bluuebunny/crossref_metadata_2025 huggingface dataset:
Local-scale phase velocity estimation using ambient seismic noise: comparison between passive seismic interferometry and conventional frequency–wavenumber methods
Authors: Karaaslan Aylin , Kocaoğlu Argun , Özalaybey Serdar
Published: February 2021

We present a new processing scheme that uses passive seismic interferometry (PSI) followed by multichannel analysis of surface waves (MASW), which we call the 2-D PSI-MASW method, to obtain Rayleigh wave phase velocity dispersion (PVD) information. In this scheme, we first use the principles of PSI to form multidirectional cross-correlations (CCs) then project the CCs onto a 1-D virtual array and apply the phase-shift transform as in MASW processing. We compare PVD information obtained by this method with those of the conventional beam-power based frequency–wavenumber decomposition (CVFK) method using ambient seismic noise (ASN) data collected by local-scale 2-D arrays deployed at three selected sites in Bursa, Turkey. By analysing the ASN data from these sites, we show that similar multimodal PVD curves can be obtained with the two methods over a broad frequency range (∼2–23 Hz) within the wavenumber resolution and aliasing limits. However, in one of our sites where the 2-D array configuration has a considerable antisymmetry, we show that the 1-D virtual array used in the 2-D PSI-MASW method has a better array response function in terms of wavenumber resolution and suppression of side-lobes leading to superior mode resolution and separation than that of the CVFK method, which shows strong directional variations. Furthermore, unlike the CVFK method, the 2-D PSI-MASW method takes advantage of temporal stacking of CCs ensuring weak but coherent Rayleigh wave signals present in the ASN wavefield to be strengthened and has the potential for better extraction of PVD information. We conclude that by using a 2-D array with spatial coverage providing a wide range of directions and distances, reliable PVD information can be obtained even if the ASN sources are not concentrated in the stationary phase zones. Thus, we suggest that the 2-D PSI-MASW method is highly advantageous for the extraction of reliable PVD information owing to the multidirectional CCs provided by the 2-D array configurations. We also report that using only a single receiver line in the interferometric approach results in biased and/or incomplete PVD information due to the non-isotropic ASN source distribution at all three sites we analysed. In conclusion, our results clearly indicate that the 2-D PSI-MASW method can be used as complementary or alternative to the CVFK method to extract multimodal Rayleigh wave PVD information in local-scale seismological studies.
Nanopore direct RNA sequencing detects DUX4-activated repeats and isoforms in human muscle cells
Authors: Mitsuhashi Satomi , Nakagawa So , Sasaki-Honda Mitsuru , Sakurai Hidetoshi , Frith Martin C , Mitsuhashi Hiroaki
Published: February 2021

Facioscapulohumeral muscular dystrophy (FSHD) is an inherited muscle disease caused by misexpression of the DUX4 gene in skeletal muscle. DUX4 is a transcription factor, which is normally expressed in the cleavage-stage embryo and regulates gene expression involved in early embryonic development. Recent studies revealed that DUX4 also activates the transcription of repetitive elements such as endogenous retroviruses (ERVs), mammalian apparent long terminal repeat (LTR)-retrotransposons and pericentromeric satellite repeats (Human Satellite II). DUX4-bound ERV sequences also create alternative promoters for genes or long non-coding RNAs, producing fusion transcripts. To further understand transcriptional regulation by DUX4, we performed nanopore long-read direct RNA sequencing (dRNA-seq) of human muscle cells induced by DUX4, because long reads show whole isoforms with greater confidence. We successfully detected differential expression of known DUX4-induced genes and discovered 61 differentially expressed repeat loci, which are near DUX4–ChIP peaks. We also identified 247 gene–ERV fusion transcripts, of which 216 were not reported previously. In addition, long-read dRNA-seq clearly shows that RNA splicing is a common event in DUX4-activated ERV transcripts. Long-read analysis showed non-LTR transposons including Alu elements are also transcribed from LTRs. Our findings revealed further complexity of DUX4-induced ERV transcripts. This catalogue of DUX4-activated repetitive elements may provide useful information to elucidate the pathology of FSHD. Also, our results indicate that nanopore dRNA-seq has complementary strengths to conventional short-read complementary DNA sequencing.
Fish without Tail Fins—Exploring the Function of Tail Morphology of the First Vertebrates
Authors: Rival David E , Yang Wenchao , Caron Jean-Bernard
Published: February 2021

