bluuebunny/crossref_metadata_2025 huggingface dataset:
AXDND1, a novel testis-enriched gene, is required for spermiogenesis and male fertility
Authors: Ma Qian , Cao Congcong , Zhuang Changshui , Luo Xiaomin , Li Xiaofeng , Wan Huijuan , Ye Jing , Chen Fangfang , Cui Lina , Zhang Yan , Wen Yujiao , Yuan Shuiqiao , Gui Yaoting
Published: November 2021

Spermiogenesis is a complex process depending on the sophisticated coordination of a myriad of testis-enriched gene regulations. The regulatory pathways that coordinate this process are not well understood, and we demonstrate here that AXDND1, as a novel testis-enriched gene is essential for spermiogenesis and male fertility. AXDND1 is exclusively expressed in the round and elongating spermatids in humans and mice. We identified two potentially deleterious mutations of AXDND1 unique to non‐obstructive azoospermia (NOA) patients through selected exonic sequencing. Importantly,Axdnd1knockout males are sterile with reduced testis size caused by increased germ cell apoptosis and sloughing, exhibiting phenotypes consistent with oligoasthenoteratozoospermia.Axdnd1mutated late spermatids showed head deformation, outer doublet microtubules deficiency in the axoneme, and loss of corresponding accessory structures, including outer dense fiber (ODF) and mitochondria sheath. These phenotypes were probably due to the perturbed behavior of the manchette, a dynamic structure where AXDND1 was localized. Our findings establish AXDND1 as a novel testis-enrich gene essential for spermiogenesis and male fertility probably by regulating the manchette dynamics, spermatid head shaping, sperm flagellum assembly.
A short hepatitis C virus NS5A peptide expression by AAV vector modulates human T cell activation and reduces vector immunogenicity
Authors: Colon-Moran Winston , Baer Alan , Lamture Gauri , Stapleton Jack T. , Fischer Joseph W. , Bhattarai Nirjal
Published: November 2021

Viral vector-mediated gene therapies have the potential to treat many human diseases; however, host immune responses against the vector and/or the transgene pose a safety risk to the patients and can negatively impact product efficacy. Thus, novel strategies to reduce vector immunogenicity are critical for the advancement of these therapies. T cell activation (TCA) is required for the development of immune responses during gene therapy. We hypothesized that modulation of TCA by incorporating a novel viral immunomodulatory factor into a viral vector may reduce unwanted TCA and immune responses during gene therapy. To test this hypothesis, we identified an immunomodulatory domain of the hepatitis C virus (HCV) NS protein 5A (NS5A) protein and studied the effect of viral vectors expressing NS5A peptide on TCA. Lentiviral vector-mediated expression of a short 20-mer peptide derived from the NS5A protein in human T cells was sufficient to inhibit TCA. Synthetic 20-mer NS5A peptide also inhibited TCA in primary human T cells. Mechanistically, the NS5A protein interacted with Lck and inhibited proximal TCR signaling. Importantly, NS5A peptide expression did not cause global T cell signaling dysfunction as distal T cell signaling was not inhibited. Finally, recombinant adeno-associated virus (AAV) vector expressing the 20-mer NS5A peptide reduced both the recall antigen and the TCR-mediated activation of human T cells and did not cause global T cell signaling dysfunction. Together, these data suggest that expression of a 20-mer NS5A peptide by an AAV vector may reduce unwanted TCA and may contribute to lower vector immunogenicity during gene therapy.
A tissue-bioengineering strategy for modeling rare human kidney diseases in vivo
Authors: Hernandez J. O. R. , Wang X. , Vazquez-Segoviano M. , Lopez-Marfil M. , Sobral-Reyes M. F. , Moran-Horowich A. , Sundberg M. , Lopez-Cantu D. O. , Probst C. K. , Ruiz-Esparza G. U. , Giannikou K. , Abdi R. , Henske E. P. , Kwiatkowski D. J. , Sahin M. , Lemos D. R.
Published: November 2021

The lack of animal models for some human diseases precludes our understanding of disease mechanisms and our ability to test prospective therapies in vivo. Generation of kidney organoids from Tuberous Sclerosis Complex (TSC) patient-derived-hiPSCs allows us to recapitulate a rare kidney tumor called angiomyolipoma (AML). Organoids derived from TSC2−/− hiPSCs but not from isogenic TSC2+/− or TSC2+/+ hiPSCs share a common transcriptional signature and a myomelanocytic cell phenotype with kidney AMLs, and develop epithelial cysts, replicating two major TSC-associated kidney lesions driven by genetic mechanisms that cannot be consistently recapitulated with transgenic mice. Transplantation of multiple TSC2−/− renal organoids into the kidneys of immunodeficient rats allows us to model AML in vivo for the study of tumor mechanisms, and to test the efficacy of rapamycin-loaded nanoparticles as an approach to rapidly ablate AMLs. Collectively, our experimental approaches represent an innovative and scalable tissue-bioengineering strategy for modeling rare kidney disease in vivo.
Focal amplifications are associated with chromothripsis events and diverse prognoses in gastric cardia adenocarcinoma
Authors: Zhao Xue-Ke , Xing Pengwei , Song Xin , Zhao Miao , Zhao Linxuan , Dang Yonglong , Lei Ling-Ling , Xu Rui-Hua , Han Wen-Li , Wang Pan-Pan , Yang Miao-Miao , Hu Jing-Feng , Zhong Kan , Zhou Fu-You , Han Xue-Na , Meng Chao-Long , Ji Jia-Jia , Chen Xingqi , Wang Li-Dong
Published: November 2021

