bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thermodynamic basis of the α-helix and DNA duplex
Authors: Dragan A. I. , Crane-Robinson C. , Privalov P. L. 
Published: April 2021

AbstractAnalysis of calorimetric and crystallographic information shows that the α-helix is maintained not only by the hydrogen bonds between its polar peptide groups, as originally supposed, but also by van der Waals interactions between tightly packed apolar groups in the interior of the helix. These apolar contacts are responsible for about 60% of the forces stabilizing the folded conformation of the α-helix and their exposure to water on unfolding results in the observed heat capacity increment, i.e. the temperature dependence of the melting enthalpy. The folding process is also favoured by an entropy increase resulting from the release of water from the peptide groups. A similar situation holds for the DNA double helix: calorimetry shows that the hydrogen bonding between conjugate base pairs provides a purely entropic contribution of about 40% to the Gibbs energy while the enthalpic van der Waals interactions between the tightly packed apolar parts of the base pairs provide the remaining 60%. Despite very different structures, the thermodynamic basis of α-helix and B-form duplex stability are strikingly similar. The general conclusion follows that the stability of protein folds is primarily dependent on internal atomic close contacts rather than the hydrogen bonds they contain.
Human leukocyte antigen I is significantly downregulated in patients with myxoid liposarcomas
Authors: Oike Naoki , Kawashima Hiroyuki , Ogose Akira , Hatano Hiroshi , Ariizumi Takashi , Yamagishi Tetsuro , Murayama Yudai , Umezu Hajime , Imai Chihaya , Hayashi Masanori , Endo Naoto 
Published: April 2021

AbstractThe characteristics of the tumor immune microenvironment remains unclear in liposarcomas, and here we aimed to determine the prognostic impact of the tumor immune microenvironment across separate liposarcomas subtypes. A total of 70 liposarcoma patients with three subtypes: myxoid liposarcoma (n = 45), dedifferentiated liposarcoma (n = 17), and pleomorphic liposarcoma (n = 8) were enrolled. The presence of tumor infiltrating lymphocytes (CD4+ , CD8+ , FOXP3+ lymphocytes) and CD163+ macrophages and expression of HLA class I and PD-L1 were assessed by immunohistochemistry in the diagnostic samples; overall survival and progression-free survival were estimated from outcome data. For infiltrating lymphocytes and macrophages, dedifferentiated liposarcoma and pleomorphic liposarcoma patients had a significantly higher number than myxoid liposarcoma patients. While myxoid liposarcoma patients with a high number of macrophages were associated with worse overall and progression-free survival, dedifferentiated liposarcoma patients with high macrophage numbers showed a trend toward favorable prognosis. Expression of HLA class I was negative in 35 of 45 (77.8%) myxoid liposarcoma tumors, whereas all dedifferentiated liposarcoma and pleomorphic liposarcoma tumors expressed HLA class I. The subset of myxoid liposarcoma patients with high HLA class I expression had significantly poor overall and progression-free survival, while dedifferentiated liposarcoma patients with high HLA class I expression tended to have favorable outcomes. Only four of 17 (23.5%) dedifferentiated liposarcomas, two of eight (25%) pleomorphic liposarcomas, and no myxoid liposarcoma tumors expressed PD-L1. Our results demonstrate the unique immune microenvironment of myxoid liposarcomas compared to other subtypes of liposarcomas, suggesting that the approach for immunotherapy in liposarcomas should be based on subtype.
Update on Incidence, Prevalence, Treatment and Survival of Patients with Small Bowel Neuroendocrine Neoplasms in the Netherlands
Authors: Kaçmaz Enes , Sarasqueta Arantza Farina , van Eeden Susanne , Dreijerink Koen M. A. , Klümpen Heinz‐Josef , Tanis Pieter J. , van Dijkum Els J. M. Nieveen , Engelsman Anton F. 
Published: April 2021

