bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of Plasmodium falciparum anti-malarial drug resistance markers in pfk13-propeller, pfcrt and pfmdr1 genes in isolates from treatment failure patients in Democratic Republic of Congo, 2018–2019
Authors: Yobi Doudou M. , Kayiba Nadine K. , Mvumbi Dieudonné M. , Boreux Raphael , Kabututu Pius Z. , Situakibanza Hippolyte N. T. , Umesumbu Solange E. , De Mol Patrick , Speybroeck Niko , Mvumbi Georges L. , Hayette Marie-Pierre 
Published: March 2021

Abstract
Background
The national policy for malaria treatment of the Democratic Republic of Congo recommends two first-line artemisinin-based combinations for the treatment of uncomplicated malaria: artesunate-amodiaquine and artemether-lumefantrine. This study investigated the presence of markers associated with resistance to the current first-line artemisinin-based combination therapy (ACT) in isolates of Plasmodium falciparum from treatment failure patients in the Democratic Republic of Congo.

Methods
From November 2018 to November 2019, dried blood spots were taken from patients returning to health centres for fever within 28 days after an initial malaria treatment in six sentinel sites of the National Malaria Control Programme across Democratic Republic of Congo. The new episode of malaria was first detected by a rapid diagnostic test and then confirmed by a real-time PCR assay to define treatment failure. Fragments of interest in pfk13 and pfcrt genes were amplified by conventional PCR before sequencing and the Pfmdr1 gene copy number was determined by a TaqMan real-time PCR assay.

Results
Out of 474 enrolled patients, 364 (76.8%) were confirmed positive by PCR for a new episode of P. falciparum malaria, thus considered as treatment failure. Of the 325 P. falciparum isolates obtained from 364 P. falciparum-positive patients and successfully sequenced in the pfk13-propeller gene, 7 (2.2%) isolates carried non-synonymous mutations, among which 3 have been previously reported (N498I, N554K and A557S) and 4 had not yet been reported (F506L, E507V, D516E and G538S). Of the 335 isolates successfully sequenced in the pfcrt gene, 139 (41.5%) harboured the K76T mutation known to be associated with chloroquine resistance. The SVMNT haplotype associated with resistance to amodiaquine was not found. None of the isolates carried an increased copy number of the pfmdr1 gene among the 322 P. falciparum isolates successfully analysed.

Conclusion
No molecular markers currently known to be associated with resistance to the first-line ACT in use were detected in isolates of P. falciparum from treatment failure patients. Regular monitoring through in vivo drug efficacy and molecular studies must continue to ensure the effectiveness of malaria treatment in Democratic Republic of Congo.
Upregulation of ACE2 and TMPRSS2 by particulate matter and idiopathic pulmonary fibrosis: a potential role in severe COVID-19
Authors: Li Hsin-Hsien , Liu Chen-Chi , Hsu Tien-Wei , Lin Jiun-Han , Hsu Jyuan-Wei , Li Anna Fen-Yau , Yeh Yi-Chen , Hung Shih-Chieh , Hsu Han-Shui 
Published: March 2021

Abstract
Background
Air pollution exposure and idiopathic pulmonary fibrosis (IPF) cause a poor prognosis after SARS-CoV-2 infection, but the underlying mechanisms are not well explored. Angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are the keys to the entry of SARS-CoV-2. We therefore hypothesized that air pollution exposure and IPF may increase the expression of ACE2 and TMPRSS2 in the lung alveolar region. We measured their expression levels in lung tissues of control non-IPF and IPF patients, and used murine animal models to study the deterioration of IPF caused by particulate matter (PM) and the molecular pathways involved in the expression of ACE2 and TMPRSS2.

Results
In non-IPF patients, cells expressing ACE2 and TMPRSS2 were limited to human alveolar cells. ACE2 and TMPRSS2 were largely upregulated in IPF patients, and were co-expressed by fibroblast specific protein 1 (FSP-1) + lung fibroblasts in human pulmonary fibrotic tissue. In animal models, PM exposure increased the severity of bleomycin-induced pulmonary fibrosis. ACE2 and TMPRSS2 were also expressed in FSP-1+ lung fibroblasts in bleomycin-induced pulmonary fibrosis, and when combined with PM exposure, they were further upregulated. The severity of pulmonary fibrosis and the expression of ACE2 and TMPRSS2 caused by PM exposure were blocked by deletion of KC, a murine homologue of IL-8, or treatment with reparixin, an inhibitor of IL-8 receptors CXCR1/2.