The role of focal amplifications and extrachromosomal DNA (ecDNA) is unknown in gastric cardia adenocarcinoma (GCA). Here, we identify frequent focal amplifications and ecDNAs in Chinese GCA patient samples, and find focal amplifications in the GCA cohort are associated with the chromothripsis process and may be induced by accumulated DNA damage due to local dietary habits. We observe diverse correlations between the presence of oncogene focal amplifications and prognosis, where ERBB2 focal amplifications positively correlate with prognosis and EGFR focal amplifications negatively correlate with prognosis. Large-scale ERBB2 immunohistochemistry results from 1668 GCA patients show survival probability of ERBB2 positive patients is lower than that of ERBB2 negative patients when their surviving time is under 2 years, however, the tendency is opposite when their surviving time is longer than 2 years. Our observations indicate that the ERBB2 focal amplifications may represent a good prognostic marker in GCA patients.
Discordant associations of educational attainment with ASD and ADHD implicate a polygenic form of pleiotropy
Authors: Verhoef Ellen , Grove Jakob , Shapland Chin Yang , Demontis Ditte , Burgess Stephen , Rai Dheeraj , Børglum Anders D. , St Pourcain Beate
Published: November 2021

Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) are complex co-occurring neurodevelopmental conditions. Their genetic architectures reveal striking similarities but also differences, including strong, discordant polygenic associations with educational attainment (EA). To study genetic mechanisms that present as ASD-related positive and ADHD-related negative genetic correlations with EA, we carry out multivariable regression analyses using genome-wide summary statistics (N = 10,610–766,345). Our results show that EA-related genetic variation is shared across ASD and ADHD architectures, involving identical marker alleles. However, the polygenic association profile with EA, across shared marker alleles, is discordant for ASD versus ADHD risk, indicating independent effects. At the single-variant level, our results suggest either biological pleiotropy or co-localisation of different risk variants, implicating MIR19A/19B microRNA mechanisms. At the polygenic level, they point to a polygenic form of pleiotropy that contributes to the detectable genome-wide correlation between ASD and ADHD and is consistent with effect cancellation across EA-related regions.
Deciphering intratumoral heterogeneity using integrated clonal tracking and single-cell transcriptome analyses
Authors: Contreras-Trujillo Humberto , Eerdeng Jiya , Akre Samir , Jiang Du , Contreras Jorge , Gala Basia , Vergel-Rodriguez Mary C. , Lee Yeachan , Jorapur Aparna , Andreasian Areen , Harton Lisa , Bramlett Charles S. , Nogalska Anna , Xiao Gang , Lee Jae-Woong , Chan Lai N. , Müschen Markus , Merchant Akil A. , Lu Rong
Published: November 2021

Cellular heterogeneity is a major cause of treatment resistance in cancer. Despite recent advances in single-cell genomic and transcriptomic sequencing, it remains difficult to relate measured molecular profiles to the cellular activities underlying cancer. Here, we present an integrated experimental system that connects single cell gene expression to heterogeneous cancer cell growth, metastasis, and treatment response. Our system integrates single cell transcriptome profiling with DNA barcode based clonal tracking in patient-derived xenograft models. We show that leukemia cells exhibiting unique gene expression respond to different chemotherapies in distinct but consistent manners across multiple mice. In addition, we uncover a form of leukemia expansion that is spatially confined to the bone marrow of single anatomical sites and driven by cells with distinct gene expression. Our integrated experimental system can interrogate the molecular and cellular basis of the intratumoral heterogeneity underlying disease progression and treatment resistance.
A systematic genome-wide mapping of oncogenic mutation selection during CRISPR-Cas9 genome editing
Authors: Sinha Sanju , Barbosa Karina , Cheng Kuoyuan , Leiserson Mark D. M. , Jain Prashant , Deshpande Anagha , Wilson David M. , Ryan Bríd M. , Luo Ji , Ronai Ze’ev A. , Lee Joo Sang , Deshpande Aniruddha J. , Ruppin Eytan
Published: November 2021

Recent studies have reported that genome editing by CRISPR–Cas9 induces a DNA damage response mediated by p53 in primary cells hampering their growth. This could lead to a selection of cells with pre-existing p53 mutations. In this study, employing an integrated computational and experimental framework, we systematically investigated the possibility of selection of additional cancer driver mutations during CRISPR-Cas9 gene editing. We first confirm the previous findings of the selection for pre-existing p53 mutations by CRISPR-Cas9. We next demonstrate that similar to p53, wildtype KRAS may also hamper the growth of Cas9-edited cells, potentially conferring a selective advantage to pre-existing KRAS-mutant cells. These selective effects are widespread, extending across cell-types and methods of CRISPR-Cas9 delivery and the strength of selection depends on the sgRNA sequence and the gene being edited. The selection for pre-existing p53 or KRAS mutations may confound CRISPR-Cas9 screens in cancer cells and more importantly, calls for monitoring patients undergoing CRISPR-Cas9-based editing for clinical therapeutics for pre-existing p53 and KRAS mutations.
Dissection of the amyloid formation pathway in AL amyloidosis
Authors: Kazman Pamina , Absmeier Ramona M. , Engelhardt Harald , Buchner Johannes
Published: November 2021