AbstractBackgroundSmall bowel neuroendocrine neoplasms (SB‐NEN) are rare cancers, population‐based studies are needed to study this rare indolent disease. The aim of this study was to explore trends in epidemiology, treatment and survival outcomes of patients with SB‐NEN based on Dutch nationwide data.Patients and methodsPatients with grade 1 or 2 SB‐NEN diagnosed between 2005 and 2015 were retrieved from the Netherlands Cancer Registry and linked to The Nationwide Network and Registry of Histo‐ and Cytopathology in the Netherlands. Age‐adjusted incidence rates were calculated based using the direct standardization method. Survival analyses were performed with the Kaplan–Meier method.ResultsA total of 1132 patients were included for epidemiological analyses. The age‐adjusted incidence rate of SB‐NEN increased from 0.52 to 0.81 per 100.000 person‐years between 2005 and 2015. Incidence was higher for males than females (0.93 vs. 0.69 in 2015). Most patients had grade 1 tumours (83%). Surgery was performed in 86% of patients, with resection of the primary tumour in 99%. During the study period, administration of somatostatin analogues (SSAs) increased from 5 to 22% for stage III and from 27 to 63% for stage IV disease. Mean follow‐up was 61 (standard deviation 38) months. Survival data were complete for 975/1132 patients and five‐year overall survival was 75% for stage I‐II, 75% for stage III and 57% for stage IV.ConclusionsThis study shows an increase in the incidence of SB‐NEN in the Netherlands. A predominant role of surgery was found in all disease stages. Use of SSAs has increased over time.
Assessing Differences in Lymph Node Metastasis Based Upon Sex in Early Non‐Small Cell Lung Cancer
Authors: Deng Han‐Yu , Liu Chang , Qiu Xiao‐Ming , Zhu Da‐Xing , Tang Xiao‐Jun , Zhou Qinghua 
Published: April 2021

AbstractBackgroundsWhether sex has any impact on the risk of lymph node (LN) metastasis (LNM) in patients with early‐stage non‐small cell lung cancer (NSCLC) remains controversial. Therefore, we aimed to objectively compared the risk of LNM between female and male patients with early‐stage NSCLC so as to figure out whether sex‐different extent of surgery may be justified for treating these patients.MethodsWe retrospectively collected clinical data of patients undergoing lobectomy or segmentectomy with systematic hilar and mediastinal LN dissection for clinical stage IA peripheral NSCLC from June 2014 to April 2019. Both multivariate logistic regression analysis and propensity score‐matched(PSM) analysis were applied to compare the risk of LNM between female and male patients.ResultsWe finally included a total of 660 patients for analysis. In the analysis of unmatched cohorts, there was no significant different rate of LNM (12.4% Vs 13.9%, P=0.556), hilar/intrapulmonary LNM (8.4% Vs 10.7%, P=0.318) and mediastinal LNM(7.9% Vs 7.5%, P=0.851) between female and male patients. In the multivariate analysis, sex was not found to be an independent predictor of LN in these patients. Moreover, in the analysis of well‐matched cohorts generated by PSM analysis, there was still no significant different rate of LNM (13.8% Vs 13.4%, P=0.892), hilar/intrapulmonary LNM (9.1% Vs 11.2%, P=0.442) and mediastinal LNM (9.1% Vs 6.5%, P=0.289) between female and male patients.ConclusionsSex was not an independent predictor of LNM in early‐stage NSCLC and there is no sufficient evidence justifying for sex‐different extent of surgical resection for these patients.
Diagnosing necrotizing external otitis on CT and MRI: assessment of pattern of extension
Authors: van der Meer Wilhelmina L. , Waterval Jérôme J. , Kunst Henricus P. M. , Mitea Cristina , Pegge Sjoert A. H. , Postma Alida A. 
Published: April 2021

Abstract
Background and purpose
Necrotizing external otitis (NEO) is a serious complication of external otitis. NEO can be classified according to—anterior, medial, posterior, intracranial, and contralateral—extension patterns. Currently there is no consensus on the optimal imaging modality for the identification of disease extension. This study compares NEO extension patterns on MR and CT to evaluate diagnostic comparability.

Methods
Patients who received a CT and MR within a 3-month interval were retrospectively examined. Involvement of subsites and subsequent spreading patterns were assessed on both modalities by a radiologist in training and by a senior head and neck radiologist. The prevalence of extension patterns on CT and MR were calculated and compared.

