bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atypical respiratory distress in eastern Democratic Republic of the Congo prior to the COVID-19 pandemic. A case report
Authors: Mateso Guy-Quesney , Baguma Marius , Mwene-Batu Pacifique , Balemba Ghislain Maheshe , Nzabara Fabrice , Makali Samuel , Bedha Aline , Furaha Bonheur , Minani Jimmy , Muhindo Christian Tshongo , Malembaka Espoir Bwenge , Masimango Mannix Imani , Shindano Tony Akilimali , Cikomola Justin Cirhuza , Mubagwa Kanigula 
Published: April 2021

Abstract
Background
Predictions have been made that Africa would be the most vulnerable continent to the novel Coronavirus disease 2019 (COVID-19). Interestingly, the spread of the disease in Africa seems to have been delayed and initially slower than in many parts of the world. Here we report on two cases of respiratory distress in our region before the official declaration of the disease in December 2019, cases which in the present times would be suspect of COVID-19.

Case presentation
These two cases (one 55-year-old man and one 25-year-old woman) of acute respiratory distress secondary to atypical pneumonia were seen in Bukavu, in Eastern Democratic Republic of the Congo (DRC), between September and December 2019. One patient had returned from China and the other had close contacts with travellers from China in the 2 weeks prior to the onset of symptoms. In either case, the aetiology could not be accurately determined. However, the two cases presented a clinical picture (progressive dyspnoea, preceded by dry cough and fever) and laboratory changes (procalcitonin within the normal range, slight inflammation, and lymphopenia) compatible with a viral infection. The chest X-ray series of the first patient showed lesions (reticulations, ground glass, and nodules ≤6 mm) similar to those currently found in COVID-19 patients. In addition, unlike the 25-year-old female patient who had no comorbidity, the 55-year-old male patient who had hypertension as comorbidity, developed a more severe acute respiratory distress which progressed to death.

Conclusion
These cases bring to the attention the fact that COVID-19-like syndromes may have already been present in the region months before the official beginning of the pandemic. This also brings to question whether a prior presence of the disease or infections with related virus may account for the delayed and less extensive development of the pandemic in the region.
Human nasal septal chondrocytes (NSCs) preconditioned on NSC-derived matrix improve their chondrogenic potential
Authors: Noh Yong Kwan , Kim Sung Won , Kim Ik-Hwan , Park Kwideok 
Published: April 2021

Abstract

Background
Extracellular matrix (ECM) has a profound effect on cell behaviors. In this study, we prepare a decellularized human nasal septal chondrocyte (NSC)-derived ECM (CHDM), as a natural (N-CHDM) or soluble form (S-CHDM), and investigate their impact on NSCs differentiation.

Methods
N-CHDM, S-CHDM were obtained from NSC. To evaluate function of NSC cultured on each substrate, gene expression using chondrogenic marker, and chondrogenic protein expression were tested. Preconditioned NSCs-loaded scaffolds were transplanted in nude mice for 3 weeks and analyzed.

Results

When cultivated on each substrate, NSCs exhibited similar cell spread area but showed distinct morphology on N-CHDM with significantly lower cell circularity. They were highly proliferative on N-CHDM than S-CHDM and tissue culture plastic (TCP), and showed more improved cell differentiation, as assessed via chondrogenic marker (Col2, Sox9, and Aggrecan) expression and immunofluorescence of COL II. We also investigated the effect of NSCs preconditioning on three different 2D substrates while NSCs were isolated from those substrates, subsequently transferred to 3D mesh scaffold, then cultivated them
in vitro
or transplanted
in vivo
. The number of cells in the scaffolds was similar to each other at 5 days but cell differentiation was notably better with NSCs preconditioned on N-CHDM, as assessed via real-time q-PCR, Western blot, and immunofluorescence. Moreover, when those NSCs-loaded polymer scaffolds were transplanted subcutaneously in nude mice for 3 weeks and analyzed, the NSCs preconditioned on the N-CHDM showed significantly advanced cell retention in the scaffold, more cells with a chondrocyte lacunae structure, and larger production of cartilage ECM (COL II, glycosaminoglycan).