In antibody light chain (AL) amyloidosis, overproduced light chain (LC) fragments accumulate as fibrils in organs and tissues of patients. In vitro, AL fibril formation is a slow process, characterized by a pronounced lag phase. The events occurring during this lag phase are largely unknown. We have dissected the lag phase of a patient-derived LC truncation and identified structural transitions that precede fibril formation. The process starts with partial unfolding of the VL domain and the formation of small amounts of dimers. This is a prerequisite for the formation of an ensemble of oligomers, which are the precursors of fibrils. During oligomerization, the hydrophobic core of the LC domain rearranges which leads to changes in solvent accessibility and rigidity. Structural transitions from an anti-parallel to a parallel β-sheet secondary structure occur in the oligomers prior to amyloid formation. Together, our results reveal a rate-limiting multi-step mechanism of structural transitions prior to fibril formation in AL amyloidosis, which offers, in the long run, opportunities for therapeutic intervention.
Acute myeloid leukemia maturation lineage influences residual disease and relapse following differentiation therapy
Authors: Ngo Steven , Oxley Ethan P. , Ghisi Margherita , Garwood Maximilian M. , McKenzie Mark D. , Mitchell Helen L. , Kanellakis Peter , Susanto Olivia , Hickey Michael J. , Perkins Andrew C. , Kile Benjamin T. , Dickins Ross A.
Published: November 2021

Acute myeloid leukemia (AML) is a malignancy of immature progenitor cells. AML differentiation therapies trigger leukemia maturation and can induce remission, but relapse is prevalent and its cellular origin is unclear. Here we describe high resolution analysis of differentiation therapy response and relapse in a mouse AML model. Triggering leukemia differentiation in this model invariably produces two phenotypically distinct mature myeloid lineages in vivo. Leukemia-derived neutrophils dominate the initial wave of leukemia differentiation but clear rapidly and do not contribute to residual disease. In contrast, a therapy-induced population of mature AML-derived eosinophil-like cells persists during remission, often in extramedullary organs. Using genetic approaches we show that restricting therapy-induced leukemia maturation to the short-lived neutrophil lineage markedly reduces relapse rates and can yield cure. These results indicate that relapse can originate from therapy-resistant mature AML cells, and suggest differentiation therapy combined with targeted eradication of mature leukemia-derived lineages may improve disease outcome.
Cutting the costs of coastal protection by integrating vegetation in flood defences
Authors: van Zelst Vincent T. M. , Dijkstra Jasper T. , van Wesenbeeck Bregje K. , Eilander Dirk , Morris Edward P. , Winsemius Hessel C. , Ward Philip J. , de Vries Mindert B.
Published: November 2021

Exposure to coastal flooding is increasing due to growing population and economic activity. These developments go hand-in-hand with a loss and deterioration of ecosystems. Ironically, these ecosystems can play a buffering role in reducing flood hazard. The ability of ecosystems to contribute to reducing coastal flooding has been emphasized in multiple studies. However, the role of ecosystems in hybrid coastal protection (i.e. a combination of ecosystems and levees) has been poorly quantified at a global scale. Here, we evaluate the use of coastal vegetation, mangroves, and marshes fronting levees to reduce global coastal protection costs, by accounting for wave-vegetation interaction.The research is carried out by combining earth observation data and hydrodynamic modelling. We show that incooperating vegetation in hybrid coastal protection results in more sustainable and financially attractive coastal protection strategies. If vegetated foreshore levee systems were established along populated coastlines susceptible to flooding, the required levee crest height could be considerably reduced. This would result in a reduction of 320 (range: 107-961) billion USD2005 Power Purchasing Parity (PPP) in investments, of which 67.5 (range: 22.5- 202) billion USD2005 PPP in urban areas for a 1 in 100-year flood protection level.
Photo-fluorination of nanodiamonds catalyzing oxidative dehydrogenation reaction of ethylbenzene
Authors: Luo Zhishan , Wan Qiang , Yu Zhiyang , Lin Sen , Xie Zailai , Wang Xinchen
Published: November 2021

Styrene is one of the most important industrial monomers and is traditionally synthesized via the dehydrogenation of ethylbenzene. Here, we report a photo-induced fluorination technique to generate an oxidative dehydrogenation catalyst through the controlled grafting of fluorine atoms on nanodiamonds. The obtained catalyst has a fabulous performance with ethylbenzene conversion reaching 70% as well as styrene yields of 63% and selectivity over 90% on a stream of 400 °C, which outperforms other equivalent benchmarks as well as the industrial K−Fe catalysts (with a styrene yield of 50% even at a much higher temperature of ca. 600 °C). Moreover, the yield of styrene remains above 50% after a 500 h test. Experimental characterizations and density functional theory calculations reveal that the fluorine functionalization not only promotes the conversion of sp3 to sp2 carbon to generate graphitic layers but also stimulates and increases the active sites (ketonic C=O). This photo-induced surface fluorination strategy facilitates innovative breakthroughs on the carbocatalysis for the oxidative dehydrogenation of other arenes.
Matched cohort study of germline BRCA mutation carriers with triple negative breast cancer in brightness
Authors: Metzger-Filho Otto , Collier Katharine , Asad Sarah , Ansell Peter J. , Watson Mark , Bae Junu , Cherian Mathew , O’Shaughnessy Joyce , Untch Michael , Rugo Hope S. , Huober Jens B. , Golshan Mehra , Sikov William M. , von Minckwitz Gunter , Rastogi Priya , Li Lang , Cheng Lijun , Maag David , Wolmark Norman , Denkert Carsten , Symmans W. Fraser , Geyer Charles E. , Loibl Sibylle , Stover Daniel G.
Published: November 2021