Synopsis

We use a series of hydrodynamic experiments on abstracted models to explore whether primitive vertebrates may have swum under various conditions without a clearly-differentiated tail fin. Cambrian vertebrates had post-anal stubby tails, some had single dorsal and ventral fins, but none had yet evolved a clearly differentiated caudal fin typical of post-Cambrian fishes, and must have relied on their long and flexible laterally-compressed bodies for locomotion, i.e., by bending their bodies side-to-side in order to propagate waves from head to tail. We approach this problem experimentally based on an abstracted model of Metaspriggina walcotti from the 506-million-year old Burgess Shale by using oscillating thin flexible plates while varying the tail fin geometry from rectangular to uniform, and finally to a no tail–fin condition. Despite a missing tail fin, this study supports the observation that the abstracted Metaspriggina model can generate a strong propulsive force in cruise conditions, both away from, and near the sea bed (in ground effect). However, when the abstracted Metaspriggina model moves in ground effect, a weaker performance is observed, indicating that Metaspriggina may not necessarily have been optimized for swimming near the sea bed. When considering acceleration from rest, we find that the Metaspriggina model's performance is not significantly different from other morphological models (abstracted truncate tail and abstracted heterocercal tail). Statistical analysis shows that morphological parameters, swimming modes, and ground effect all play significant roles in thrust performance. While the exact relationships of Cambrian vertebrates are still debated, as agnathans, they share some general characteristics with modern cyclostomes, in particular an elongate body akin to lampreys. Lampreys, as anguilliform swimmers, are considered to be some of the most efficient swimmers using a particular type of suction thrust induced by the traveling body wave as it travels from head to tail. Our current experiments suggest that Metaspriggina’s ability in acceleration from rest, through possibly a similar type of suction thrust, which is defined as the ability to generate low pressure on upstream facing sections of the body, might have evolved early in response to increasing predator pressure during the Cambrian Explosion.
Measuring Self-Reported Cancer-Related Cognitive Impairment: Recommendations From the Cancer Neuroscience Initiative Working Group
Authors: Henneghan Ashley M , Van Dyk Kathleen , Kaufmann Tara , Harrison Rebecca , Gibbons Christopher , Heijnen Cobi , Kesler Shelli R
Published: February 2021

Cancer and its treatments are associated with increased risk for cancer-related cognitive impairment (CRCI). Methods and measures used to study and assess self-reported CRCI (sr-CRCI), however, remain diverse, resulting in heterogeneity across studies. The Patient-Reported Outcomes Working Group has been formed to promote homogeneity in the methods used to study sr-CRCI. In this report, using a psychometric taxonomy, we inventory and appraise instruments used in research to measure sr-CRCI, and we consider advances in patient-reported outcome methodology. Given its psychometric properties, we recommend the Patient-Reported Outcome Measurement Information System Cognitive Function Short Form 8a for measurement of sr-CRCI in cancer patients and survivors, at a minimum, to increase scientific rigor and progress in addressing CRCI.
Single-cell mapper (scMappR): using scRNA-seq to infer the cell-type specificities of differentially expressed genes
Authors: Sokolowski Dustin J , Faykoo-Martinez Mariela , Erdman Lauren , Hou Huayun , Chan Cadia , Zhu Helen , Holmes Melissa M , Goldenberg Anna , Wilson Michael D
Published: February 2021

RNA sequencing (RNA-seq) is widely used to identify differentially expressed genes (DEGs) and reveal biological mechanisms underlying complex biological processes. RNA-seq is often performed on heterogeneous samples and the resulting DEGs do not necessarily indicate the cell-types where the differential expression occurred. While single-cell RNA-seq (scRNA-seq) methods solve this problem, technical and cost constraints currently limit its widespread use. Here we present single cell Mapper (scMappR), a method that assigns cell-type specificity scores to DEGs obtained from bulk RNA-seq by leveraging cell-type expression data generated by scRNA-seq and existing deconvolution methods. After evaluating scMappR with simulated RNA-seq data and benchmarking scMappR using RNA-seq data obtained from sorted blood cells, we asked if scMappR could reveal known cell-type specific changes that occur during kidney regeneration. scMappR appropriately assigned DEGs to cell-types involved in kidney regeneration, including a relatively small population of immune cells. While scMappR can work with user-supplied scRNA-seq data, we curated scRNA-seq expression matrices for ∼100 human and mouse tissues to facilitate its stand-alone use with bulk RNA-seq data from these species. Overall, scMappR is a user-friendly R package that complements traditional differential gene expression analysis of bulk RNA-seq data.
Leptospirosis Followed by Kawasaki-Like Disease: Case Report From an Adult Swiss Patient and Review of the Literature
Authors: Baerlocher Severin , Helfenstein Seth , Mahr Alfred , Crippa Selina , Garcia Boy Regine , Kahlert Christian R , Yurttas Timur , Hatz Christoph , Kohler Philipp
Published: February 2021