Conclusions
These data suggested that risk of SARS-CoV-2 infection and COVID-19 disease severity increased by air pollution exposure and underlying IPF. It can be mediated through upregulating ACE2 and TMPRSS2 in pulmonary fibroblasts, and prevented by blocking the IL-8/CXCR1/2 pathway.
Next-generation sequencing facilitates differentiating between multiple primary lung cancer and intrapulmonary metastasis: a case series
Authors: Liu Changjiang , Liu Chengang , Zou Xiao , Shao Lin , Sun Ying , Guo Yang 
Published: March 2021

Abstract
Background
In lung cancer management, differential diagnosis between multiple primary lung cancer (MPLC) and intrapulmonary metastasis (IMP) is a critical point that is of direct therapeutic and clinical importance. However, this process often suffers from absence of a gold standard, resulting in equivocal cases. Herein, we present a series of three cases, in which genomic alteration patterns revealed by next-generation sequencing (NGS) facilitated the differential diagnosis between MPLC and IMP.

Case presentation
Case 1 was a 57-year-old female with two separate lesions in the upper lobe and the lower lobe of left lung, which were both histopathologically determined as T2aN0M0 adenocarcinomas. NGS identified an EGFR L858R in one lesion and an EGFR 20 exon insertion in the other one, suggestive of double primary malignancies. The patient underwent wedge resections and received an adjuvant treatment of icotinib and chemotherapy. She had a disease-free survival (DFS) of 19 months and counting. Case 2 was a 55-year-old female with multiple small lesions in both lungs. Histopathological examinations of resected lesions from right upper lobe revealed three subtypes: atypical adenomatous hyperplasia of alveolar epithelium, adenocarcinomas in situ and minimally invasive adenocarcinoma. NGS identified two different BRAF driver mutations G466E and V600_K601delinsE in two lesions of adenocarcinoma in situ, and a BRAF K601E in a lesion of minimally invasive adenocarcinoma. Case 3, a 68-year-old male, had the right upper lobe lesion histophathologically classified as a stage T3NxM0 mixed adenoneuroendocrine carcinoma and the left upper lobe lesion as a stage T1aN0M0 adenocarcinoma. NGS performed with different loci of surgical tissues revealed a rare sensitizing EGFR mutation G719A shared by the right upper lobe lesion and lymph node, and two EGFR mutations L861Q and G719S in left upper lobe lesion. The patient received icotinib treatment postoperatively and achieved a stable disease with a progression-free survival of 5 months.

Conclusion
Our cases provide evidence for utility of NGS in facilitating diagnosis and treatment decisions.
Guided growth in the correction of knee deformity in patients with congenital insensitivity to pain
Authors: Baghdadi Soroush , Saberi Sadegh , Baghdadi Taghi 
Published: March 2021

Abstract
Background
Orthopedic manifestations of congenital insensitivity to pain (CIP) can be devastating if left untreated. Knee deformities are common in patients with CIP and might lead to joint destruction and loss of walking ability. The purpose of the present study was to report the results and complications of guided growth procedures around the knee in patients with CIP.

Methods
In a retrospective review, all patients with CIP who underwent guided growth procedures around the knee from 2009 to 2017 at a tertiary referral hospital were evaluated. Patients with secondary insensitivity to pain (e.g., syringomyelia), as well as patients with incomplete records, were excluded. Demographic data, clinical findings, correction rate, and complications were recorded.

Results
Ten knees in six patients fulfilled the inclusion criteria. The median age was 10 (range, 5–12), with a mean follow-up of 31 months (range, 16–56). Distal femoral tension-band hemiepiphysiodesis was the most common procedure, followed by proximal tibial hemiepiphysiodesis. The mean correction rate was 0.28°/month for femoral deformity. Staples were removed prematurely in one patient due to extrusion. No cases of infection or skin dehiscence were observed. None of the patients needed a reconstructive knee procedure during the study period.