In the BrighTNess trial, carboplatin added to neoadjuvant chemotherapy (NAC) was associated with increased pathologic complete response (pCR) rates in patients with stage II/III triple-negative breast cancer (TNBC). In this matched cohort study, cases with a germline BRCA1/2 mutation (gBRCA; n = 75) were matched 1:2 with non-gBRCA controls (n = 150) by treatment arm, lymph node status, and age to evaluate pCR rates and association of benefit from platinum/PARP inhibitors with validated RNA expression-based immune, proliferation, and genomic instability scores among gBRCA with the addition of carboplatin ± veliparib to NAC. Among the well-matched cohorts, odds of pCR were not higher in gBRCA cancers who received standard NAC with carboplatin (OR 0.24, 95% CI [0.04-1.24], p = 0.09) or with carboplatin/veliparib (OR 0.44, 95% CI [0.10-1.84], p = 0.26) compared to non-gBRCA cancers. Higher PAM50 proliferation, GeparSixto immune, and CIN70 genomic instability scores were each associated with higher pCR rate in the overall cohort, but not specifically in gBRCA cases. In this study, gBRCA carriers did not have higher odds of pCR than non-gBRCA controls when carboplatin ± veliparib was added to NAC, and showed no significant differences in molecular, immune, chromosomal instability, or proliferation gene expression metrics.
A scheme for simulating multi-level phase change photonics materials
Authors: Wang Yunzheng , Ning Jing , Lu Li , Bosman Michel , Simpson Robert E.
Published: November 2021

Chalcogenide phase change materials (PCMs) have been extensively applied in data storage, and they are now being proposed for high resolution displays, holographic displays, reprogrammable photonics, and all-optical neural networks. These wide-ranging applications all exploit the radical property contrast between the PCMs’ different structural phases, extremely fast switching speed, long-term stability, and low energy consumption. Designing PCM photonic devices requires an accurate model to predict the response of the device during phase transitions. Here, we describe an approach that accurately predicts the microstructure and optical response of phase change materials during laser induced heating. The framework couples the Gillespie Cellular Automata approach for modelling phase transitions with effective medium theory and Fresnel equations. The accuracy of the approach is verified by comparing the PCM’s optical response and microstructure evolution with the results of nanosecond laser switching experiments. We anticipate that this approach to simulating the switching response of PCMs will become an important component for designing and simulating programmable photonics devices. The method is particularly important for predicting the multi-level optical response of PCMs, which is important for all-optical neural networks and PCM-programmable perceptrons.
The draining of capillary liquids from containers with interior corners aboard the ISS
Authors: McCraney Joshua , Weislogel Mark , Steen Paul
Published: November 2021

In this work, we analyze liquid drains from containers in effective zero-g conditions aboard the International Space Station (ISS). The efficient draining of capillary fluids from conduits, containers, and media is critical in particular to high-value liquid samples such as minuscule biofluidics processing on earth and enormous cryogenic fuels management aboard spacecraft. The amount and rate of liquid drained can be of key concern. In the absence of strong gravitational effects, system geometry, and liquid wetting dominate capillary fluidic behavior. During the years 2010–2015, NASA conducted a series of handheld experiments aboard the ISS to observe “large” length scale capillary fluidic phenomena in a variety of irregular containers with interior corners. In this work, we focus on particular single exit port draining flows from such containers and digitize hours of archived NASA video records to quantify transient interface profiles and volumetric flow rates. These data are immediately useful for theoretical and numerical model benchmarks. We demonstrate this by making comparisons to lubrication models for slender flows in simplified geometries which show variable agreement with the data, in part validating certain geometry-dependent dynamical interface curvature boundary conditions while invalidating others. We further compare the data for the draining of complex vane networks and identify the limits of the current theory. All analyzed data is made available to the public as MATLAB files, as detailed within.
Machine learning of high dimensional data on a noisy quantum processor
Authors: Peters Evan , Caldeira João , Ho Alan , Leichenauer Stefan , Mohseni Masoud , Neven Hartmut , Spentzouris Panagiotis , Strain Doug , Perdue Gabriel N.
Published: November 2021

Quantum kernel methods show promise for accelerating data analysis by efficiently learning relationships between input data points that have been encoded into an exponentially large Hilbert space. While this technique has been used successfully in small-scale experiments on synthetic datasets, the practical challenges of scaling to large circuits on noisy hardware have not been thoroughly addressed. Here, we present our findings from experimentally implementing a quantum kernel classifier on real high-dimensional data taken from the domain of cosmology using Google’s universal quantum processor, Sycamore. We construct a circuit ansatz that preserves kernel magnitudes that typically otherwise vanish due to an exponentially growing Hilbert space, and implement error mitigation specific to the task of computing quantum kernels on near-term hardware. Our experiment utilizes 17 qubits to classify uncompressed 67 dimensional data resulting in classification accuracy on a test set that is comparable to noiseless simulation.
Evidence for strong electron correlations in a nonsymmorphic Dirac semimetal
Authors: Hsu Yu-Te , Prishchenko Danil , Berben Maarten , Čulo Matija , Wiedmann Steffen , Hunter Emily C. , Tinnemans Paul , Takayama Tomohiro , Mazurenko Vladimir , Hussey Nigel E. , Perry Robin S.
Published: November 2021