Kawasaki disease (KD) is a vasculitis that mostly occurs in children, but rare cases in adults have been reported. We describe the case of a 43-year-old Swiss male who developed symptoms compatible with KD 7 weeks after leptospirosis, which was presumably acquired after swimming in a creek in the Swiss Alps. We performed a literature review and identified 10 other cases (all in children), in which Kawasaki-like disease was diagnosed in the context of leptospirosis. Outcome was favourable in most cases, including our patient. This exceptional case demonstrates both the possibility of autochthonous cases of leptospirosis in Switzerland as well as a possible association of leptospirosis with Kawasaki-like disease.
ClearSeeAlpha: Advanced Optical Clearing for Whole-Plant Imaging
Authors: Kurihara Daisuke , Mizuta Yoko , Nagahara Shiori , Higashiyama Tetsuya
Published: February 2021

To understand how the body of plants is made, it is essential to observe the morphology, structure and arrangement of constituent cells. However, the opaque nature of the plant body makes it difficult to observe the internal structures directly under a microscope. To overcome this problem, we developed a reagent, ClearSee, that makes plants transparent, allowing direct observation of the inside of a plant body without inflicting damage on it, e.g. through physical cutting. However, because ClearSee is not effective in making some plant species and tissues transparent, in this study, we further improved its composition to prevent oxidation, and have developed ClearSeeAlpha, which can be applied to a broader range of plant species and tissues. Sodium sulfite, one of the reductants, prevented brown pigmentation due to oxidation during clearing treatment. Using ClearSeeAlpha, we show that it is possible to obtain clear chrysanthemum leaves, tobacco and Torenia pistils and fertilized Arabidopsis thaliana fruits—tissues that have hitherto been challenging to clear. Moreover, we show that the fluorescence intensity of purified fluorescent proteins emitting light of various colors was unaffected in the ClearSeeAlpha solution; only the fluorescence intensity of TagRFP was reduced by about half. ClearSeeAlpha should be useful in the discovery and analysis of biological phenomena occurring deep inside the plant tissues.
Measurement Properties of Outcome Measures Used to Assess Physical Impairments in Patients After Distal Radius Fracture: A Systematic Review
Authors: Ziebart Christina , Mehta Saurabh P , MacDermid Joy
Published: February 2021

Objectives

Individuals with distal radius fractures (DRF) may experience difficulty with gripping an object, painful wrist movements, sensorimotor difficulties, and swelling around the wrist and hand. A comprehensive review of the existing evidence concerning the measurement properties of common physical impairment measures can provide a valuable resource to guide hand therapy practice while managing DRF. The primary objective was to locate and assess the quality of literature on the measurement properties for the measures of physical impairment used in individuals with DRF.

Methods

Two reviewers searched PubMed, CINAHL, and EMBASE. A combination of DRF, measurement properties, and physical impairments were used as keywords, and articles were independently assessed using the Consensus-Based Standards for the Selection of Health Measurement Instruments critical appraisal tool. Primary studies were included if they examined at least 1 of the following: reliability, validity, responsiveness, or indices of true and meaningful changes for measures of physical impairment in the DRF sample. A total of 19 articles were included in this review. The quality of the studies ranged from 46% to 92%. This review suggests that measures such as assessment of grip strength and supination and pronation range of motion (ROM), using various goniometric devices, showed good intrarater and interrater reliability, construct validity, and responsiveness in individuals with DRF.

Conclusion

Acceptable reliability and responsiveness were reported in grip and wrist ROM assessments for measuring changes in wrist and hand function after DRF; however, wrist ROM assessed using traditional goniometric techniques were less reliable in individuals with DRF.

Impact

This study provides insight into which objective tools might be better suited for measuring outcomes related to DRF.
CAP measures towards environmental sustainability—Trade opportunities for Africa?
Authors: Latka Catharina , Heckelei Thomas , Kuhn Arnim , Witzke Heinz-Peter , Kornher Lukas
Published: February 2021

Environmental sustainability is a core aspect of the proposed future EU Common Agricultural Policy (CAP). Policy changes must not compromise socioeconomic development in low-income countries, whereas the extensification of EU agriculture may also create trade opportunities abroad. We apply a global agricultural-economic model to assess EU–African trade-related impacts of potential, environmentally motivated CAP changes. Restrictions on livestock density and nitrogen application reveal reduced EU production levels of meat. This lowers the EU's agricultural environmental burden and share in agricultural trade flows to Africa. However, overall food supply in Africa is not projected to deteriorate substantially, as imports from other world regions and increasing domestic production fill the gap. While this weakens the global emission reduction potential, net livestock producers in Africa may benefit from increasing producer prices. How far potentials for domestic production and trade can be used in African regions depends at least partly on their competitiveness vis-á-vis substituting importers.
The circadian clock: a central mediator of cartilage maintenance and osteoarthritis development?
Authors: Poulsen Raewyn C , Hearn James I , Dalbeth Nicola
Published: February 2021