Conclusions
The findings of this study suggest that guided growth procedures might have a role in the correction of knee deformities in patients with CIP. However, the correction rate is lower than that of typically developing children, patients should be closely followed to prevent complications, and stringent patient selection criteria should be followed to ensure success.
Correction to: The lncRNA LAMP5-AS1 drives leukemia cell stemness by directly modulating DOT1L methyltransferase activity in MLL leukemia
Authors: Wang Wen-Tao , Chen Tian-Qi , Zeng Zhan-Cheng , Pan Qi , Huang Wei , Han Cai , Fang Ke , Sun Lin-Yu , Yang Qian-Qian , Wang Dan , Luo Xue-Qun , Sun Yu-Meng , Chen Yue-Qin 
Published: March 2021

The original article [1] contains an error in Fig. 6b for the image of western blot panels.
ROS-dependent HIF1α activation under forced lipid catabolism entails glycolysis and mitophagy as mediators of higher proliferation rate in cervical cancer cells
Authors: Castelli Serena , Ciccarone Fabio , Tavian Daniela , Ciriolo Maria Rosa 
Published: March 2021

Abstract
Background
In the last decades, the concept of metabolic rewiring as a cancer hallmark has been expanded beyond the “Warburg effect” and the importance of other metabolic routes, including lipid metabolism, has emerged. In cancer, lipids are not only a source of energy but are also required for the formation of membranes building blocks, signaling and post-translational modification of proteins. Since lipid metabolism contributes to the malignancy of cancer cells, it is an attractive target for therapeutic strategies.

Methods
Over-expression of the adipose triglyceride lipase (ATGL) was used to boost lipid catabolism in cervical cancer cells. The cervical cancer cell line HeLa was employed as the primary experimental model for all subsequent studies. The lipolytic activity of ATGL was mimicked by caproate, a short-chain fatty acid that is efficiently oxidized in mitochondria.

Results
Here, we provide evidence of the association between boosted lipid catabolism and the increased proliferation and migration capability of cervical cancer cells. These pro-tumoral effects were ascribed to the reactive oxygen species (ROS)-mediated induction of hypoxia-inducible factor-1α (HIF1α) triggered by the increased mitochondrial fatty acids (FAs) oxidation. HIF1α activation increases glycolytic flux and lactate production, promoting cell proliferation. At the same time, HIF1α increases protein and mRNA levels of its known target BCL2 and adenovirus E1B 19-kDa-interacting protein 3 (BNIP3), which in turn activates mitophagy as a pro-survival process, as demonstrated by the induction of apoptosis upon inhibition of mitophagy. These effects were mimicked by the short-chain fatty acid caproate, confirming that forcing lipid catabolism results in HIF1α induction.

Conclusions
Boosting lipid catabolism by ATGL over-expression has a pro-tumor role in cervical cancer cells, dependent on ROS production and HIF1α induction. Together with the bioinformatics evidence of the correlation of ATGL activity with the aggressiveness of cervical cancer cells, our data suggest that ATGL could be a promising prognostic marker for cervical cancer and highlight the need of further investigations on the role of this lipase in cancer cells. This evidence could be exploited to develop new personalized therapy, based on the functionality of the antioxidant equipment of cancer cells, considering that ROS content could affect ATGL role.
Evaluation of whole-body modalities for diagnosis of multifocal osteonecrosis—a pilot study
Authors: Yokota Shunichi , Sakamoto Keita , Shimizu Yukie , Asano Tsuyoshi , Takahashi Daisuke , Kudo Kohsuke , Iwasaki Norimasa , Shimizu Tomohiro 
Published: March 2021

AbstractBackgroundThis study aimed to investigate the ability of whole-body bone scintigraphy (WB-BS) in the detection of multifocal osteonecrosis (ON) compared to whole-body magnetic resonance imaging (WB-MRI) and to clarify the characteristics of patients with multifocal ON among those with ON of the femoral head (ONFH) using WB-MRI.MethodsForty-six patients who had symptomatic ONFH and underwent surgery in our hospital from April 2019 to October 2020 were included in the study. Data on patient demographics, including age, sex, body mass index (BMI), history of corticosteroid intake, alcohol abuse, smoking, and symptomatic joints, were collected from their medical records. All patients underwent WB-MRI and WB-BS before surgery.ResultsThe agreement in the detection of ON by WB-MRI vs the uptake lesions by WB-BS in the hip joints was moderate (κ = 0.584), while that in other joints was low (κ < 0.40). Among the 152 joints with ON detected by WB-MRI, 92 joints (60.5%) were symptomatic, and 60 joints (39.5%) were asymptomatic. Twelve out of the 46 (26.0%) patients had multifocal (three or more distinct anatomical sites) ON. Nonetheless, while WB-BS detected symptomatic ON detected by WB-MRI as uptake lesions in 82.6% (76/92) of the joints, asymptomatic ON detected by WB-MRI was detected as uptake lesions in 21.7% (13/60) of the joints. All patients with multifocal ON had a history of steroid therapy, which was significantly higher than that in patients with oligofocal ON (P = 0.035). The patients with a hematologic disease had multifocal ON at a higher rate (P = 0.015).ConclusionsIt might be difficult for WB-BS to detect the asymptomatic ON detected by WB-MRI compared to symptomatic ON. Considering the cost, examination time, and radiation exposure, WB-MRI might be useful for evaluating multifocal ON. Larger longitudinal studies evaluating the benefits of WB-MRI for detecting the risk factors for multifocal ON are required.
Emerging role of 18F-FDG PET/CT in Castleman disease: a review
Authors: Koa Benjamin , Borja Austin J. , Aly Mahmoud , Padmanabhan Sayuri , Tran Joseph , Zhang Vincent , Rojulpote Chaitanya , Pierson Sheila K. , Tamakloe Mark-Avery , Khor Johnson S. , Werner Thomas J. , Fajgenbaum David C. , Alavi Abass , Revheim Mona-Elisabeth 
Published: March 2021