Metallic iridium oxides (iridates) provide a fertile playground to explore new phenomena resulting from the interplay between topological protection, spin-orbit and electron-electron interactions. To date, however, few studies of the low energy electronic excitations exist due to the difficulty in synthesising crystals with sufficiently large carrier mean-free-paths. Here, we report the observation of Shubnikov-de Haas quantum oscillations in high-quality single crystals of monoclinic SrIrO3 in magnetic fields up to 35 T. Analysis of the oscillations reveals a Fermi surface comprising multiple small pockets with effective masses up to 4.5 times larger than the calculated band mass. Ab-initio calculations reveal robust linear band-crossings at the Brillouin zone boundary, due to its non-symmorphic symmetry, and overall we find good agreement between the angular dependence of the oscillations and the theoretical expectations. Further evidence of strong electron correlations is realized through the observation of signatures of non-Fermi liquid transport as well as a large Kadowaki-Woods ratio. These collective findings, coupled with knowledge of the evolution of the electronic state across the Ruddlesden-Popper iridate series, establishes monoclinic SrIrO3 as a topological semimetal on the boundary of the Mott metal-insulator transition.
Economic, environmental and grid-resilience benefits of converting diesel trains to battery-electric
Authors: Popovich Natalie D. , Rajagopal Deepak , Tasar Elif , Phadke Amol
Published: November 2021

Nearly all US locomotives are propelled by diesel-electric drives, which emit 35 million tonnes of CO2 and produce air pollution causing about 1,000 premature deaths annually, accounting for approximately US$6.5 billion in annual health damage costs. Improved battery technology plus access to cheap renewable electricity open the possibility of battery-electric rail. Here we show that a 241-km range can be achieved using a single standard boxcar equipped with a 14-MWh battery and inverter, while consuming half the energy consumed by diesel trains. At near-future battery prices, battery-electric trains can achieve parity with diesel-electric trains if environmental costs are included or if rail companies can access wholesale electricity prices and achieve 40% use of fast-charging infrastructure. Accounting for reduced criteria air pollutants and CO2 emissions, switching to battery-electric propulsion would save the US freight rail sector US$94 billion over 20 years.
Analyzing the delays of target lane vehicles caused by vehicle lane-changing operation
Authors: Yang Quantao , Lu Feng , Ma Jun , Niu Xuejun , Wang Jingsheng
Published: November 2021

Vehicle lane-changing on urban roads is the most common traffic behavior, in which the driver changes the direction or increases the speed of the vehicle by changing its trajectory. However, in high-density traffic flow, when a vehicle changes lanes, a series of vehicles following the target vehicle in the target lane will be delayed. In this study, DJI Phantom 4 drones were used to vertically record the traffic on a road section. Tracker software was then used to extract vehicle information from the video taken by the drones, including the vehicle operating speeds, etc. SPSS 22 and Origin analysis software were then employed to analyze the correlations between different vehicle operating parameters. It was found that the operating speed of the first vehicle following the target vehicle in the target lane is related to the speeds and positions of both the target vehicle and the vehicle preceding it. Under the condition of high-density traffic flow, when the target vehicle is inserted into the target lane, the speed of the vehicles following the target vehicle in the target lane will change. To model this process, the corresponding Sine and DoseResp models were constructed. By calculating the delays of vehicles following the target vehicle in the target lane, it was concluded that the overall delay of the fleet is 3.9–9.5 s.
Decreased resting and nursing in short-finned pilot whales when exposed to louder petrol engine noise of a hybrid whale-watch vessel
Authors: Arranz P. , Glarou M. , Sprogis K. R.
Published: November 2021

Vessel noise is a primary driver of behavioural disturbance in cetaceans, which are targeted during whale-watch activities. Despite the growing, global effort for implementing best-practice principles, to date, there are no regulations on whale-watch vessel noise levels. Here, we test the hypothesis that a whale-watch vessel with a low noise emission will not elicit short-term behavioural responses in toothed whales compared to a vessel with a louder engine. We measured behavioural responses (n = 36) of short-finned pilot whales (Globicephala macrorhynchus) to whale-watch vessel approaches (range 60 m, speed 1.5 kn). Treatment approaches with a quieter electric engine (136–140 dB) compared to the same vessel with a louder petrol engine (151–139 dB) (low-frequency–mid-frequency weighted source levels, re 1 µPa RMS @ 1 m) were examined. Focal whales were resting mother and calves in small group sizes. During petrol engine treatments, the mother’s mean resting time decreased by 29% compared to the control (GLM, p = 0.009). The mean proportion of time nursing for the calf was significantly influenced by petrol engine vessel passes, with a 81% decrease compared to the control (GLM, p = 0.01). There were no significant effects on behaviour from the quieter electric engine. Thus, to minimise disturbance on the activity budget of pilot whales, whale-watch vessels would ideally have source levels as low as possible, below 150 dB re 1 µPa RMS @ 1 m and perceived above ambient noise.
The ‘excess gas’ method for laboratory formation of methane hydrate-bearing sand: geotechnical application
Authors: Rake Lior , Pinkert Shmulik
Published: November 2021