The circadian clock is a specialized cell signalling pathway present in all cells. Loss of clock function leads to tissue degeneration and premature ageing in animal models demonstrating the fundamental importance of clocks for cell, tissue and organism health. There is now considerable evidence that the chondrocyte circadian clock is altered in OA. The purpose of this review is to summarize current knowledge regarding the nature of the change in the chondrocyte clock in OA and the implications of this change for disease development. Expression of the core clock component, BMAL1, has consistently been shown to be lower in OA chondrocytes. This may contribute to changes in chondrocyte differentiation and extracellular matrix turnover in disease. Circadian clocks are highly responsive to environmental factors. Mechanical loading, diet, inflammation and oxidative insult can all influence clock function. These factors may contribute to causing the change in the chondrocyte clock in OA.
von Willebrand Factor Multimer Formation Contributes to Immunothrombosis in Coronavirus Disease 2019
Authors: Doevelaar Adrian A. N. , Bachmann Martin , Hölzer Bodo , Seibert Felix S. , Rohn Benjamin J. , Bauer Frederic , Witzke Oliver , Dittmer Ulf , Bachmann Michael , Yilmaz Serap , Dittmer Rita , Schneppenheim Sonja , Babel Nina , Budde Ulrich , Westhoff Timm H.
Published: February 2021

OBJECTIVES:

Prevention and therapy of immunothrombosis remain crucial challenges in the management of coronavirus disease 2019, since the underlying mechanisms are incompletely understood. We hypothesized that endothelial damage may lead to substantially increased concentrations of von Willebrand factor with subsequent relative deficiency of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13).

DESIGN:

Prospective controlled cross-over trial.

SETTING:

Blood samples of patients with confirmed coronavirus disease 2019 and healthy controls were obtained in three German hospitals and analyzed in a German hemostaseologic laboratory.

PATIENTS:

Seventy-five patients with confirmed coronavirus disease 2019 of mild to critical severity and 30 healthy controls.

MEASUREMENTS AND MAIN RESULTS:

von Willebrand factor antigen, ADAMTS13, and von Willebrand factor multimer formation were analyzed. von Willebrand factor antigen was 4.1 times higher in COVID-19 patients compared with healthy controls (p < 0.0001), whereas ADAMTS13 activities were not significantly different (p = 0.18). The ADAMTS13/von Willebrand factor antigen ratio was significantly lower in COVID-19 than in the control group (24.4 ± 20.5 vs 82.0 ± 30.7; p < 0.0001). Fourteen patients (18.7%) undercut a critical ratio of 10 as described in thrombotic thrombocytopenic purpura. Gel analysis of multimers resembled a thrombotic thrombocytopenic purpura pattern with loss of the largest multimers in 75% and a smeary triplet pattern in 39% of the patients. The ADAMTS13/von Willebrand factor antigen ratio decreased continuously from mild to critical disease (analysis of variance p = 0.026). Furthermore, it differed significantly between surviving patients and those who died from COVID-19 (p = 0.001) yielding an area under the curve of 0.232 in receiver operating characteristic curve curve analysis.

Conclusion:

COVID-19 is associated with a substantial increase in von Willebrand factor levels, which can exceed the ADAMTS13 processing capacity resulting in the formation of large von Willebrand factor multimers indistinguishable from thrombotic thrombocytopenic purpura. The ADAMTS13/von Willebrand factor antigen ratio is an independent predictor of severity of disease and mortality. These findings provide a rationale to consider plasma exchange as a therapeutic option in COVID-19 and to include von Willebrand factor and ADAMTS13 in the diagnostic workup.
Prone Positioning and Survival in Mechanically Ventilated Patients With Coronavirus Disease 2019–Related Respiratory Failure*
Authors: Mathews Kusum S. , Soh Howard , Shaefi Shahzad , Wang Wei , Bose Sonali , Coca Steven , Gupta Shruti , Hayek Salim S. , Srivastava Anand , Brenner Samantha K. , Radbel Jared , Green Adam , Sutherland Anne , Leonberg-Yoo Amanda , Shehata Alexandre , Schenck Edward J. , Short Samuel A.P. , Hernán Miguel A. , Chan Lili , Leaf David E.
Published: February 2021

OBJECTIVES:

Therapies for patients with respiratory failure from coronavirus disease 2019 are urgently needed. Early implementation of prone positioning ventilation improves survival in patients with acute respiratory distress syndrome, but studies examining the effect of proning on survival in patients with coronavirus disease 2019 are lacking. Our objective was to estimate the effect of early proning initiation on survival in patients with coronavirus disease 2019–associated respiratory failure.