Conclusions
Taken together, a natural form of decellularized ECM, N-CHDM would present an advanced chondrogenic potential over a reformulated ECM (S-CHDM) or TCP substrate, suggesting that N-CHDM may hold more diverse signaling cues, not just limited to ECM component.
Transient dynamical-thermal-optical system modeling and simulation
Authors: Hahn Luzia , Eberhard Peter 
Published: April 2021

AbstractIn modern high resolution optical systems like astronomical telescopes or lithographic objectives, performance degradations can be caused by various disturbances. Holistic optical system simulation is required to predict the performance or the high precision systems. In this paper a method for transient dynamical-thermal-optical system modeling and simulation is introduced. Thereby, elastic deformation, rigid body motion, and mechanical stresses due to dynamical excitation are calculated using elastic multibody system simulation and temperature changes are determined using thermal finite element analysis. The deformation, the motion, and the mechanically and thermally induced stress index changes are then considered in a gradient-index ray tracing. Finally, the presented method is applied in a dynamical-thermal single lens system.
Karyomegalic interstitial nephritis: diagnosed only when suspected
Authors: Sivakumar Monica , Gaspar Balan Louis , Narasimhan Balakrishnan 
Published: April 2021

Abstract
Background
Karyomegalic interstitial nephritis (KIN) is an uncommon cause of chronic interstitial nephritis that eventually progresses to end-stage renal disease. Overall less than 50 cases have been reported in the literature.

Case presentation
We describe an asymptomatic 25-year-old gentleman with a family history of chronic interstitial nephritis who came to check the status of his kidney functions. On evaluation, he was found to have chronic interstitial nephritis which could not be attributed to a specific etiology. Renal biopsy confirmed the diagnosis of KIN.

Conclusion
KIN remains underdiagnosed. It is important to recognize this entity because of the familial nature, a wide range of differential diagnoses, and prognostic implications. A high index of clinical suspicion is necessary to perform renal biopsy which remains the gold standard for the diagnosis of KIN.
Assessing the risks of SARS-CoV-2 in wildlife
Authors: Delahay R. J. , de la Fuente J. , Smith G. C. , Sharun K. , Snary E. L. , Flores Girón L. , Nziza J. , Fooks A. R. , Brookes S. M. , Lean F. Z. X. , Breed A. C. , Gortazar C. 
Published: April 2021

AbstractThe novel coronavirus SARS-CoV-2 likely emerged from a wildlife source with transmission to humans followed by rapid geographic spread throughout the globe and severe impacts on both human health and the global economy. Since the onset of the pandemic, there have been many instances of human-to-animal transmission involving companion, farmed and zoo animals, and limited evidence for spread into free-living wildlife. The establishment of reservoirs of infection in wild animals would create significant challenges to infection control in humans and could pose a threat to the welfare and conservation status of wildlife. We discuss the potential for exposure, onward transmission and persistence of SARS-CoV-2 in an initial selection of wild mammals (bats, canids, felids, mustelids, great apes, rodents and cervids). Dynamic risk assessment and targeted surveillance are important tools for the early detection of infection in wildlife, and here we describe a framework for collating and synthesising emerging information to inform targeted surveillance for SARS-CoV-2 in wildlife. Surveillance efforts should be integrated with information from public and veterinary health initiatives to provide insights into the potential role of wild mammals in the epidemiology of SARS-CoV-2.
Planning considerations of green corridors for the improvement of biodiversity resilience in suburban areas
Authors: Wang Yuhong , Jia Siqi , Wang Zhe , Chen Yang , Mo Shicong , Sze N. N. 
Published: April 2021

AbstractThe world is experiencing a rapid loss in the biodiversity of pollinator insects. Habitat segmentation caused by infrastructures is one of the contributing factors. To improve the habitat connectivity of pollinator insects, it is proposed in this study to build green corridors for pollinators over linear infrastructures such as highways. In the context of suburban areas of a large city, this study examines differences in air parameters between natural environments and a roadside environment based on monitored and estimated data. Influences of different green corridor designs on floral scent dispersion are also investigated using computational fluid dynamics (CFD) modeling and simulation. It is found that, if flower plants are installed on highway overpasses, the floral scents would be better preserved as compared with those in a natural environment due to the lower concentrations of oxidative radicals in the air above highways. The stronger floral scents and their wider dispersion may help attract pollinators. Conversely, highway air contains a variety of volatine organic compounds (VOCs) that are traced to highway operations and pavements. Hence, the overall profile of VOCs in a highway environment differs from that in a natural environment. Results from CFD modeling and simulation suggest that the use of green corridors planted with flowers on the highway overpass can greatly improve the connectivity of floral scents. Hence, with proper engineering design and right combination of plant species, green corridors built on highway overpasses have the potential to facilitate pollinators to cross the road, thereby improving their habitat connectivity and resilience against declining biodiversity.
Treatment of Pediatric Adrenocortical Carcinoma With Surgery, Retroperitoneal Lymph Node Dissection, and Chemotherapy: The Children's Oncology Group ARAR0332 Protocol
Authors: Rodriguez-Galindo Carlos , Krailo Mark D. , Pinto Emilia M. , Pashankar Farzana , Weldon Christopher B. , Huang Li , Caran Eliana M. , Hicks John , McCarville M. Beth , Malkin David , Wasserman Jonathan D. , de Oliveira Filho Antonio G. , LaQuaglia Michael P. , Ward Deborah A. , Zambetti Gerard , Mastellaro Maria J. , Pappo Alberto S. , Ribeiro Raul C. 
Published: April 2021