Over recent years, there has been a growing interest in producing methane gas from hydrate-bearing sands (MHBS) located below the permafrost in arctic regions and offshore within continental margins. Geotechnical stability of production wellbores is one of the significant challenges during the gas extraction process. The vast majority of geotechnical investigations of MHBS have been conducted on laboratory-formed samples due to the complex procedure of undisturbed sample extraction. One of the most commonly used hydrate laboratory-formation methods is the excess-gas method. This work investigates fundamental aspects in the excess-gas formation of MHBS that are affecting the geotechnical interpretation and modeling. The work finds that (1) the measured temperature in the experimental system may be quite different from the in-sample temperature, and can reach 4 $$^\circ$$

∘

C difference during thermodynamic processes. This potential difference must be considered in investigation of hydrate formation or dissociation, (2) various calculation approaches may yield different hydrate saturation values of up to tens of percentages difference in high hydrate saturations. The calculation formulas are specified together with the fundamental difference between them, (3) the water mixture method during the sample assembling is critical for homogeneous MHBS laboratory formation, in which a maximum initial water content threshold of 9.1 to 1.3 % are obtained for a minimal fraction size of 0.01 to 0.8 mm, respectively, (4) the hydrate formation duration may influence the MHBS properties, and should be rigorously estimated according to the real-time gas consumption convergence. The outcomes of this work may contribute to the integration of data sets derived from various experiments for the study of MHBS mechanical behavior.
A structured exercise to relieve musculoskeletal pain caused by face-down posture after retinal surgery: a randomized controlled trial
Authors: Kim A-Young , Hwang Sungsoon , Kang Se Woong , Shin So Yeon , Chang Won Hyuk , Kim Sang Jin , Noh Hoon
Published: November 2021

Face-down posture after vitrectomy physically burdens patients. Despite being of significant concern for patients, the intraoperative pain and discomfort has not been of great interest to retinal surgeons or researchers. This randomized controlled trial evaluated the effect of a 3-day novel structured exercise on reducing musculoskeletal pain from the face-down posture in 61 participants (31 in the exercise group) who underwent vitrectomy. Among the subjects, the median age was 62 years, 42 were female, 42 had macular holes, and 19 had retinal detachments. Participants in the exercise group received initial education on the exercise and performed three daily active exercise sessions. After the sessions, the exercise group had median numeric pain scores of 2, 1, and 1 at the back neck, shoulder, and lower back, respectively, while the control group had corresponding scores of 5, 3, and 4, respectively. The exercise group reported significantly lower pain scores (P = .003, .039, and .006 for the back neck, shoulder, and lower back, respectively). Application of the structured exercise would alleviate the patients’ position-induced postoperative physical burden, by reducing pain and discomfort.
Numerical and experimental analysis of a hybrid material acoustophoretic device for manipulation of microparticles
Authors: Barani Alireza , Mosaddegh Peiman , Haghjooy Javanmard Shaghayegh , Sepehrirahnama Shahrokh , Sanati-Nezhad Amir
Published: November 2021

Acoustophoretic microfluidic devices have been developed for accurate, label-free, contactless, and non-invasive manipulation of bioparticles in different biofluids. However, their widespread application is limited due to the need for the use of high quality microchannels made of materials with high specific acoustic impedances relative to the fluid (e.g., silicon or glass with small damping coefficient), manufactured by complex and expensive microfabrication processes. Soft polymers with a lower fabrication cost have been introduced to address the challenges of silicon- or glass-based acoustophoretic microfluidic systems. However, due to their small acoustic impedance, their efficacy for particle manipulation is shown to be limited. Here, we developed a new acoustophoretic microfluid system fabricated by a hybrid sound-hard (aluminum) and sound-soft (polydimethylsiloxane polymer) material. The performance of this hybrid device for manipulation of bead particles and cells was compared to the acoustophoretic devices made of acoustically hard materials. The results show that particles and cells in the hybrid material microchannel travel to a nodal plane with a much smaller energy density than conventional acoustic-hard devices but greater than polymeric microfluidic chips. Against conventional acoustic-hard chips, the nodal line in the hybrid microchannel could be easily tuned to be placed in an off-center position by changing the frequency, effective for particle separation from a host fluid in parallel flow stream models. It is also shown that the hybrid acoustophoretic device deals with smaller temperature rise which is safer for the actuation of bioparticles. This new device eliminates the limitations of each sound-soft and sound-hard materials in terms of cost, adjusting the position of nodal plane, temperature rise, fragility, production cost and disposability, making it desirable for developing the next generation of economically viable acoustophoretic products for ultrasound particle manipulation in bioengineering applications.
The effect of spacers in dual drug-polymer conjugates toward combination therapeutic efficacy
Authors: Xu Juan , Ma Mengdi , Mukerabigwi Jean Felix , Luo Shiying , Zhang Yuannian , Cao Yu , Ning Lifeng
Published: November 2021