DESIGN:

Data were derived from the Study of the Treatment and Outcomes in Critically Ill Patients with coronavirus disease 2019, a multicenter cohort study of critically ill adults with coronavirus disease 2019 admitted to 68 U.S. hospitals. Using these data, we emulated a target trial of prone positioning ventilation by categorizing mechanically ventilated hypoxemic (ratio of Pao
2 over the corresponding Fio
2 ≤ 200 mm Hg) patients as having been initiated on proning or not within 2 days of ICU admission. We fit an inverse probability–weighted Cox model to estimate the mortality hazard ratio for early proning versus no early proning. Patients were followed until death, hospital discharge, or end of follow-up.

SETTING:

ICUs at 68 U.S. sites

PATIENTS:

Critically ill adults with laboratory-confirmed coronavirus disease 2019 receiving invasive mechanical ventilation with ratio of Pao
2 over the corresponding Fio
2 less than or equal to 200 mm Hg.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Among 2,338 eligible patients, 702 (30.0%) were proned within the first 2 days of ICU admission. After inverse probability weighting, baseline and severity of illness characteristics were well-balanced between groups. A total of 1,017 (43.5%) of the 2,338 patients were discharged alive, 1,101 (47.1%) died, and 220 (9.4%) were still hospitalized at last follow-up. Patients proned within the first 2 days of ICU admission had a lower adjusted risk of death compared with nonproned patients (hazard ratio, 0.84; 95% CI, 0.73–0.97).

CONCLUSIONS:

In-hospital mortality was lower in mechanically ventilated hypoxemic patients with coronavirus disease 2019 treated with early proning compared with patients whose treatment did not include early proning.
Bacterial growth and recovery on hospital biometric devices: effect of two types of disinfectants
Authors: Norton Pedro , Guimarães João Tiago , Pinho Paulo , Ribeiro Manuela , Martins Natália , Mendes Carlos Pedro
Published: February 2021

Objectives:

The aim of the study was to evaluate the presence of bacterial contamination on biometric identification devices in a public hospital; identify the species of bacteria implicated in the contamination and assess bacterial recovery after the use of 2 types of disinfectants: alcohol 70% and isopropyl alcohol chlorhexidine.

Design:

Before and after trial.

Setting:

Public hospital, tertiary referral center.

Participants:

All existing biometric identification devices in the hospital (n = 20).

Methods:

Collection of 2 microbiological samples from the fingerprint reading surface of biometric devices immediately before and after applying the solution with alcohol 70% and in separate time periods with isopropyl alcohol chlorhexidine.

Results:

It have been identified 21 different bacterial species in a total of 78 samples, mostly Staphylococcus epidermidis (32 samples) and S aureus (7 samples). S epidermidis was eliminated in 61.5% of the samples after disinfecting with alcohol 70% and in 92.3% of the samples disinfected with isopropyl alcohol chlorhexidine. S aureus was eliminated in 33.3% and 100% of the samples, respectively. We found no bacterial growth in 10% of the devices after disinfection with 70% alcohol and in 78.9% of devices after disinfection with isopropyl alcohol chlorhexidine. We also found that there was a decrease in the frequency of species isolated after using both disinfection solutions, although isopropyl alcohol chlorhexidine appeared to be more effective.

Conclusions:

The biometric identification devices used in this hospital seem to be safe regardless of the products used for its cleaning. The majority of the bacteria found are commensal skin microorganisms. We did not find pathogenic bacteria for immunocompetent individuals, in particular methicillin-resistant S aureus.
Rare popliteal mass following retrograde nailing of ballistic femur fracture: a case report
Authors: Court Tannor , Gusho Charles A. , Graf Alexander , Schmeling Gregory
Published: February 2021

Introduction:

Civilian ballistic injuries are commonly associated with fracture, vascular injury, and soft tissue trauma. Posttraumatic pseudoaneurysms represent an extremely rare subset of vascular injuries following ballistic fractures.

Case:

We present the rare case of a posttraumatic pseudoaneurysm that occurred after retrograde femoral nailing of a ballistic distal femur fracture. The patient presented in clinic postoperatively with a pulsatile popliteal mass. Distal pulses were intact but subsequent ultrasound and angiography revealed a pseudoaneurysm of the distal superficial femoral artery. The pseudoaneurysm was subsequently treated with a covered stent and the patient's recovery was uncomplicated.