AbstractCastleman disease (CD) describes a group of rare hematologic conditions involving lymphadenopathy with characteristic histopathology and a spectrum of clinical abnormalities. CD is divided into localized or unicentric CD (UCD) and multicentric CD (MCD) by imaging. MCD is further divided based on etiological driver into human herpesvirus-8-associated MCD, POEMS-associated MCD, and idiopathic MCD. There is notable heterogeneity across MCD, but increased level of pro-inflammatory cytokines, particularly interleukin-6, is an established disease driver in a portion of patients. FDG-PET/CT can help determine UCD versus MCD, evaluate for neoplastic conditions that can mimic MCD clinico-pathologically, and monitor therapy responses. CD requires more robust characterization, earlier diagnosis, and an accurate tool for both monitoring and treatment response evaluation; FDG-PET/CT is particularly suited for this. Moving forward, future prospective studies should further characterize the use of FDG-PET/CT in CD and specifically explore the utility of global disease assessment and dual time point imaging.Trial registrationClinicalTrials.gov, NCT02817997, Registered 29 June 2016,https://clinicaltrials.gov/ct2/show/NCT02817997
On the achievable rate of bandlimited continuous-time AWGN channels with 1-bit output quantization
Authors: Bender Sandra , Dörpinghaus Meik , Fettweis Gerhard P. 
Published: March 2021

AbstractWe consider a real continuous-time bandlimited additive white Gaussian noise channel with 1-bit output quantization. On such a channel the information is carried by the temporal distances of the zero-crossings of the transmit signal. We derive an approximate lower bound on the capacity by lower-bounding the mutual information rate for input signals with exponentially distributed zero-crossing distances, sine-shaped transition waveform, and an average power constraint. The focus is on the behavior in the mid-to-high signal-to-noise ratio (SNR) regime above 10 dB. For hard bandlimited channels, the lower bound on the mutual information rate saturates with the SNR growing to infinity. For a given SNR the loss with respect to the unquantized additive white Gaussian noise channel solely depends on the ratio of channel bandwidth and the rate parameter of the exponential distribution. We complement those findings with an approximate upper bound on the mutual information rate for the specific signaling scheme. We show that both bounds are close in the SNR domain of approximately 10–20 dB.
FGF gene expression in injured tendons as a prognostic biomarker of 1-year patient outcome after Achilles tendon repair
Authors: Chen Junyu , Svensson Joel , Sundberg Carl-Johan , Ahmed Aisha Siddiqah , Ackermann Paul W. 
Published: March 2021

Abstract
Purpose
Healing outcome after Achilles Tendon Rupture (ATR) is variable and unsatisfactory. Many ATR patients still exhibit pain, functional deficits and limitations in walking one-year post-surgery. The present study was designed to investigate the association between the expression of healing biomarkers and patient outcome after ATR.

Methods
Tendon biopsies were collected from 25 ATR patients during surgery. At 1-year post surgery, all patients completed questionnaires; Achilles tendon Total Rupture Score (ATRS) and Foot and Ankle Outcome Score (FAOS), and were tested for functional outcomes by heel-rise test. In biopsies, FGF, COL III, FN, COL I and MMP-9 mRNA levels were assessed by quantitative RT-PCR while protein expression was studied by immunohistochemistry (IHC).

Results
Our analysis confirmed the presence of FGF, COL III, FN, COL I and MMP-9 at mRNA and protein levels in tendon biopsies. FGF gene expression associated positively with improved total ATRS and better functional outcomes. Additionally, FGF mRNA levels were associated with less pain, less running limitations and less loss in physical activity. In addition, higher COL III mRNA expression was associated with more tendon strength.

