bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence and Risk Factors of Worsened Activities of Daily Living Status Three Months after Intensive Care Unit Discharge among Critically Ill Patients: A Prospective Cohort Study
Authors: Miyamoto Kyohei , Shibata Mami , Shima Nozomu , Nakashima Tsuyoshi , Tanaka Rikako , Nakamoto Keita , Imanaka Yuriko , Kato Seiya
Published: April 2022

Background: We aimed to determine risk factors associated with worsened activity of daily living (ADL) status three months after intensive care unit (ICU) discharge. Methods: In this prospective, observational study, we enrolled critically ill adult patients that were emergently admitted to an ICU. We assessed ADL status by Barthel index score prior to ICU admission and three months after ICU discharge. The primary outcome was worsened ADL status, defined as a ≥10 decrease in Barthel index score. Results: We enrolled 102 patients (median age was 72 years old, 55% were male, and 87% received mechanical ventilation during ICU stay), and 42 patients (41%) had worsened ADL status three months after discharge from ICU. Multivariate analysis revealed that older age (>70 years old; adjusted odds ratio (aOR) 3.68; 95% confidence interval (95%CI) 1.33–10.19), high burden of chronic illness (aOR 4.11; 95%CI 1.43–11.81), and longer duration of mechanical ventilation (≥4 days; aOR 2.83; 95%CI 1.04–7.69) were independent risk factors for worsened ADL status at three months. Conclusions: Almost half of the critically ill adult patients in this cohort had worsened ADL status after ICU discharge. Older age, high burden of chronic illness, and longer duration of mechanical ventilation were risk factors for worsened ADL status.
Early Trauma-Focused Counseling for the Prevention of Acute Coronary Syndrome-Induced Posttraumatic Stress: Social and Health Care Resources Matter
Authors: von Känel Roland , Meister-Langraf Rebecca E. , Barth Jürgen , Znoj Hansjörg , Schmid Jean-Paul , Schnyder Ulrich , Princip Mary
Published: April 2022

Background: A one-size-fits-all approach might explain why early psychological interventions are largely ineffective in preventing the development of posttraumatic stress disorder (PTSD) symptoms triggered by acute medical events. We examined the hypothesis that social and health care resources are moderators of an intervention effect. Methods: Within 48 h of hospital admission, 129 patients (mean age 58 years, 83% men) with acute coronary syndrome (ACS) self-rated their social support and were randomized to one single session of trauma-focused counseling (TFC) or stress-focused counseling (SFC) (active control intervention). Clinician-rated PTSD symptoms, use of cardiac rehabilitation (CR) and use of psychotherapy were assessed at 3 and 12 months. Random mixed regression multivariable models were used to analyze associations with PTSD symptoms over time. Results: TFC did not prevent ACS-induced PTSD symptom onset better than SFC; yet, there were significant and independent interactions between “intervention” (TFC or SFC) and social support (p = 0.013) and between “intervention” and duration of CR in weeks (p = 0.034). Patients with greater social support or longer participation in CR had fewer PTSD symptoms in the TFC group compared with the SFC group. The number of psychotherapy sessions did not moderate the intervention effect. Conclusions: Early psychological intervention after ACS with a trauma-focused approach to prevent the development of PTSD symptoms may be beneficial for patients who perceive high social support or participate in CR for several weeks.
New Analytical Approach for the Alignment of Different HE4 Automated Immunometric Systems: An Italian Multicentric Study
Authors: Angeloni Antonio , De Vito Corrado , Farina Antonella , Terracciano Daniela , Cennamo Michele , Passerini Rita , Bottari Fabio , Schirinzi Annalisa , Vettori Roberto , Steffan Agostino , Mais Valerio , Coghe Ferdinando , Della Corte Luigi , Bifulco Giuseppe , Baccolini Valentina , Berardelli Elena , Migliara Giuseppe , Anastasi Emanuela
Published: April 2022

Human epididymal secretory protein 4 (HE4) elevation has been studied as a crucial biomarker for malignant gynecological cancer, such us ovarian cancer (OC). However, there are conflicting reports regarding the optimal HE4 cut-off. Thus, the goal of this study was to develop an analytical approach to harmonize HE4 values obtained with different laboratory resources. To this regard, six highly qualified Italian laboratories, using different analytical platforms (Abbott Alinity I, Fujirebio Lumipulse G1200 and G600, Roche Cobas 601 and Abbott Architett), have joined this project. In the first step of our study, a common reference calibration curve (designed through progressive HE4 dilutions) was tested by all members attending the workshop. This first evaluation underlined the presence of analytical bias in different devices. Next, following bias correction, we started to analyze biomarkers values collected in a common database (1509 patients). A two-sided p-value < 0.05 was considered statistically significant. In post-menopausal women stratified between those with malignant gynecological diseases vs. non-malignant gynecological diseases and healthy women, dichotomous HE4 showed a significantly better accuracy than dichotomous Ca125 (AUC 0.81 vs. 0.74, p = 0.001 for age ≤ 60; AUC 0.78 vs. 0.72, p = 0.024 for age > 60). Still, in post-menopausal status, similar results were confirmed in patients with malignant gynecological diseases vs. patients with benign gynecological diseases, both under and over 60 years (AUC 0.79 vs. 0.73, p = 0.006; AUC 0.76 vs. 0.71, p = 0.036, respectively). Interestingly, in pre-menopausal status women over 40 years, HE4 showed a higher accuracy than Ca125 (AUC 0.73 vs. 0.66, p = 0.027), thus opening new perspective for the clinical management of fertile patients with malignant neoplasms, such as ovarian cancer. In summary, this model hinted at a new approach for identifying the optimal cut-off to align data detected with different HE4 diagnostic tools.
Comment on Iida et al. Development of a New Method for Calculating Intraocular Lens Power after Myopic Laser In Situ Keratomileusis by Combining the Anterior–Posterior Ratio of the Corneal Radius of the Curvature with the Double-K Method. J. Clin. Med. 2022, 11, 522
Authors: Cione Ferdinando , De Bernardo Maddalena , Rosa Nicola
Published: April 2022