Results
All 21 included NEO cases showed an anterior extension pattern on CT and MR. Contrary to MR, medial extension was not recognized on CT in two out of six patients, and intracranial extension in five out of eight patients. The posterior extension pattern was not recognized on MR. Overall, single anterior extension pattern (62%) is more prevalent than multiple extension patterns (38%).

Conclusion
All anterior NEO extension pattern were identified on CT as well as MR. However, the medial and intracranial spreading patterns as seen on MR could only be identified on CT in a small number of patients. The posterior spreading pattern can be overlooked on MR. Thus, CT and MR are complimentary for the initial diagnosis and work-up of NEO as to correctly delineate disease extent through the skull base.
Nusinersen treatment in adult patients with spinal muscular atrophy: a safety analysis of laboratory parameters
Authors: Stolte Benjamin , Nonnemacher Michael , Kizina Kathrin , Bolz Saskia , Totzeck Andreas , Thimm Andreas , Wagner Bernd , Deuschl Cornelius , Kleinschnitz Christoph , Hagenacker Tim 
Published: April 2021

Abstract
Background
Nusinersen is an intrathecally administered antisense oligonucleotide (ASO) that improves motor function in patients with spinal muscular atrophy (SMA). In addition to efficacy, the safety of a therapy is the decisive factor for the success of the treatment. For some ASOs, various organ toxicities have been described, such as thrombocytopenia, renal and liver impairment, or coagulation abnormalities. However, systematic data on laboratory parameters under treatment with nusinersen are mainly available from studies in infants and children. Therefore, our aim was to assess the safety of nusinersen therapy in adult SMA patients.

Methods
Laboratory data from 404 nusinersen injections performed in 50 adult patients with SMA type 2 and type 3 were retrospectively analyzed.

Results
The total observation period was 76.9 patient-years, and patients received up to 12 injections. Our data provides no new safety concerns. In cerebrospinal fluid (CSF), the mean white blood cell count and lactate remained stable over time. Total CSF protein increased by 2.9 mg/dL. No change in mean platelet count was observed under therapy. Only one patient showed sporadic mild thrombocytopenia. Coagulation parameters and inflammatory markers were stable. The mean creatinine level decreased by 0.09 mg/dL. Analysis of mean liver enzyme levels revealed no relevant changes during treatment.

Conclusion
Our data demonstrate a favorable safety profile of nusinersen therapy in adult SMA patients under longer-term “real-world” conditions. In particular, we found no evidence of clinically relevant platelet declines, coagulopathies, or renal or hepatic organ toxicities, which are common concerns with the use of ASOs.
Endoscopic resection with adjuvant treatment versus esophagectomy for early-stage esophageal cancer
Authors: Huang Binhao , Xu Maria Christine , Pennathur Arjun , Li Zhigang , Liu Zhiguo , Wu Qi , Wang Jing , Luo Kongjia , Bai Jianying , Wei Zhi , Xiang Jiaqing , Fang Wentao , Zhang Jie 
Published: April 2021

Abstract
Objective
To evaluate the outcome following the strategy of endoscopic R0 resection (ER) plus adjuvant treatment (AT) versus esophagectomy for esophageal squamous cell cancer in T1a invading muscularis mucosa (M3)-T1b stage.

Methods
We evaluated the outcomes of 46 esophageal squamous cell cancer (ESCC) patients with T1aM3-T1b stage who underwent ER + AT from the Esophageal Cancer Endoscopic Therapy Consortium (ECETC) and compared these outcomes to 92 patients who underwent esophagectomy. Propensity score matching (1:2) was used, with overall survival (OS) and relapse-free survival (RFS) being compared between the two groups.

Results
During a median follow-up of 32 months, there were no statistical differences (P = 0.226) in OS between the two groups. The 1-, 2-, and 3-year overall survival in the esophagectomy group was 95%, 91%, and 84%, respectively. There were no mortalities within three years in the ER + AT group. The RFS between the two groups was also not significantly different (P = 0.938). The 1-, 2-, and 3-year RFS of patients in the esophagectomy group was 90%, 90%, and 83%, respectively, while it was 97%, 94%, and 74% in the ER + AT group, respectively. The local recurrence rates between the two groups were not significantly different (P = 0.277).