Recently, a great effort has been made to perfect the therapeutic effect of solid tumor, from single-agent therapy to combined therapy and many other polymer-drug conjugations with dual or more anticancer agents due to their promising synergistic effect and higher drug level accumulation towards tumor tissues. Different polymer-drug spacers present diverse therapeutic efficacy, therefore, finding an appropriate spacer is desirable. In this study, dual drugs that are doxorubicin (DOX) and mitomycin C (MMC) were conjugated onto a polymer carrier (xyloglucan) via various peptide or amide bonds, and a series of polymers drug conjugates were synthesized with different spacers and their effect on tumor treatment efficacy was studied both in vitro and in vivo. The result shows that the synergistic effect is better when using different linker to conjugate different drugs rather than using the same spacer to conjugate different drugs on the carrier. Particularly, the finding of this works suggested that, using peptide bond for MMC and amide bond for DOX to conjugate dual drugs onto single XG carrier could improve therapeutic effect and synergy effect. Therefore, in polymer-pharmaceutical formulations, the use of different spacers to optimize the design of existing drugs to enhance therapeutic effects is a promising strategy.
Circulating sTweak is associated with visceral adiposity and severity in patients with obstructive sleep apnea syndrome
Authors: Cilekar Sule , Beysel Selvihan , Karatas Savas , Balci Aydin , Akaslan Kursad , Uncu Ali
Published: November 2021

Hypoxia is linked to an inflammatory imbalance in obstructive sleep apnea syndrome (OSAS). Circulating soluble tumor necrosis factor (TNF)-like weak inducer of apoptosis (sTWEAK) is a cytokine that regulates inflammation and insulin resistance in adipose tissue. This study first investigated sTWEAK concentrations in patients OSAS and evaluated associations between sTWEAK concentrations and visceral adiposity, metabolic dysfunction, and hypoxia observed in OSAS. Forty age, sex, and body mass index-matched patients with simple habitual snoring (HSS) and 70 patients with OSAS were included. Patients were divided according to OSAS severity: mild-moderate (apnea–hypopnea index, AHI 5–30 events/h) and severe (AHI ≥ 30 events/h). Anthropometric data, glucose metabolism, visceral fat (VF) ratio, and sTWEAK levels were compared. sTWEAK levels were higher in the OSAS group than in the HSS group (931.23 ± 136.48 vs. 735.22 ± 102.84 ng/L, p = 0.001). sTWEAK levels were higher in severe OSAS than in mild-moderate OSAS (1031.83 ± 146.69 vs. 891.01 ± 110.01 ng/L, p = 0.002. When we evaluated the sTWEAK value and AHI, VF ratio, total cholesterol, blood pressure, homeostasis model of assessment-insulin resistance, and high-sensitivity C-reactive protein using multiple regression analysis, a significant correlation was found between sTWEAK levels and AHI (p < 0.001). It was found that sTWEAK levels were not correlated with glucose metabolism and VF ratio. Increased circulating sTWEAK levels were associated with the severity of OSAS. High sTWEAK levels were correlated with increased AHI. sTWEAK concentrations are linked to severe OSAS.
Lightning-induced high temperature and pressure microstructures in surface and subsurface fulgurites
Authors: Kuo Li-Wei , Smith Steven A. F. , Chen Chien-Chih , Ku Ching-Shun , Chiang Ching-Yu , Brown Dennis , Negrini Marianne , Huang Wen-Jeng , Chen Tze-Yuan
Published: November 2021

Cloud-to-ground lightning causes both high-temperature and high-pressure metamorphism of rocks, forming rock fulgurite. We demonstrate that a range of microstructural features indicative of high temperatures and pressures can form in fulgurites at the surface and in fractures up to several meters below the surface. In comparison to a granite reference sample collected from a borehole at a depth of 138 m, microstructures in both the surface and fracture fulgurite are characterized by: (i) the presence of glass, (ii) a phase transformation in K-feldspar with the presence of exsolution lamellae of plagioclase, and (iii) high residual stresses up to 1.5 GPa. Since this is the first time that fracture-related fulgurite has been described, we also carried out a 1-D numerical model to investigate the processes by which these can form. The model shows that the electric current density in fractures up to 40 m from the landing point can be as high as that on the surface, providing an explanation for the occurrence of fracture-related fulgurites. Our work broadens the near-surface environments in which rock fulgurite has been reported, and provides a detailed description of microstructures that can be compared to those formed during other types of extreme metamorphic events.
Triphase contrast-enhanced CT to evaluate indications for autologous liver transplantation in patients with end-stage hepatic alveolar echinococcosis
Authors: Chen Jing , Wei Li , Chen Tian-Wu , Li Rui , Zhang Xiao-Ming , Deng Chun-Mei , Zhang Yi , Xiong Jing , Li Xian-Zhong , Li Zhi-Hong
Published: November 2021