We read with great interest the article by Iida et al. [...]
Ocular Complications of Giant Cell Arteritis: An Acute Therapeutic Emergency
Authors: Héron Emmanuel , Sedira Neila , Dahia Ouassila , Jamart Céline
Published: April 2022

The risk of blindness, due to acute ischemic ocular events, is the most feared complication of giant cell arteritis (GCA) since the middle of the 20th century. A decrease of its rate has occurred after the advent of corticoid therapy for this vasculitis, but it seems to have stabilized since then. Early diagnosis and treatment of GCA is key to reducing its ocular morbidity. However, it is not uncommon for ophthalmological manifestations to inaugurate the disease, and the biological inflammatory reaction may be mild, making its diagnosis more challenging. In recent years, vascular imaging has opened up new possibilities for the rapid diagnosis of GCA, and ultrasound has taken a central place in fast-track diagnostic processes. Corticosteroid therapy remains the cornerstone of treatment and must begin immediately in patients with visual symptoms and suspicion of GCA. In that situation, the administration route of corticotherapy, intravenous or oral, is less important than its speed of delivery, any hour of delay worsening the prognosis.
T1ρ for Radiotherapy Treatment Response Monitoring in Rectal Cancer Patients: A Pilot Study
Authors: Kooreman Ernst S. , Tanaka Max , ter Beek Leon C. , Peters Femke P. , Marijnen Corrie A. M. , van der Heide Uulke A. , van Houdt Petra J.
Published: April 2022

Quantitative MRI has the potential to produce imaging biomarkers for the prediction of early response to radiotherapy treatment. In this pilot study, a potential imaging biomarker, the T1ρ relaxation time, is assessed for this purpose. A T1ρ sequence was implemented on a 1.5 T MR-linac system, a system that combines an MRI with a linear accelerator for radiation treatment. An agar phantom with concentrations of 1–4% w/w was constructed for technical validation of the sequence. Phantom images were assessed in terms of short-term repeatability and signal-to-noise ratio. Twelve rectal cancer patients, who were treated with 5 × 5 Gy, were imaged on each treatment fraction. Individual changes in the T1ρ values of the gross tumor volume (GTV) showed an increase for most patients, although a paired t-test comparing values in the GTV from the first to the last treatment fraction showed no statistically significant difference. The phantom measurements showed excellent short-term repeatability (0.5–1.5 ms), and phantom T1ρ values corresponded to the literature values. T1ρ imaging was implemented successfully on the MR-linac, with a repeatability comparable to diagnostic systems, although clinical benefit in terms of treatment response monitoring remains to be demonstrated.
Tobacco Smoking and Second-Hand Smoke Exposure Impact on Tuberculosis in Children
Authors: Altet Neus , Latorre Irene , Jiménez-Fuentes María Ángeles , Soriano-Arandes Antoni , Villar-Hernández Raquel , Milà Celia , Rodríguez-Fernández Pablo , Muriel-Moreno Beatriz , Comella-del-Barrio Patricia , Godoy Pere , Millet Joan-Pau , de Souza-Galvão Maria Luiza , Jiménez-Ruiz Carlos A. , Domínguez Jose ,   on behalf of PII Smoking SEPAR Working Group
Published: April 2022

Little is known about whether second-hand smoke (SHS) exposure affects tuberculosis (TB). Here, we investigate the association of cigarette smoke exposure with active TB and latent TB infection (LTBI) in children, analyzing Interferon-Gamma Release Assays’ (IGRAs) performance and cytokine immune responses. A total of 616 children from contact-tracing studies were included and classified regarding their smoking habits [unexposed, SHS, or smokers]. Risk factors for positive IGRAs, LTBI, and active TB were defined. GM-CSF, IFN-γ, IL-2, IL-5, IL-10, IL-13, IL-22, IL-17, TNF-α, IL-1RA and IP-10 cytokines were detected in a subgroup of patients. Being SHS exposed was associated with a positive IGRA [aOR (95% CI): 8.7 (5.9–12.8)] and was a main factor related with LTBI [aOR (95% CI): 7.57 (4.79–11.94)] and active TB [aOR (95% CI): 3.40 (1.45–7.98)]. Moreover, IGRAs’ sensitivity was reduced in active TB patients exposed to tobacco. IL-22, GM-CSF, IL-5, TNF-α, IP-10, and IL-13 were less secreted in LTBI children exposed to SHS. In conclusion, SHS is associated with LTBI and active TB in children. In addition, false-negative IGRAs obtained on active TB patients exposed to SHS, together with the decrease of specific cytokines released, suggest that tobacco may alter the immune response.
Utility of Real-Time Three-Dimensional Echocardiography for the Assessment of Right Ventricular Morphology and Function in Large Animal Models
Authors: Yuchi Yunosuke , Suzuki Ryohei , Higuchi Riho , Saito Takahiro , Teshima Takahiro , Matsumoto Hirotaka , Koyama Hidekazu
Published: April 2022