Conclusions
This first multicenter analysis showed similar outcomes were found regarding OS and RFS between the two groups in T1aM3-T1b stage patients. ER + AT may be considered in high-risk patients or for those who refuse esophagectomy.
Addition of high C:N crop residues to a P-limited substrate constrains the benefits of arbuscular mycorrhizal symbiosis for wheat P and N nutrition
Authors: Ingraffia Rosolino , Saia Sergio , Giovino Antonio , Amato Gaetano , Badagliacca Giuseppe , Giambalvo Dario , Martinelli Federico , Ruisi Paolo , Frenda Alfonso S. 
Published: April 2021

AbstractMany aspects concerning the role of arbuscular mycorrhizal (AM) fungi in plant nutrient uptake from organic sources remain unclear. Here, we investigated the contribution of AM symbiosis to N and P uptake by durum wheat after the addition of a high C:N biomass to a P-limited soil. Plants were grown in pots in the presence or absence of a multispecies AM inoculum, with (Org) or without (Ctr) the addition of 15N-labelled organic matter (OM). A further treatment, in which 15N was applied in mineral form (Ctr+N) in the same amount as that supplied in the Org treatment, was also included. Inoculation with AM had positive effects on plant growth in both control treatments (Ctr and Ctr+N), mainly linked to an increase in plant P uptake. The addition of OM, increasing the P available in the soil for the plants, resulted in a marked decrease in the contribution of AM symbiosis to plant growth and nutrient uptake, although the percentage of mycorrhization was higher in the Org treatment than in the controls. In addition, mycorrhization drastically reduced the recovery of 15N from the OM added to the soil whereas it slightly increased the N recovery from the mineral fertiliser. This suggests that plants and AM fungi probably exert a differential competition for different sources of N available in the soil. On the whole, our results provide a contribution to a better understanding of the conditions under which AM fungi can play an effective role in mitigating the negative effects of nutritional stresses in plants.
Experimental observations of aquifer storage and recovery in brackish aquifers using multiple partially penetrating wells
Authors: Witt Lilli , Müller Moritz J. , Gröschke Maike , Post Vincent E. A. 
Published: April 2021

AbstractAquifer storage and recovery systems using multiple partially penetrating wells (MPPW-ASR) can form a viable solution to the problem of freshwater buoyancy when using brackish aquifers for freshwater storage. This study presents the result of a series of laboratory experiments that aimed at visualizing the shape of freshwater bodies injected into a brackish aquifer and determining the effect on the recovery efficiency (RE) of several MPPW-ASR operational variables. A model aquifer was built in a Plexiglas tank using glass beads and water was injected and abstracted through point and vertical wells, which were operated in various combinations. Numerical models were used to support the interpretation of the time-lapse photographs, and showed that three-dimensional flow effects had to be considered for a correct interpretation of the visible dye patterns. Upward migration of both fresh (during injection) and brackish water (during recovery) along the vertical wells was observed, indicating that the role of well infrastructure as conduits is a critical design criterion for real-world systems. Gravitational instabilities formed when freshwater did not extend all the way to the top of the aquifer, and this negatively impacted the RE by causing greater mixing. The positive freshwater buoyancy led to freshwater bodies that became narrower with depth, and the formation of thin, elongated buffer zones along the aquifer top in multicycle experiments. Up-coning below abstraction wells resulted in lower RE values, reinforcing the potential of scavenger wells to enhance MPPW-ASR system performance.
Development of the surface displacement velocity in a full-scale loamy model slope under multistep excavation
Authors: Sasahara Katsuo , Hiraoka Nobutaka , Kikkawa Naotaka , Itoh Kazuya 
Published: April 2021

AbstractMultistep excavations were implemented at the toe of a large-scale slope model, and the surface displacements in the slope were measured to examine the validity of the relationship between the velocity and acceleration proposed by Fukuzono for excavated slopes. The surface displacement increased both during and after slope excavation, among which the latter was due to creep deformation under a constant stress. The rate of increase in the surface displacement was initially high and then decreased to zero during creep deformation after the excavation without slope failure. However, the surface displacement exhibited an accelerated increase during creep deformation after the final excavation prior to slope failure; the surface displacement increased with small fluctuations even before slope failure occurred. The surface displacement velocity and acceleration also fluctuated notably due to variations in the surface displacement. The trendlines for the derived relationships between the velocity and acceleration were in good general agreement with the measured data at certain locations in the model slope. These relationships were unique at different locations on the slope, while the inclination of the relationship trendline suddenly decreased just prior to slope failure. The steeper trendlines predicted an earlier failure time if the displacement was large and close to the failure condition, whereas they resulted in worse predictions if the displacement was small and far from causing slope failure according to the prediction method proposed by Fukuzono.
Determination of initial airtightness after anatomical laser segmentectomy in an ex vivo model
Authors: Kirschbaum Andreas , Ivanovic Andrijana , Wiesmann Thomas , Mirow Nikolas , Meyer Christian 
Published: April 2021