Autologous liver transplantation (ALT) to cure end-stage hepatic alveolar echinococcosis (HAE) requires that hepatobiliary surgeons understand the invasion of intrahepatic structure and adjacent tissues or organs. Triphase contrast-enhanced CT of the liver has been widely used for diagnosis and preoperative evaluation of HAE. Three-dimensional (3D) reconstruction allows for accurate measurement of remnant liver volume (RLV). The objective of the study was to evaluate value of triphase contrast-enhanced CT together with 3D reconstruction in preoperative evaluation of indications for ALT in patients with end-stage HAE. This cohort include twenty-one consecutive patients with end-stage HAE, who preoperatively underwent triphase enhanced CT together with 3D reconstruction for ALT. To depict the indications, the 2D image data were reviewed statistically focusing on porta hepatis invasion, retrohepatic vena cava (RHVC) involvement and degrees of intrahepatic vessel invasion, and the 3D reconstruction was performed to obtain ratio of RLV to standard liver volume (SLV). The results showed that 95.24% patients (20/21) had porta hepatis invasion. When lesions located in right liver lobe, porta hepatis invasion occurred most commonly in the second and third porta hepatis (7/10), whereas the first, second and third porta hepatis were most commonly invaded by lesions in the right and caudate / left medial liver lobes (7/11) (P < 0.05). The mean value of longitudinal invasion of RHVC was 8.0 cm, and 95.2% (20/21) of patients had RHVC invasion with ≥ 180° circumferential invasion. As for the important vascular events, moderate and severe invasion occurred most commonly in the right hepatic vein, right branch of portal vein and RHVC each in 95.2% (20/21) patients (P < 0.05). We also found that preoperative CT had a good agreement with intraoperative findings in assessing intrahepatic vascular involvement by HAE (kappa index = 0.77). The estimated average ratio of RLV to SLV was 0.95 (range, 0.43–1.62). In conclusion, the 2D contrast-enhanced CT could well depict anatomic location and size of HAE, and invasion of porta hepatis and vascular by this disease, and involvement of other adjacent organs and tissues. Above all, 3D reconstruction could accurately measure RLV in patients with end-stage HAE for ALT.
Modeling Eastern Russian High Arctic Geese (Anser fabalis, A. albifrons) during moult and brood rearing in the ‘New Digital Arctic’
Authors: Solovyeva Diana , Bysykatova-Harmey Inga , Vartanyan Sergey L. , Kondratyev Alexander , Huettmann Falk
Published: November 2021

Many polar species and habitats are now affected by man-made global climate change and underlying infrastructure. These anthropogenic forces have resulted in clear implications and many significant changes in the arctic, leading to the emergence of new climate, habitats and other issues including digital online infrastructure representing a ‘New Artic’. Arctic grazers, like Eastern Russian migratory populations of Tundra Bean Goose Anser fabalis and Greater White-fronted Goose A. albifrons, are representative examples and they are affected along the entire flyway in East Asia, namely China, Japan and Korea. Here we present the best publicly-available long-term (24 years) digitized geographic information system (GIS) data for the breeding study area (East Yakutia and Chukotka) and its habitats with ISO-compliant metadata. Further, we used seven publicly available compiled Open Access GIS predictor layers to predict the distribution for these two species within the tundra habitats. Using BIG DATA we are able to improve on the ecological niche prediction inference for both species by focusing for the first time specifically on biological relevant population cohorts: post-breeding moulting non-breeders, as well as post-breeding parent birds with broods. To assure inference with certainty, we assessed it with 4 lines of evidence including alternative best-available open access field data from GBIF.org as well as occurrence data compiled from the literature. Despite incomplete data, we found a good model accuracy in support of our evidence for a robust inference of the species distributions. Our predictions indicate a strong publicly best-available relative index of occurrence (RIO). These results are based on the quantified ecological niche showing more realistic gradual occurrence patterns but which are not fully in agreement with the current strictly applied parsimonious flyway and species delineations. While our predictions are to be improved further, e.g. when synergetic data are made freely available, here we offer within data caveats the first open access model platform for fine-tuning and future predictions for this otherwise poorly represented region in times of a rapid changing industrialized ‘New Arctic’ with global repercussions.
Green extraction optimization of triterpenoid glycoside-enriched extract from Centella asiatica (L.) Urban using response surface methodology (RSM)
Authors: Thong-on Wachiraporn , Pathomwichaiwat Thanika , Boonsith Suthida , Koo-amornpattana Wanida , Prathanturarug Sompop
Published: November 2021

Centella asiatica (L.) Urban extracts are widely used as food, drugs and cosmetics, and the main active compounds are glycosides (madecassoside and asiaticoside) and aglycones (madecassic acid and asiatic acid). Green extraction is an interesting concept that can produce safe and high-quality extracts that use less solvent, time and energy with the environmental friendly. This study investigated the optimum conditions for extracting a triterpenoid glycoside-enriched C. asiatica extract using microwave-assisted extraction (MAE) and ultrasound-assisted extraction (UAE). Central composite design and response surface methodology (RSM) were used for the experimental design and data analysis. Four-month-old C. asiatica tetraploid plants were selected as the elite raw material containing high amount of triterpenoid glycosides for the extraction experiments, and the triterpenoid content was determined by a validated HPLC method. The results demonstrated that the RSM models and equations were reliable and could predict the optimal conditions to enhance C. asiatica extract yield, glycoside and aglycone amounts. The percent of ethanol was the major factor that had a significant effect on C. asiatica yield and glycoside and aglycone content during MAE and UAE. The maximum triterpenoids content in extract; 7.332 ± 0.386% w/w madecassoside and 4.560 ± 0.153% w/w asiaticoside 0.357 ± 0.013% w/w madecassic acid and 0.209 ± 0.025% w/w asiatic acid were obtained by MAE with 80% ethanol at 100 watts for 7.5 min, whereas the optimal conditions for highest total triterpenoids extraction from dry plant was UAE with 80% ethanol, temperature 48 °C, 50 min enhanced 2.262 ± 0.046% w/w madecassoside, 1.325 ± 0.062% w/w asiaticoside, 0.082 ± 0.009% w/w madecassic acid and 0.052 ± 0.007% w/w asiatic acid as secondary outcome. Moreover, it was found that MAE and UAE consumed energy 59 and 54%, respectively, lower than that of the conventional method, maceration, in term of kilowatt-hour per gram of total triterpenoids. These optimized green conditions could be recommended for C. asiatica extraction for triterpenoid glycoside-enriched extracts production for the pharmaceutical or cosmeceutical industries and triterpenoids quantitative analysis in raw materials.