Real-time three-dimensional echocardiography (RT3DE) enables a noninvasive assessment of right ventricular (RV) morphology. However, no study has evaluated the relationship between RV function obtained by RT3DE and RV pressure-volume loops. This hypothesis-driven, experimental study aimed to assess the utility of RT3DE in the evaluation of RV morphology and function. Ten anesthetized beagle dogs sequentially underwent dobutamine infusion, acute infusion of lactated Ringer’s solution, and furosemide administration to alter RV contractility and loading conditions. RV pressure-volume loop-derived hemodynamic measurements and echocardiography, including two-dimensional speckle-tracking echocardiography and RT3DE, were performed in each study protocol. Bland–Altman analysis showed strong agreement in RV volume, ejection fraction, and stroke volume obtained by right heart catheterization and RT3DE. Multiple regression analyses revealed that the peak myocardial velocity of the lateral tricuspid annulus (RV s’) and global RV longitudinal strain rate were significantly associated with end-systolic elastance (adjusted r2 = 0.66, p < 0.001). RV s’, RV free wall longitudinal strain, and RT3DE-derived stroke volume/end-systolic RV volume ratio were associated with RV pressure-volume loops-derived end-systolic/arterial elastance ratio (adjusted r2 = 0.34, p < 0.001). RT3DE could detect the changes in catheterization-derived RV volume with a strong agreement and might be useful in estimating RV-pulmonary arterial coupling.
Dual Biologic Therapy for the Treatment of Pediatric Inflammatory Bowel Disease: A Review of the Literature
Authors: Wlazło Magdalena , Kierkuś Jarosław
Published: April 2022

Background: pediatric patients with inflammatory bowel diseases (IBD) who qualify for biological therapy represent a group of severely ill patients. They have never been successful with conventional medication. Biologic medications in monotherapy are frequently used in the disease course, however they result in a 1-year remission, which can be maintained in approximately 40% of IBD patients. Method: the present study aims to summarize the review of literature data on the use of therapy with a combination of two biological and small molecule drugs, anti-TNF (infliximab, adalimumab), vedolizumab and ustekinumab, as well as Janus kinase inhibitors (tofacitinib). The risks associated with the use of dual biological therapy and potential adverse effects are particularly important. The literature data was reviewed using the following terms: “use of combination biologic in paediatric IBD”, “combination biologics”, and “dual biologic for treatment of Inflammatory Bowel Disease”. Conclusion: the use of dual biological therapy is a new therapeutic option. In pediatric IBD, combining the different mechanisms of action of the two biological drugs seems to be safe and effective. Anti-TNF drugs with vedolizumab or ustekinumab may be a particularly beneficial combination. Nevertheless, the clarification and justification of potential advantages of combined biological therapies in further studies, such as randomized control trials, are needed.
What Predicts Improvement of Dizziness after Multimodal and Interdisciplinary Day Care Treatment?
Authors: Prell Tino , Finn Sigrid , Zipprich Hannah M. , Axer Hubertus
Published: April 2022

Background: Vertigo and dizziness are common in community-dwelling people and can be treated in specialized multidisciplinary settings. To develop tailored interventions, however, we have to explore risk factors for favorable and unfavorable outcomes. Methods: We prospectively investigated patients with chronic vertigo and dizziness subjected to our 5-day multimodal and interdisciplinary day care treatment in the Center for Vertigo and Dizziness of Jena University Hospital, Germany. The Vertigo Severity Scale (VSS), the Body Sensations Questionnaire (BSQ), the Hospital Anxiety and Depression Scale (HADS), the Agoraphobic Cognitions Questionnaire (ACQ), the Mobility Inventory (MI), and the burden and intensity of dizziness (using a visual analogue scale) were assessed at baseline (n = 754) and after 6 months (n = 444). In addition, 14 Likert-scaled questions were used to quantify the change in personal attitude and behavior towards the complaints after 6 months. Results: Dizziness-related burden and intensity improved with a large effect size. The largest improvement was seen in the attitudes towards dizziness, the understanding of somatic causes, and the perceived ability to influence dizziness. However, the ability to work and to carry out professional activity was improved to a lesser extent. The overall improvement of dizziness was associated with the absence of a depressive mood, a short duration of vertigo, a lower VSS, a lower perceived intensity of vertigo, and distinct vertigo diagnoses, namely Meniere’s disease, vestibular migraine, vestibular neuritis, vestibular paroxysmia, and vestibular schwannoma. Worsening of dizziness/vertigo was associated with depressive symptoms, permanent vertigo, distinct vertigo diagnoses (central vertigo, multisensory deficit), and a higher perceived burden due to vertigo. Conclusion: The six-month outcome of patients with dizziness presented to a specialized outpatient clinic appears to be favorable. Nevertheless, people with the abovementioned risk factors at baseline have less benefit and probably need adapted and tailored vertigo interventions to improve long-term outcome.
Mechanisms for Overpressure Development in Marine Sediments
Authors: Li Chong , Zhan Linsen , Lu Hailong
Published: April 2022