PURPOSE Adrenocortical carcinoma (ACC) is a rare aggressive pediatric malignancy with distinct biology. Its treatment follows the principles developed for adults; pediatric-specific studies are scarce. PATIENTS AND METHODS Prospective single-arm risk-stratified interventional study. Study objectives were (1) to describe the outcome of patients with stage I ACC treated with adrenalectomy alone; (2) to describe the outcome of stage II patients (completely resected > 200 cc or > 100 g) treated with adrenalectomy and retroperitoneal lymph node dissection; and (3) to describe the outcome of patients with stage III or IV treated with mitotane and chemotherapy. RESULTS Between September 2006 and May 2013, 78 patients (77 eligible, 51 females) were enrolled. The 5-year event-free survival estimates for stages I (24 patients), II (15 patients), III (24 patients), and IV (14 patients) were 86.2%, 53.3%, 81%, and 7.1%, respectively. The corresponding 5-year overall survival estimates were 95.2%, 78.8%, 94.7%, and 15.6%, respectively. On univariate analysis, age, stage, presence of virilization, Cushing syndrome, or hypertension, germline TP53 status, and presence of a somatic ATRX mutation were associated with outcome. On multivariable analysis, only stage and age were significantly associated with outcome. The probabilities of mitotane and chemotherapy feasibility events were 10.5% and 31.6%, respectively. CONCLUSION Outcome for children with stage I ACC is excellent with surgery. Outcome for patients with stage II disease is inferior despite retroperitoneal lymph node dissection. Patients with stage III ACC have an excellent outcome combining surgery and chemotherapy. Patients with stage IV ACC are older and have a poor outcome; new treatments should be explored for this high-risk group. The combination of mitotane and chemotherapy as prescribed in ARAR0332 resulted in significant toxicity; one third of patients with advanced disease could not complete the scheduled treatment.
Long-Term Outcomes in a Multicenter, Prospective Cohort Evaluating the Prognostic 31-Gene Expression Profile for Cutaneous Melanoma
Authors: Hsueh Eddy C. , DeBloom James R. , Lee Jonathan H. , Sussman Jeffrey J. , Covington Kyle R. , Caruso Hillary G. , Quick Ann P. , Cook Robert W. , Slingluff Craig L. , McMasters Kelly M. 
Published: April 2021

