25; 95% CI 3.07–5.90, p<0.001)), respiratory complaints (HR 2.18; 95% CI 1.48–3.21, p<0.001), airflow obstruction (HR 1.52; 95% CI 1.07–2.15, p=0.019), obesity (HR 1.38; 95% CI 1.01–1.87, p=0.040) and depressive symptoms (HR 1.55; 95% CI 1.05–2.29, p=0.027). Compared to those not using respiratory medication, we observed higher hazard ratios for those on short-acting β2-agonists (SABA,i.e.rescue medication) only (HR 3.08, 95% CI 1.61–5.90, p=0.001) than those on controller medication (HR 2.50, 95% CI 1.59–3.92, p<0.001).ConclusionMany older adults with asthma suffer from at least one severe exacerbation. Previous exacerbations, use of SABA without concomitant controller medication, respiratory complaints, obesity, airway obstruction and depression are independent risk factors for exacerbations.
Descriptive analysis of long COVID sequelae identified in a multidisciplinary clinic serving hospitalised and non-hospitalised patients
Authors: Johnsen Stine , Sattler Stefan M. , Miskowiak Kamilla Woznica , Kunalan Keerthana , Victor Alan , Pedersen Lars , Andreassen Helle Frost , Jørgensen Barbara Jolanta , Heebøll Hanne , Andersen Michael Brun , Marner Lisbeth , Hædersdal Carsten , Hansen Henrik , Ditlev Sisse Bolm , Porsbjerg Celeste , Lapperre Thérèse S. 
Published: April 2021

BackgroundThere are emerging data of long-term effects of coronavirus disease 2019 (COVID-19) comprising a diversity of symptoms. The aim of this study was to systematically describe and measure pulmonary and extra-pulmonary post-COVID-19 complications in relation to acute COVID-19 severity.MethodsPatients attending a standard of care 3 months post-hospitalisation follow-up visit and those referred by their general practitioner because of persistent post-COVID-19 symptoms were included. Patients underwent symptomatic, quality of life, pulmonary (lung function and high-resolution computed tomography (HRCT)), cardiac (high-resolution ECG), physical (1-min sit and stand test (1-MSTST), handgrip strength, cardiopulmonary exercise testing (CPET)) and cognitive evaluations.ResultsAll 34 hospitalised and 22 out of 23 non-hospitalised patients had ≥1 complaint or abnormal finding at follow-up. Overall, 67% of patients were symptomatic (Medical Research Council (MRC) ≥2 or COPD assessment test (CAT) ≥10), with no difference between hospitalisedversusnon-hospitalised patients. Pulmonary function (forced expiratory volume in 1 s (FEV1) or diffusing capacity of the lung for carbon monoxide (DLCO)) <80% of predicted) was impaired in 68% of patients.DLCOwas significantly lower in those hospitalised compared to non-hospitalised (70.1±18.0versus80.2±11.2% predicted, p=0.02). Overall, 53% had an abnormal HRCT (predominantly ground-glass opacities) with higher composite computed tomography (CT) scores in hospitalisedversusnon-hospitalised patients (2.3 (0.1–4.8) and 0.0 (0.0–0.3), p<0.001). 1-MSTST was below the 25th percentile in almost half of patients, but no signs of cardiac dysfunction were found. Cognitive impairments were present in 59–66% of hospitalised and 31–44% of non-hospitalised patients (p=0.08).ConclusionThree months after COVID-19 infection, patients were still symptomatic and demonstrated objective respiratory, functional, radiological and cognitive abnormalities, which were more prominent in hospitalised patients. Our study underlines the importance of multidimensional management strategies in these patients.