Overpressure is widely developed in marine sediments; it is not only a critical factor related to hydrocarbon accumulation, but also a serious safety issue for oil/gas exploration and exploitation. Although the mechanisms for overpressure development in sedimentary basins have been intensively studied, some new mechanisms are proposed for overpressure development with the advancements in marine geological investigation, e.g., natural gas hydrate formation and microbial activity. In this study, the mechanisms for overpressure development are reviewed and further classified as being related to associated physical, chemical, and biological processes. The physical overpressure mechanisms include disequilibrium compaction, hydrate formation sealing, degasification, buoyancy, hydrothermal pressuring, tectonic movement, overpressure transfer, etc. The chemical overpressure mechanisms are ascribed to hydrate decomposition, diagenesis, hydrocarbon generation, etc. The biological overpressure mechanisms are mainly induced by microbial gas production and microbial plugging. In gas hydrate-bearing sediments, overpressure is a critical factor affecting the formation and distribution of gas hydrate. The mechanisms for overpressure development in marine gas hydrate systems are associated with permeability deterioration due to hydrate formation and free gas accumulation below bottom-simulating reflectors (BSR). In marine sediments, overpressure developments are generally related to a sediment layer of low permeability above and natural gas accumulation below, and overpressure is mainly developed below a sulphate–methane interface (SMI), because methane will be consumed by anaerobic oxidation above SMI.
Discretization-Strategy-Based Solution for Berth Allocation and Quay Crane Assignment Problem
Authors: Tang Min , Ji Bin , Fang Xiaoping , Yu Samson S.
Published: April 2022

The continuous berth allocation and quay crane assignment problem considers the size of berths and ships, the number of quay cranes, the dynamic ships and non-crossing constraints of quay cranes. In this work, a mixed-integer linear programming model of this problem is established, aiming at minimizing the total stay time and delay penalty of ships. To solve the model, the continuous berth is separated into discrete segments via a proposed discretization strategy. Thereafter, a large neighborhood search algorithm composed of the random removal operator and relaxed sorting-based insertion operator and a backtracking comparison-based constraint repair strategy are proposed. The effectiveness of the model and algorithm presented is verified via real-life instances with different characteristics, and the performances of different combinations of removal operators and insertion operators in the large neighborhood search algorithmic framework are analyzed. Numerical results show that the large neighborhood search algorithm can optimally solve the small-scale instances in a reasonable time. Meanwhile, the results of large-scale instances show that the large neighborhood search algorithm incorporating the discretization strategy is more efficient than other genetic algorithms based on continuous optimization. With the proposed approach, high-quality berth and quay crane allocation results can be obtained efficiently.
The Symbiotic Relationship between the Antarctic Limpet, Nacella concinna, and Epibiont Coralline Algae
Authors: Cho Boongho , Bae Hyeonmi , Kim Taewon
Published: April 2022

The Antarctic limpet, Nacella concinna, is one of the most abundant benthic marine invertebrates found in the intertidal zone of King George Island, Antarctica. The shell of N. concinna is often encrusted with the coralline algae Clathromorphum obtectulum. In this study, to reveal the relationship between the limpet and coralline algae, we examined how the coralline algae affect the physical condition (survival and health) and morphology of the limpet. We cultured the limpets for 22 days and compared mortality, weight, condition factor (CF), fatty acid content, and the structure of the shell surface between limpets both with and without coralline algae in the laboratory. We also measured the environmental factors (i.e., temperature, pH, and salinity) of the seawater at each sampling site and the CF of the limpets and correlated them with coverage of coralline algae. The presence of coralline algae significantly increased the mortality of the limpets by 40% and the shell weight by 1.4-fold but did not affect the CF. Additionally, coralline algae altered the fatty acid profiles related to the limpet’s lipid metabolism (saturated fatty acids (SFA) and some polyunsaturated fatty acids (PUFA)). Specifically, C16:0, C17:0, C18:0, and total SFA increased, whereas C18:2 and C18:3 decreased. However, observations with a scanning electron microscope showed that shell damage in limpets with coralline algae was much less than in limpets without coralline algae, suggesting that coralline algae may provide protection against endolithic algae. The area of coralline algae on the limpet shell was positively correlated with the pH and temperature of the seawater. The results suggest that although coralline algae are generally assumed to be parasitical, the relationship between N. concinna and coralline algae may change to mutualism under certain conditions.
Fusarium and Neocosmospora Species Associated with Rot of Cactaceae and Other Succulent Plants
Authors: Kamali-Sarvestani Sahar , Mostowfizadeh-Ghalamfarsa Reza , Salmaninezhad Fatemeh , Cacciola Santa Olga
Published: April 2022

Infections by Fusarium and Fusarium-like species on cacti and other succulent plants cause the syndrome known as Fusarium dry rot and soft rot. There are only few records of Fusarium species as pathogens of cacti and other succulent plants from Iran. The objective of this study was the identification and characterization of fusarioid species recovered from ornamental succulents in Shiraz County, Iran. Three fusarioid species, including F. oxysporum, F. proliferatum, and Neocosmospora falciformis (formerly F. falciforme), were recovered from 29 diverse species of cacti and other succulents with symptoms of Fusarium dry rot and soft rot. The three fungal species were identified on the basis of morphological characters and the phylogenetic analysis of the translation elongation factor1-α (tef1) nuclear gene. The F. oxysporum isolates were identified as F. oxysporum f. sp. opuntiarum. The pathogenicity of the three fusarioid species was tested on a range of economically important ornamental succulents, mostly in the Cactaceae family. The three species showed a broad host spectrum and induced different types of symptoms on inoculated plants, including soft and dry rot, chlorosis, necrotic spots, wilt, drying, root and crown rot. This is the first report of N. falciformis as a pathogen of succulent plants worldwide.
The Genomic Profile Associated with Risk of Severe Forms of COVID-19 in Amazonian Native American Populations
Authors: Pastana Lucas Favacho , Silva Thays Amâncio , Gellen Laura Patrícia Albarello , Vieira Giovana Miranda , de Assunção Letícia Almeida , Leitão Luciana Pereira Colares , da Silva Natasha Monte , Coelho Rita de Cássia Calderaro , de Alcântara Angélica Leite , Vinagre Lui Wallacy Morikawa Souza , Rodrigues Juliana Carla Gomes , Borges Leal Diana Feio da Veiga , Fernandes Marianne Rodrigues , de Souza Sandro José , Kroll José Eduardo , Ribeiro-dos-Santos André Mauricio , Burbano Rommel Mario Rodríguez , Guerreiro João Farias , de Assumpção Paulo Pimentel , Ribeiro-dos-Santos Ândrea Campos , dos Santos Sidney Emanuel Batista , dos Santos Ney Pereira Carneiro
Published: April 2022