PURPOSE Current guidelines for postoperative management of patients with stage I-IIA cutaneous melanoma (CM) do not recommend routine cross-sectional imaging, yet many of these patients develop metastases. Methods that complement American Joint Committee on Cancer (AJCC) staging are needed to improve identification and treatment of these patients. A 31-gene expression profile (31-GEP) test predicts metastatic risk as low (class 1) or high (class 2). Prospective analysis of CM outcomes was performed to test the hypotheses that the 31-GEP provides prognostic value for patients with stage I-III CM, and that patients with stage I-IIA melanoma and class 2 31-GEP results have metastatic risk similar to patients for whom surveillance is recommended. MATERIALS AND METHODS Two multicenter registry studies, INTEGRATE (ClinicalTrials.gov identifier: NCT02355574 ) and EXPAND (ClinicalTrials.gov identifier: NCT02355587 ), were initiated under institutional review board approval, and 323 patients with stage I-III CM and median follow-up time of 3.2 years met inclusion criteria. Primary end points were 3-year recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS). RESULTS The 31-GEP was significant for RFS, DMFS, and OS in a univariate analysis and was a significant, independent predictor of RFS, DMFS, and OS in a multivariable analysis. GEP class 2 results were significantly associated with lower 3-year RFS, DMFS, and OS in all patients and those with stage I-IIA disease. Patients with stage I-IIA CM and a class 2 result had recurrence, distant metastasis, and death rates similar to patients with stage IIB-III CM. Combining 31-GEP results and AJCC staging enhanced sensitivity over each approach alone. CONCLUSION These data provide a rationale for using the 31-GEP along with AJCC staging, and suggest that patients with stage I-IIA CM and a class 2 31-GEP signature may be candidates for more intense follow-up.
Comprehensive Clinical and Molecular Characterization of KRASG12C-Mutant Colorectal Cancer
Authors: Henry Jason T. , Coker Oluwadara , Chowdhury Saikat , Shen John Paul , Morris Van K. , Dasari Arvind , Raghav Kanwal , Nusrat Maliha , Kee Bryan , Parseghian Christine , Pant Shubham , Jeyakumar Nikeshan , Zhu Limin , Nishioka Yujiro , Fogelman David , Wolff Robert A. , Hong David , Overman Michael J. , Vauthey JeanNicolas , Kopetz Scott , Johnson Benny 
Published: April 2021

PURPOSE KRAS p.G12C mutations occur in approximately 3% of metastatic colorectal cancers (mCRC). Recently, two allosteric inhibitors of KRAS p.G12C have demonstrated activity in early phase clinical trials. There are no robust studies examining the behavior of this newly targetable population. METHODS We queried the MD Anderson Cancer Center data set for patients with colorectal cancer who harbored KRAS p.G12C mutations between January 2003 and September 2019. Patients were analyzed for clinical characteristics, overall survival (OS), and progression-free survival (PFS) and compared against KRAS nonG12C. Next, we analyzed several internal and external data sets to assess immune signatures, gene expression profiles, hypermethylation, co-occurring mutations, and proteomics. RESULTS Among the 4,632 patients with comprehensive molecular profiling, 134 (2.9%) were found to have KRAS p.G12C mutations. An additional 53 patients with single gene sequencing were included in clinical data but excluded from prevalence analysis allowing for 187 total patients. Sixty-five patients had de novo metastatic disease and received a median of two lines of chemotherapy without surgical intervention. For the first three lines of chemotherapy, the median PFS was 6.4 months (n = 65; 95% CI, 5.0 to 7.4 months), 3.9 months (n = 47; 95% CI, 2.9 to 5.9 months), and 3.0 months (n = 21; 95% CI, 2.0 to 3.4 months), respectively. KRAS p.G12C demonstrated higher rates of basal EGFR activation compared with KRAS nonG12C. When compared with an internal cohort of KRAS nonG12C, KRAS p.G12C patients had worse OS. CONCLUSION PFS is poor for patients with KRAS p.G12C metastatic colorectal cancer. OS was worse in KRAS p.G12C compared with KRAS nonG12C patients. Our data highlight the innate resistance to chemotherapy for KRAS p.G12C patients and serve as a historical comparator for future clinical trials.
High-Throughput Drug Screening and Multi-Omic Analysis to Guide Individualized Treatment for Multiple Myeloma
Authors: Coffey David G. , Cowan Andrew J. , DeGraaff Bret , Martins Timothy J. , Curley Niall , Green Damian J. , Libby Edward N. , Silbermann Rebecca , Chien Sylvia , Dai Jin , Morales Alicia , Gooley Ted A. , Warren Edus H. , Becker Pamela S. 
Published: April 2021