Conclusion:

Due to the potential life and limb-threating complications from pseudoaneurysm rupture, this case report emphasizes the early recognition and expeditious management of vascular complications following ballistic fractures in the civilian population.
Low CD4+ cell count nadir exacerbates the impacts of APOE ε4 on functional connectivity and memory in adults with HIV
Authors: Yang Fan Nils , Bronshteyn Margarita , Flowers Sarah A. , Dawson Matthew , Kumar Princy , Rebeck George William , Turner Raymond Scott , Moore David J. , Ellis Ronald J. , Jiang Xiong
Published: February 2021

Objective:

Nearly half of individuals living with HIV in the USA are now 50 or older. This rapidly ageing populace may be at an increasingly greater risk of Alzheimer's disease. However, the potential interaction between HIV-disease and Alzheimer's disease pathogenesis (i.e. Alzheimer's disease genetic risk factors) on brain function remains an open question. The present study aimed to investigate the impact of APOE ε4 on brain function in middle-aged to older people with HIV (PWH), as well as the putative interaction between ε4 and HIV disease severity.

Methods:

Ninety-nine PWH participated in a cross-sectional study (56.3 ± 6.5 years, range 41–70 years, 27 women, 26 ε4 carriers and 73 noncarriers). Structural MRI and resting-state functional MRI were collected to assess alterations in brain structure and functional connectivity, respectively.

Results:

APOE ε4 was associated with worse memory performance and reduced functional connectivity in the memory network. The functional connectivity reduction was centred at the caudate nucleus rather than hippocampus and correlated with worse memory performance. In ε4 carriers, low CD4+ cell count nadir was associated with reduced functional connectivity in the memory network, but this association was absent in noncarriers. Furthermore, there was an indirect detrimental impact of ε4 on memory performance through memory network functional connectivity. However, this indirect effect was contingent on CD4+ cell count nadir, that is the indirect effect of ε4 on memory was only significant when CD4+ cell count nadir was low.

Interpretation:

APOE ε4 is associated with reduced memory and reduced functional connectivity within the memory network, and low CD4+ cell count nadir -- indicating a history of severe immunosuppression -- may exacerbate the effects of ε4.
Evaluating Spatial Associations in Inpatient Deaths Between Organ Procurement Organizations
Authors: Adler Joel T. , Dey Tanujit
Published: February 2021

Background.

To improve the measurement of organ procurement organization (OPO) performance, the Center for Medicare and Medicaid Services recently proposed using inpatient deaths defined as the eligible pool of organ donors within an OPO as patients 75 years or younger that died from any cause that would not preclude donation.

Methods.

To account for the geographic variation in OPO performance and organ availability across the United States, we utilized spatial analysis to appraise the newly proposed metric of inpatient deaths.

Results.

Using spatial clustering that accounts for geographic relationships between Organ Procurement Organizations, the top 5 causes of donation-eligible death, and inpatient deaths, we identified 4 unique OPO clusters. Each group had a distinct demographic composition, cause of death, and inpatient death pattern. In multivariate analysis accounting for these geographic relationships, the spatial clusters remained significantly associated with the outcome of inpatient deaths (P < 0.001) and were the best-fitting model compared with models without the spatial clusters; this suggests that further risk adjustment of inpatient deaths should include these geographic considerations.

Conclusions.

This approach provides not only a manner to assess donor potential by improving risk adjustment but also an opportunity to further explore geographic and spatial relationships in the practice of organ transplantation and OPO performance.
Solid Organ Transplantation During COVID-19 Pandemic: An International Web-based Survey on Resources’ Allocation
Authors: Giovinazzo Francesco , Avolio Alfonso W. , Galiandro Federica , Vitale Alessandro , Dalla Riva Giulio V. , Biancofiore Gianni , Sharma Shivani , Muiesan Paolo , Agnes Salvatore , Burra Patrizia
Published: February 2021

Background.

Solid organ transplants (SOTs) are life-saving interventions, recently challenged by coronavirus disease 2019 (COVID-19). SOTs require a multistep process, which can be affected by COVID-19 at several phases.

Methods.

SOT-specialists, COVID-19-specialists, and medical ethicists designed an international survey according to CHERRIES guidelines. Personal opinions about continuing SOTs, safe managing of donors and recipients, as well as equity of resources’ allocation were investigated. The survey was sent by e-mail. Multiple approaches were used (corresponding authors from Scopus, websites of scientific societies, COVID-19 webinars). After the descriptive analysis, univariate and multivariate ordinal regression analysis was performed.

Results.

There were 1819 complete answers from 71 countries. The response rate was 49%. Data were stratified according to region, macrospecialty, and organ of interest. Answers were analyzed using univariate-multivariate ordinal regression analysis and thematic analysis. Overall, 20% of the responders thought SOTs should not stop (continue transplant without restriction); over 70% suggested SOTs should selectively stop, and almost 10% indicated they should completely stop. Furthermore, 82% agreed to shift resources from transplant to COVID-19 temporarily. Briefly, main reason for not stopping was that if the transplant will not proceed, the organ will be wasted. Focusing on SOT from living donors, 61% stated that activity should be restricted only to “urgent” cases. At the multivariate analysis, factors identified in favor of continuing transplant were Italy, ethicist, partially disagreeing on the equity question, a high number of COVID-19-related deaths on the day of the answer, a high IHDI country. Factors predicting to stop SOTs were Europe except-Italy, public university hospital, and strongly agreeing on the equity question.