Genetic factors associated with COVID-19 disease outcomes are poorly understood. This study aimed to associate genetic variants in the SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6, XCR1, and ABO genes with the risk of severe forms of COVID-19 in Amazonian Native Americans, and to compare the frequencies with continental populations. The study population was composed of 64 Amerindians from the Amazon region of northern Brazil. The difference in frequencies between the populations was analyzed using Fisher’s exact test, and the results were significant when p ≤ 0.05. We investigated 64 polymorphisms in 7 genes; we studied 47 genetic variants that were new or had impact predictions of high, moderate, or modifier. We identified 15 polymorphisms with moderate impact prediction in 4 genes (ABO, CXCR6, FYCO1, and SLC6A20). Among the variants analyzed, 18 showed significant differences in allele frequency in the NAM population when compared to others. We reported two new genetic variants with modifier impact in the Amazonian population that could be studied to validate the possible associations with COVID-19 outcomes. The genomic profile of Amazonian Native Americans may be associated with protection from severe forms of COVID-19. This work provides genomic data that may help forthcoming studies to improve COVID-19 outcomes.
Outcomes of Conversion Surgery for Metastatic Gastric Cancer Compared with In-Front Surgery Plus Palliative Chemotherapy or In-Front Surgery Alone
Authors: Huang Ruo-Yi , Kou Hao-Wei , Le Puo-Hsien , Kuo Chia-Jung , Chen Tsung-Hsing , Wang Shang-Yu , Chen Jen-Shi , Yeh Ta-Sen , Hsu Jun-Te
Published: April 2022

The survival benefits of conversion surgery in patients with metastatic gastric cancer (mGC) remain unclear. Thus, this study aimed to determine the outcomes of conversion surgery compared to in-front surgery plus palliative chemotherapy (PCT) or in-front surgery alone for mGC. We recruited 182 consecutive patients with mGC who underwent gastrectomy, including conversion surgery, in-front surgery plus PCT, and in-front surgery alone at Linkou Chang Gung Memorial Hospital from 2011 to 2019. The tumor was staged according to the 8th edition of the American Joint Committee on Cancer. Patient demographics and clinicopathological factors were assessed. Overall survival (OS) was evaluated using the Kaplan–Meier curve and compared among groups. Conversion surgery showed a significantly longer median OS than in-front surgery plus PCT or in-front surgery alone (23.4 vs. 13.7 vs. 5.6 months; log rank p < 0.0001). The median OS of patients with downstaging (pathological stage I–III) was longer than that of patients without downstaging (stage IV) (30.9 vs. 18.0 months; p = 0.016). Our study shows that conversion surgery is associated with survival benefits compared to in-front surgery plus PCT or in-front surgery alone in patients with mGC. Patients who underwent conversion surgery with downstaging had a better prognosis than those without downstaging.
Analyzing Precision Medicine Utilization with Real-World Data: A Scoping Review
Authors: Douglas Michael P. , Kumar Anika
Published: April 2022

Precision medicine (PM), specifically genetic-based testing, is currently used in over 140,000 individual tests to inform the clinical management of disease. Though several databases (e.g., the NIH Genetic Testing Registry) demonstrate the availability of these sequencing-based tests, we do not currently understand the extent to which these tests are used. There exists a need to synthesize the body of real-world data (RWD) describing the use of sequencing-based tests to inform their appropriate use. To accomplish this, we performed a scoping review to examine what RWD sources have been used in studies of PM utilization between January 2015 and August 2021 to characterize the use of genome sequencing (GS), exome sequencing (ES), tumor sequencing (TS), next-generation sequencing-based panels (NGS), gene expression profiling (GEP), and pharmacogenomics (PGx) panels. We abstracted variables describing the use of these types of tests and performed a descriptive statistical analysis. We identified 440 articles in our search and included 72 articles in our study. Publications based on registry databases were the most common, followed by studies based on private insurer administrative claims. Slightly more than one-third (38%) used integrated datasets. Two thirds (67%) of the studies focused on the use of tests for oncological clinical applications. We summarize the RWD sources used in peer-reviewed literature on the use of PM. Our findings will help improve future study design by encouraging the use of centralized databases and registries to track the implementation and use of PM.
Incident Rheumatoid Arthritis Following Statin Use: From the View of a National Cohort Study in Korea
Authors: Kwon Mi Jung , Kim Joo-Hee , Kim Ji Hee , Park Hye-Rim , Kim Nan Young , Hong Sangkyoon , Choi Hyo Geun
Published: April 2022