Conclusion
Our findings indicate that FGF gene expression is associated with improved patient-reported outcome. FGF expression in surgical biopsies could potentially be used to assist the prognostic evaluation of patient outcome and may be used as a predictor for healing. However, further studies are needed to evaluate the role of FGF in Achilles tendon healing.

Level of evidence
II
Content validity and psychometric evaluation of the Functional Assessment of Chronic Illness Therapy-Fatigue scale in patients with chronic lymphocytic leukemia
Authors: Eek Daniel , Ivanescu Cristina , Corredoira Laura , Meyers Oren , Cella David 
Published: March 2021

Abstract
Purpose
Fatigue is a prominent symptom in individuals with chronic lymphocytic leukemia (CLL). This work evaluates the content validity and psychometric properties of the Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-Fatigue) in patients with CLL to determine if it is fit for purpose in CLL research.

Methods
The FACIT-Fatigue yields a 13-item total score from a five-item symptom subscale and an eight-item impact subscale. To evaluate content validity, cognitive debriefing interviews were conducted with 40 patients with CLL in the first-line or relapsed or refractory setting. Psychometric properties, including structural validity, internal consistency, construct and known-groups validity, were investigated using data from a phase 3 trial in relapsed or refractory CLL (NCT02970318).

Results
Interviewed patients considered the FACIT-Fatigue items relevant to their CLL experience, understood the terminology and agreed with response options. Confirmatory factor analysis confirmed the presence of symptom and impact subscales, but also supported unidimensionality of the FACIT-Fatigue. The FACIT-Fatigue total, symptom and impact subscales demonstrated good internal consistency (Cronbach’s coefficient α > 0.85 and McDonald’s omega ω > 0.90), and strong correlations with relevant EORTC QLQ-C30 scales (all Spearman’s r ≥ 0.5). Known-groups validity was shown by significant differences between groups defined by baseline performance status, hemoglobin level and constitutional symptoms (all p < .0001). Cluster analysis supported FACIT-Fatigue score thresholds of 30 and 34 to define a severe fatigue population.

Conclusions
Content validity and psychometric evaluation in patients with CLL demonstrated that the FACIT-Fatigue has good psychometric properties and is fit for purpose in CLL.
Cavity detection by SH-wave full-waveform inversion — A reflection-focused approach
Authors: Mecking Rebekka , Köhn Daniel , Meinecke Matthias , Rabbel Wolfgang 
Published: March 2021

The detection of cavities with geophysical methods is a challenging task for which a general approach has not yet been found. We have found that viscoelastic SH full-waveform inversion (FWI), focusing primarily on reflection events, is able to accurately locate the position of cavities, areas of decompacted sediments, and, more generally, seismic low-velocity anomalies down to 30 m depth. The key for a successful FWI application is the enhancement of the reflected wavefield relative to the surface wavefield. For this purpose, we apply automatic gain control normalization in the objective function. By focusing the inversion on the reflected wavefield, we determine that one can differentiate between air-filled cavities with zero shear-wave (S-wave) velocity and low-velocity zones. Additionally, we test the FWI approach on a field data set, with a known collapsed tunnel system inside a 32 m high monumental antique grave mound. The results show that the location and extent, as well as the density and S-wave velocity of the collapsed tunnel system, can be determined with sufficient accuracy by applying a 2D FWI approach to intersecting profiles, despite the 3D nature of the problem.
Numerical study of crosshole electromagnetic tunnel detection
Authors: Neese John W. , Jackson David R. , Zheng Yingcai , Thomsen Leon A. 
Published: March 2021

Electromagnetic tunnel detection is studied numerically using a 3D analytic infinite lossy homogeneous space solution to magnetic dipole radiation and scattering from an infinite cylinder, in a crosshole context. At low frequencies, this serves as a model for a transmit coil radiating a time-varying magnetic field that is then detected from the open-circuit voltage induced on a receive coil. Numerical simulations illustrate how various parameters influence the signal strength and the ability to discern the scattered signal. Tunnel detection is achieved at relatively high frequencies (but below typical ground-penetrating radar frequencies) for fresh water-saturated sand and for weathered granite, which are lower loss media; for the coil and tunnel parameters used here, the optimum frequencies appear to be between 100 kHz and 1 MHz. Tunnel detection for fresh water-saturated clay, a much more lossy medium, can be achieved at a quite low frequency, with an optimum frequency between 1 and 10 kHz. These results suggest that, when a resonant coil system is used, tunnel detection may be possible in a wider range of earth media than previously reported, when the best-suited choice of frequency is used.