AbstractIf a pulmonary pathology can be removed by anatomical segmentectomy, the need for lobectomy is obviated. The procedure is considered oncologically equivalent and saves healthy lung tissue. In every segmentectomy, lung parenchyma must be transected in the intersegmental plane. Using an ex vivo model based on porcine lung, three transection techniques (monopolar cutter + suture, stapler, and Nd:YAG laser) are to be compared with respect to their initial airtightness. At an inspiratory ventilation pressure of 25 mbar, all three preparations were airtight. Upon further increase in ventilation pressure up to 40 mbar, the laser group performed best in terms of airtightness. Since thanks to its use of a laser fibre, this technique is particularly suitable for minimally invasive surgery; it should be further evaluated clinically for this indication in the future.
A pulsed-Laser Rb atomic frequency standard for GNSS applications
Authors: Micalizio S. , Levi F. , Calosso C. E. , Gozzelino M. , Godone A. 
Published: April 2021

AbstractWe present the results of 10 years of research related to the development of a Rubidium vapor cell clock based on the principle of pulsed optical pumping (POP). Since in the pulsed approach, the clock operation phases take place at different times, this technique demonstrated to be very effective in curing several issues affecting traditional Rb clocks working in a continuous regime, like light shift, with a consequent improvement of the frequency stability performances. We describe two laboratory prototypes of POP clock, both developed at INRIM. The first one achieved the best results in terms of frequency stability: an Allan deviation of σy(τ) = 1.7 × 10−13 τ−1/2, being τ the averaging time, has been measured. In the prospect of a space application, we show preliminary results obtained with a second more recent prototype based on a loaded cavity-cell arrangement. This clock has a reduced size and exhibited an Allan deviation of σy(τ) = 6 × 10−13 τ−1/2, still a remarkable result for a vapor cell device. In parallel, an ongoing activity performed in collaboration with Leonardo S.p.A. and aimed at developing an engineered space prototype of the POP clock is finally mentioned. Possible issues related to space implementation are also briefly discussed. On the basis of the achieved results, the POP clock represents a promising technology for future GNSSs.
A model and algorithm for identifying driver pathways based on weighted non-binary mutation matrix
Authors: Wu Jingli , Zhu Kai , Li Gaoshi , Wang Jinyan , Cai Qirong 
Published: April 2021

AbstractIt is generally acknowledged that driver pathway plays a decisive role in the occurrence and progress of tumors, and the identification of driver pathways has become imperative for precision medicine or personalized medicine. Due to the inevitable sequencing error, the noise contained in single omics cancer data usually plays a negative effect on identification. It is a feasible approach to take advantage of multi-omics cancer data rather than a single one now that large amounts of multi-omics cancer data have become available. The identification of driver pathways by integrating multi-omics cancer data has attracted attention of researchers in bioinformatics recently. In this paper, a weighted non-binary mutation matrix is constructed by integrating copy number variations, somatic mutations and gene expressions. Based on the weighted non-binary mutation matrix, a new identification model is proposed through defining new measurements of coverage and exclusivity. Then, a cooperative coevolutionary algorithm CGA-MWS is put forward for solving the presented model. Both real cancer data and simulated one were used to conduct comparisons among methods Dendrix, GA, iMCMC, MOGA, PGA-MWS and CGA-MWS. Compared with the pathways identified by the other five methods, more genes, belonging to the pathway identified by the CGA-MWS method, are enriched in a known signaling pathway in most cases. Simultaneously, the high efficiency of method CGA-MWS makes it practical in realistic applications. All of which have been verified through a number of experiments.