Safety issues regarding the potential risk of statins and incident rheumatoid arthritis (RA) have been raised, but the existing data are largely based on Caucasian populations, and continue to have biases and require further validation in Asian populations. Here, we aimed to verify the risk of RA depending on the duration of previous statin use and statin types using a large-scale, nationwide database. This study enrolled 3149 patients with RA and 12,596 matched non-RA participants from the national health insurance database (2002–2015), and investigated their statin prescription histories for two years before the index date. Propensity score overlap-weighted logistic regression was applied after adjusting for multiple covariates. The prior use of any statins and, specifically, the long-term use of lipophilic statins (>365 days) were related to a lower likelihood of developing RA ((odds ratio (OR) = 0.73; 95% confidence intervals (CI) = 0.63–0.85, p < 0.001) and (OR = 0.71; 95% CI = 0.61–0.84, p < 0.001), respectively). Subgroup analyses supported these preventive effects on RA in those with dyslipidemia, independent of sex, age, smoking, alcohol use, hypertension, and hyperglycemia. Hydrophilic statin use or short-term use showed no such associations. Our study suggests that prior statin use, especially long-term lipophilic statin use, appears to confer preventive benefits against RA.
Defect Coverage after Forequarter Amputation—A Systematic Review Assessing Different Surgical Approaches
Authors: Ehrl Denis , Wachtel Nikolaus , Braig David , Kuhlmann Constanze , Dürr Hans Roland , Schneider Christian P. , Giunta Riccardo E.
Published: April 2022

Autologous fillet flaps are a common reconstructive option for large defects after forequarter amputation (FQA) due to advanced local malignancy or trauma. The inclusion of osseous structures into these has several advantages. This article therefore systematically reviews reconstructive options after FQA, using osteomusculocutaneous fillet flaps, with emphasis on personalized surgical technique and outcome. Additionally, we report on a case with an alternative surgical technique, which included targeted muscle reinnervation (TMR) of the flap. Our literature search was conducted in the PubMed and Cochrane databases. Studies that were identified were thoroughly scrutinized with regard to relevance, resulting in the inclusion of four studies (10 cases). FQA was predominantly a consequence of local malignancy. For vascular supply, the brachial artery was predominantly anastomosed to the subclavian artery and the brachial or cephalic vein to the subclavian or external jugular vein. Furthermore, we report on a case of a large osteosarcoma of the humerus. Extended FQA required the use of the forearm for defect coverage and shoulder contour reconstruction. Moreover, we performed TMR. Follow-up showed a satisfactory result and no phantom limb pain. In case of the need for free flap reconstruction after FQA, this review demonstrates the safety and advantage of osteomusculocutaneous fillet flaps. If the inclusion of the elbow joint into the flap is not possible, we recommend the use of the forearm, as described. Additionally, we advocate for the additional implementation of TMR, as it can be performed quickly and is likely to reduce phantom limb and neuroma pain.
Metagenomic Analysis of Plasma Microbial Extracellular Vesicles in Patients Receiving Mechanical Ventilation: A Pilot Study
Authors: Park Jinkyeong , Lee Jae Jun , Hong Yoonki , Seo Hochan , Shin Tae-Seop , Hong Ji Young
Published: April 2022

Background: Previous studies reported a significant association between pneumonia outcome and the respiratory microbiome. There is increasing interest in the roles of bacterial extracellular vesicles (EVs) in various diseases. We studied the composition and function of microbiota-derived EVs in the plasma of patients receiving mechanical ventilation to evaluate whether they can be used as a diagnostic marker and to predict clinical outcomes. Methods: Plasma samples (n = 111) from 59 mechanically ventilated patients (41 in the pneumonia group; 24 in the nursing home and hospital-associated infection [NHAI] group) were prospectively collected on days one and seven. After isolating the bacterial EVs from plasma samples, nucleic acid was extracted for 16S rRNA gene pyrosequencing. The samples were evaluated to determine the α and β diversity, bacterial composition, and predicted functions. Results: Principal coordinates analysis revealed significantly different clustering of microbial EVs between the pneumonia and non-pneumonia groups. The proportions of Lactobacillus, Cutibacterium, and Sphingomonas were significantly different between the pneumonia and non-pneumonia groups. In addition, the abundances of Lactobacillus and Bifidobacterium were significantly higher in the non-NHAI than the NHAI group. In the analysis of β diversity, the structure of microbial EVs differed significantly different between 28-day survivors and non-survivors (Bray-Curtis distance, p = 0.014). Functional profiling revealed significant differences between the pneumonia and non-pneumonia groups. The longitudinal change in predicted functions of microbial EV genes showed a significant difference between 28-day survivors and non-survivors. Conclusions: Bacterial microbiota–derived EVs in the plasma have potential as diagnostic and prognostic markers for patients receiving mechanical ventilation. Further large prospective studies are needed to determine the clinical utility of plasma microbiota-EVs in intubated patients.
Dopamine DRD2 and DRD3 Polymorphisms Involvement in Nicotine Dependence in Patients with Treatment-Resistant Mental Disorders
Authors: del Casale Antonio , Paolini Marco , Gentile Giovanna , Borro Marina , Zocchi Clarissa , Fiaschè Federica , Padovano Alessio , Zoppi Teodolinda , Modesti Martina Nicole , De Luca Ottavia , Pomes Leda Marina , Brugnoli Roberto , Ferracuti Stefano , Girardi Paolo , Pompili Maurizio , Simmaco Maurizio
Published: April 2022