Conclusions.

In conclusion, the majority of responders suggested that transplant activity should be continued through the implementation of isolation measures and the adoption of the COVID-19-free pathways. Differences between professional categories are less strong than supposed.
Automated contact tracing: a game of big numbers in the time of COVID-19
Authors: Kim Hyunju , Paul Ayan
Published: February 2021

One of the more widely advocated solutions for slowing down the spread of COVID-19 has been automated contact tracing. Since proximity data can be collected by personal mobile devices, the natural proposal has been to use this for automated contact tracing providing a major gain over a manual implementation. In this work, we study the characteristics of voluntary and automated contact tracing and its effectiveness for mapping the spread of a pandemic due to the spread of SARS-CoV-2. We highlight the infrastructure and social structures required for automated contact tracing to work. We display the vulnerabilities of the strategy to inadequate sampling of the population, which results in the inability to sufficiently determine significant contact with infected individuals. Of crucial importance will be the participation of a significant fraction of the population for which we derive a minimum threshold. We conclude that relying largely on automated contact tracing without population-wide participation to contain the spread of the SARS-CoV-2 pandemic can be counterproductive and allow the pandemic to spread unchecked. The simultaneous implementation of various mitigation methods along with automated contact tracing is necessary for reaching an optimal solution to contain the pandemic.
Proteolytic activity of the proteasome is required for female insect reproduction
Authors: Wang Wei , Yang Rui-Rui , Peng Lu-Yao , Zhang Lu , Yao Yue-Lin , Bao Yan-Yuan
Published: February 2021

Non-ATPase regulatory subunits (Rpns) are components of the 26S proteasome involved in polyubiquitinated substrate recognition and deubiquitination in eukaryotes. Here, we identified 15 homologues sequences of
Rpn
and associated genes by searching the genome and transcriptome databases of the brown planthopper,
Nilaparvata lugens
, a hemipteran rice pest. Temporospatial analysis showed that
NlRpn
genes were significantly highly expressed in eggs and ovaries but were less-highly expressed in males. RNA interference-mediated depletion of
NlRpn
genes decreased the proteolytic activity of proteasome and impeded the transcription of
lipase
and
vitellogenin
genes in the fat bodies and ovaries in adult females, and reduced the triglyceride content in the ovaries. Decrease of the proteolytic activity of the proteasome via knockdown of
NlRpn
s also inhibited the transcription of
halloween
genes, including
NlCYP307A2
,
NlCYP306A2
and
NlCYP314A1
, in the 20-hydroxyecdysone (20E) biosynthetic pathway in the ovaries, reduced 20E production in adult females, and impaired ovarian development and oocyte maturation, resulting in reduced fecundity. These novel findings indicate that the proteolytic activity of the proteasome is required for female reproductive processes in
N. lugens
, thus furthering our understanding of the reproductive and developmental strategies in insects.
The origin of animals: an ancestral reconstruction of the unicellular-to-multicellular transition
Authors: Ros-Rocher Núria , Pérez-Posada Alberto , Leger Michelle M. , Ruiz-Trillo Iñaki
Published: February 2021

How animals evolved from a single-celled ancestor, transitioning from a unicellular lifestyle to a coordinated multicellular entity, remains a fascinating question. Key events in this transition involved the emergence of processes related to cell adhesion, cell–cell communication and gene regulation. To understand how these capacities evolved, we need to reconstruct the features of both the last common multicellular ancestor of animals and the last unicellular ancestor of animals. In this review, we summarize recent advances in the characterization of these ancestors, inferred by comparative genomic analyses between the earliest branching animals and those radiating later, and between animals and their closest unicellular relatives. We also provide an updated hypothesis regarding the transition to animal multicellularity, which was likely gradual and involved the use of gene regulatory mechanisms in the emergence of early developmental and morphogenetic plans. Finally, we discuss some new avenues of research that will complement these studies in the coming years.
Synthesis and pharmacological characterization of glucopyranosyl-conjugated benzyl derivatives as novel selective cytotoxic agents against colon cancer
Authors: Fu Boqiao , Li Yingjie , Peng Shaoyong , Wang Xiaolin , Hu Jingying , Lv Long , Xia Caifen , Lu Dai , Qin Caiqin
Published: February 2021