PURPOSE Multiple myeloma (MM) is a genetically heterogeneous malignancy characterized by variable treatment responses. Although numerous drugs have been approved in recent years, the ability to predict treatment response and tailor individual therapy is limited by the absence of robust predictive biomarkers. The goal of this clinical trial was to use ex vivo, high-throughput screening (HTS) of 170 compounds to predict response among patients with relapsed or refractory MM and inform the next treatment decisions. Additionally, we integrated HTS with multi-omic analysis to uncover novel associations between in vitro drug sensitivity and gene expression and mutation profiles. MATERIALS AND METHODS Twenty-five patients with relapsed or refractory MM underwent a screening bone marrow or soft tissue biopsy. Sixteen patients were found to have sufficient plasma cells for HTS. Targeted next-generation sequencing was performed on plasma cell-free DNA from all patients who underwent HTS. RNA and whole-exome sequencing of bone marrow plasma cells were performed on eight and seven patients, respectively. RESULTS Results of HTS testing were made available to treating physicians within a median of 5 days from the biopsy. An actionable treatment result was identified in all 16 patients examined. Among the 13 patients who received assay-guided therapy, 92% achieved stable disease or better. The expression of 105 genes and mutations in 12 genes correlated with in vitro cytotoxicity. CONCLUSION In patients with relapsed or refractory MM, we demonstrate the feasibility of ex vivo drug sensitivity testing on isolated plasma cells from patient bone marrow biopsies or extramedullary plasmacytomas to inform the next line of therapy.
Confinement of bosonic and spinning particles in braneworlds
Authors: Souza F. E. A. , Alencar G. , Freitas L. F. F. , Landim R. R. 
Published: April 2021

Abstract
In this paper the confinement of bosonic and spinning test particles in smooth Randall-Sundrum models is studied. For this, we show the possibility of finding an effective potential that describes the motion of the particle over the extra dimension. For the bosonic case, it is a known fact that free test particles can be located neither on thin nor on thick branes. Recently, a coupling to a scalar field has been used to localize a limited range of masses. Up to now, no trapped test particles of any mass over the brane were found. In order to solve this, it is shown that a coupling with the dilaton may trap particles of any mass. Next, the spinning particle is analyzed. The spin variables,

, introduced an interaction with the Riemann curvature tensor. It introduced a correction to the effective potential. By analyzing it, it was found that the spinning particle may be localized at a different position from the one of the brane. It is also shown that a spinning particle over the brane may escape to infinity. Therefore, it is concluded that free bosonic and spinning particles are not trapped in the brane.
Universal scaling law for human-to-human transmission diseases
Authors: Francisco Cardoso Ben-Hur , Gonçalves Sebastián 
Published: April 2021

Abstract
Due to the COVID-19 pandemic, Susceptible-Infective-Recovered (SIR) models and their variants are in high demand for predicting the number of cases in urban areas. Aiming to correctly use the experience of the epidemic evolution from one local to another, we present an analysis of the transmission rate of COVID-19 as a function of population size at the metropolitan area level for the United States. Contrary to the usual hypothesis in epidemics modeling, we observe that the disease transmissibility scales with the logarithm of the local's population size. The analysis, made possible by a large amount of data available on simultaneous epidemics of the same type, is universal for any human-to-human transmission disease. We present a contact rate scaling theory that explains the results.
Plasma Cortisol and Risk of Atrial Fibrillation: A Mendelian Randomization Study
Authors: Larsson Susanna C , Lee Wei-Hsuan , Burgess Stephen , Allara Elias 
Published: April 2021

Abstract

Context
Atrial fibrillation (AF), cardiac arrhythmias, and related risk factors are common in patients with Cushing’s syndrome, or clinical chronic hypercortisolism. While hypercortisolism may be associated with AF, this association has not yet been ascertained causally.

Objective
To determine whether plasma cortisol is causally associated with AF using a 2-sample Mendelian randomization (MR) design.

Methods
Three genetic variants in the SERPINA1/SERPINA6 locus and functionally associated with plasma cortisol were identified in the CORtisol NETwork consortium (12 597 participants). Summary-level genome-wide association study (GWAS) data for the associations between the cortisol-associated variants and AF were obtained from a GWAS meta-analysis of 6 studies (60 620 AF cases and 970 216 noncases) and the FinnGen consortium (17 325 AF cases and 97 214 noncases). The fixed-effects inverse-variance weighted approach accounting for genetic correlations between variants was used for analysis. Multivariable MR analyses were conducted to assess potential mediating effects of systolic blood pressure (SBP) and waist circumference (WC). Summary-level GWAS data for SBP and WC were obtained respectively from the International Consortium of Blood Pressure (757 601 participants) and the Genetic Investigation of ANthropometric Traits consortium (232 101 participants).

Results
One standard deviation increase in genetically predicted plasma cortisol was associated with greater risk of AF (odds ratio [OR] 1.20, 95% CI 1.06-1.35). The association attenuated when adjusting for genetically predicted SBP and WC (OR 0.99, 95% CI 0.72-1.38).

Conclusion
Evidence derived from the MR study suggests a positive association between plasma cortisol and risk of AF, likely mediated through SBP and WC.