Patients affected by mental disorders smoke more than the general population. The reasons behind this habit are genetic, environmental, etc. This study aims to investigate the correlations between some polymorphisms and the smoking habits and nicotine dependence in patients with psychiatric disorders. We recruited 88 patients with treatment-resistant mental disorders, including 35 with major depressive disorder, 43 with bipolar spectrum disorder, and 10 with schizophrenia spectrum disorder. We carried out a clinical and psychometric assessment on current smoking habits, years of smoking, number of daily cigarettes, and level of nicotine addiction. The patients performed a peripheral blood sample for DNA analyses of different polymorphisms. We searched for correlations between the measures of nicotine addiction and analysed genotypes. The expression of the T allele of the DRD2 rs1800497 and DRD3 rs6280 polymorphisms significantly correlated with a lower level of nicotine dependence and lower use of cigarettes. We did not find significant correlations between nicotine dependence and OPRM1 rs1799971, COMT rs4680 and rs4633 polymorphisms, CYP2A6 rs1801272 and rs28399433, or 5-HTTLPR genotype. Concluding, DRD2 rs1800497 and DRD3 rs6280 polymorphisms are involved in nicotine dependence and cigarette smoking habits in patients with treatment-resistant mental disorders
Epigenetic Signatures of Smoking in Five Brain Regions
Authors: Zillich Lea , Poisel Eric , Streit Fabian , Frank Josef , Fries Gabriel R. , Foo Jerome C. , Friske Marion M. , Sirignano Lea , Hansson Anita C. , Nöthen Markus M. , Witt Stephanie H. , Walss-Bass Consuelo , Spanagel Rainer , Rietschel Marcella
Published: April 2022

(1) Background: Epigenome-wide association studies (EWAS) in peripheral blood have repeatedly found associations between tobacco smoking and aberrant DNA methylation (DNAm), but little is known about DNAm signatures of smoking in the human brain, which may contribute to the pathophysiology of addictive behavior observed in chronic smokers. (2) Methods: We investigated the similarity of DNAm signatures in matched blood and postmortem brain samples (n = 10). In addition, we performed EWASs in five brain regions belonging to the neurocircuitry of addiction: anterior cingulate cortex (ACC), Brodmann Area 9, caudate nucleus, putamen, and ventral striatum (n = 38–72). (3) Results: cg15925993 within the LOC339975 gene was epigenome-wide significant in the ACC. Of 16 identified differentially methylated regions, two (PRSS50 and LINC00612/A2M-AS1) overlapped between multiple brain regions. Functional enrichment was detected for biological processes related to neuronal development, inflammatory signaling and immune cell migration. Additionally, our results indicate the association of the well-known AHRR CpG site cg05575921 with smoking in the brain. (4) Conclusion: The present study provides further evidence of the strong relationship between aberrant DNAm and smoking.
Household Portfolio Allocations: Evidence on Risk Preferences from the Household, Income, and Labour Dynamics in Australia (HILDA) Survey Using Tobit Models
Authors: Khan Safdar Ullah , Ramella Satyanarayana , Rahman Habib Ur , Hyder Zulfiqar
Published: April 2022

This study investigates intrahousehold risk preferences in household portfolio decision-making. Most household finance data are collected at the household level, and it is challenging to come up with an explanation of risk-taking decisions and have a direction on the within-household bargaining mechanisms. We provide these challenging pieces of evidence by applying a Tobit model on panel data taken from waves 2 to 6 of HILDA surveys. Overall, the results indicate that the risk-taking attitude of partners matters in household portfolio allocations. Risk-averse males and their female counterparts invest less in risky assets. Compared with the no-conflict (identical risk preferences) group, male partners with risk-loving behaviour tend to invest more in risky assets. Further, individual risk preferences are sensitive to fluctuations in equity and housing markets in Australia. Taken together, one of the crucial implications of our findings for future research is that household-bargaining models should, perhaps, give more bargaining power to risk-loving males, offering an additional explanation for the determinants of risk-taking behaviour of households. Understanding the risk-taking attitudes of households is important for future work to understand the fraction of households that end up with a negative net worth in recessions or crisis conditions, such as financial crises, pandemics, and wars.
Opaque or Transparent: Quality Disclosure Strategy for Accommodation-Sharing Platforms
Authors: Fan Xin , Cheng T.C.E. , Li Gang
Published: April 2022

Compared with the conventional hotel providing a standardized service, individual supply on an accommodation-sharing platform makes consumers uncertain about service quality, which is mainly caused by information asymmetry between the consumers and individual hosts. In this paper, we develop a game-theoretic model to study the accommodation-sharing platform’s optimal quality information disclosure and its determining factors with consideration of consumer uncertainty. We find that it is optimal to provide either opaque, i.e., completely uninformative, or transparent, i.e., fully informative, quality information. We also examine the impacts of the incumbent hotel and market heterogeneity on the platform’s quality disclosure. The results show that market heterogeneity and the hotel’s service cost jointly affect the platform’s information disclosure strategy. In general, the sharing platform provides opaque information when market heterogeneity is relatively low but provides transparent information when market heterogeneity is relatively high. However, when market heterogeneity is medium, the hotel’s service cost plays a key role in affecting its pricing strategy, hence the information disclosure strategy of the platform. Specifically, a sufficiently high price of the hotel prompts the platform to disclose transparent information. These findings provide guidance for sharing platforms to design their information disclosure systems.
Spatial and Temporal Changes of Landscape Patterns and Their Effects on Ecosystem Services in the Huaihe River Basin, China
Authors: Wang Haoran , Zhang Mengdi , Wang Chuanying , Wang Kaiyue , Wang Chen , Li Yang , Bai Xiuling , Zhou Yunkai
Published: April 2022

Landscape pattern changes caused by human activities are among the most important driving factors affecting ecosystem spatial structure and components, and significantly impact ecosystem services. Understanding the relationship between landscape patterns and ecosystem services is important for improving regional conservation and establishing ecosystem management strategies. Taking the Huaihe River Basin as an example, this study used land-use data, meteorological data, and topographic data to analyze the spatial and temporal changes in landscape patterns via landscape transfer matrix and landscape indices, and measured four ecosystem services (water retention, soil retention, carbon storage, and biodiversity conservation) with the InVEST models. Furthermore, correlation analysis and global spatial autocorrelation coefficient were used to analyze the impact of landscape pattern changes on ecosystem services. The results showed grassland and farmland areas had continuously decreased, while built-up land and affected water had significantly increased. Landscape fragmentation was reduced, the connectivity between patches was weakened, landscape heterogeneity, evenness, and patch irregularity were increased. Changes in landscape composition and configuration have affected the ecosystem services of the Huaihe River Basin. The reduction in grassland areas and the increase in built-up land areas have significantly reduced the capacity for soil retention, carbon storage, and biodiversity conservation. Spatially, regions with low landscape fragmentation and high patch connectivity had a higher water retention capacity and biodiversity conservation, while soil retention and carbon storage were opposite. Temporally, reduction of landscape fragmentation and increase of patch shape irregularity had a negative effect on water retention, carbon storage, and biodiversity conservation, while soil retention was not sensitive to these changes. The findings in this paper promote an understanding of the relationship between landscape patterns and ecosystem services on a large scale and provide theoretical guidance for ecosystem management and protection planning in the Huaihe River Basin, China.
Why Is Inflectional Morphology Difficult to Borrow?—Distributing and Lexicalizing Plural Allomorphy in Pennsylvania Dutch
Authors: Fisher Rose , Natvig David , Pretorius Erin , Putnam Michael T. , Schuhmann Katharina S.
Published: April 2022

In this article we examine the allomorphic variation found in Pennsylvania Dutch plurality. In spite of over 250 years of variable contact with English, Pennsylvania Dutch plural allomorphy has remained largely distinct from English, except for a number of loan words and borrowings from English. Adopting a One Feature-One Head (OFOH) Architecture that interprets licit syntactic objects as spans, we argue that plurality is distributed across different root-types, resulting in stored lexical-trees (L-spans) in the bilingual mental lexicon. We expand the traditional feature inventory to be ‘mixed,’ consisting of both semantically-grounded features as well as ‘pure’ morphological features. A key claim of our analysis is that the s-exponent in Pennsylvania Dutch shares a syntactic representation for native and English-origin roots, although it is distinct from a ‘monolingual’ English representation. Finally, we highlight how our treatment of plurality in Pennsylvania Dutch, and allomorphic variation more generally, makes predictions about the nature of bilingual morphosyntactic representations.
India and Refugee Law: Gauging India’s Position on Afghan Refugees
Authors: Alexander Atul , Singh Nakul
Published: April 2022

The turbulent transition of power from the Ghani administration to the Taliban regime has not only signalled a death knell to the fundamentals of representative democracy, but it has also provided fertile ground for the large-scale exodus of refugees into neighbouring nations. In view of this, a scrutiny of the Indian state’s response to the influx of Afghan refugees is warranted. India is not a signatory to the 1951 Refugee Convention, nor to the 1967 Protocol, and, in the absence of any concrete national refugee law and policy, Afghans who are seeking refugee status are processed on a haphazard case-by-case basis. In chalking out a future course of action, this paper aims to analyse India’s response to the possible Afghan refugee inflow in the aftermath of the Taliban takeover and in light of India’s recent endorsement of the Global Compact on Refugees (GCR). Against the backdrop of the limited mandate of the UNHCR and the lack of “political will” from the successive governments, we contend that the Supreme and High Courts of India have been instrumental in construing a tentative shield of protection for persons already in the country, which is working out of a judicial form of the endorsement of the non-refoulment principle, in the absence of legislative and executive commitments, and the preferential “acts of kindness” strategy, which discriminates amongst different refugee groups as per origin or religious belief. Moreover, it is argued that the GCR has made few inroads into the overall paradigm as to how refugees are perceived in India. The research concludes that India must enact legislation on refugees for any constructive engagement beyond archaic quick-fix solutions.
2-(5-Acetyl-7-methoxy-2-(4-methoxyphenyl)benzofuran-3-yl)acetic Acid
Authors: Lichitsky Boris V. , Komogortsev Andrey N. , Melekhina Valeriya G.
Published: April 2022

We elaborated a convenient one-step approach for the synthesis of previously unknown 2-(5-acetyl-7-methoxy-2-(4-methoxyphenyl)benzofuran-3-yl)acetic acid. The suggested protocol includes the multicomponent reaction of acetovanillone, 4-methoxyphenylglyoxal and Meldrum’s acid. We have demonstrated that the considered reaction is a one-pot telescoped process including the preliminary condensation of the components in MeCN followed by acid-catalyzed cyclization. The structure of the synthesized product was confirmed by 1H, 13C-NMR spectroscopy and high-resolution mass-spectrometry.