Glucopyranosyl-conjugated benzyl derivatives containing a [1,2,3]-triazole linker were synthesized. Benzyl served as an important pharmacophore in anti-cancer compounds. Compound
8d
inhibited the proliferation of colorectal cancer cells with the potency comparable to 5-fluorouracil (5-FU) with improved selectivity towards cancer cells. The antiproliferative activity of
8d
is achieved through triggering apoptotic cell death.
Network geometry and market instability
Authors: Samal Areejit , Pharasi Hirdesh K. , Ramaia Sarath Jyotsna , Kannan Harish , Saucan Emil , Jost Jürgen , Chakraborti Anirban
Published: February 2021

The complexity of financial markets arise from the strategic interactions among agents trading stocks, which manifest in the form of vibrant correlation patterns among stock prices. Over the past few decades, complex financial markets have often been represented as networks whose interacting pairs of nodes are stocks, connected by edges that signify the correlation strengths. However, we often have interactions that occur in groups of three or more nodes, and these cannot be described simply by pairwise interactions but we also need to take the relations between these interactions into account. Only recently, researchers have started devoting attention to the higher-order architecture of complex financial systems, that can significantly enhance our ability to estimate systemic risk as well as measure the robustness of financial systems in terms of market efficiency. Geometry-inspired network measures, such as the Ollivier–Ricci curvature and Forman–Ricci curvature, can be used to capture the network fragility and continuously monitor financial dynamics. Here, we explore the utility of such discrete Ricci curvatures in characterizing the structure of financial systems, and further, evaluate them as generic indicators of the market instability. For this purpose, we examine the daily returns from a set of stocks comprising the USA S&P-500 and the Japanese Nikkei-225 over a 32-year period, and monitor the changes in the edge-centric network curvatures. We find that the different geometric measures capture well the system-level features of the market and hence we can distinguish between the normal or ‘business-as-usual’ periods and all the major market crashes. This can be very useful in strategic designing of financial systems and regulating the markets in order to tackle financial instabilities.
Unsteady Reynolds-averaged Navier–Stokes investigation of free surface wave impact on tidal turbine wake
Authors: Li Zhisong , Ghia Kirti , Li Ye , Fan Zhun , Shen Lian
Published: February 2021

Tidal current is a promising renewable energy source. Previous studies have investigated the influence of surface waves on tidal turbines in many aspects. However, the turbine wake development in a surface wave environment, which is crucial for power extraction in a turbine array, remains elusive. In this study, we focus on the wake evolution behind a single turbine and its interaction with surface waves. A numerical solver is developed to study the effects of surface waves on an industrial-size turbine. A case without surface wave and two cases with waves and different rotor depths are investigated. We obtain three-dimensional flow field descriptions near the free surface, around the rotor, and in the near- and far-wake. In a comparative analysis, the time-averaged and instantaneous flow fields are examined for various flow characteristics, including momentum restoration, power output, free surface elevation and vorticity dynamics. A model reduction technique is employed to identify the coherent flow structures and investigate the spatial and temporal characteristics of the wave–wake interactions. The results indicate the effect of surface waves in augmenting wake restoration and reveal the interactions between the surface waves and the wake structure, through a series of dynamic processes and the Kelvin–Helmholtz instability.
Exact closed-form and asymptotic expressions for the electrostatic force between two conducting spheres
Authors: Banerjee Shubho , Peters Thomas , Brown Nolan , Song Yi
Published: February 2021

We present exact closed-form expressions and complete asymptotic expansions for the electrostatic force between two charged conducting spheres of arbitrary sizes. Using asymptotic expansions of the force, we confirm that even like-charged spheres attract each other at sufficiently small separation unless their voltages/charges are the same as they would be at contact. We show that for sufficiently large size asymmetries, the repulsion between two spheres
increases
when they separate from contact if their voltages or their charges are held constant. Additionally, we show that in the constant voltage case, this like-voltage repulsion can be further increased and maximized through an optimal
lowering
of the voltage on the larger sphere at an optimal sphere separation.
Koala methylomes reveal divergent and conserved DNA methylation signatures of X chromosome regulation
Authors: Singh Devika , Sun Dan , King Andrew G. , Alquezar-Planas David E. , Johnson Rebecca N. , Alvarez-Ponce David , Yi Soojin V.
Published: February 2021

X chromosome inactivation (XCI) mediated by differential DNA methylation between sexes is an iconic example of epigenetic regulation. Although XCI is shared between eutherians and marsupials, the role of DNA methylation in marsupial XCI remains contested. Here, we examine genome-wide signatures of DNA methylation across fives tissues from a male and female koala (
Phascolarctos cinereus
), and present the first whole-genome, multi-tissue marsupial ‘methylome atlas’. Using these novel data, we elucidate divergent versus common features of representative marsupial and eutherian DNA methylation. First, tissue-specific differential DNA methylation in koalas primarily occurs in gene bodies. Second, females show significant global reduction (hypomethylation) of X chromosome DNA methylation compared to males. We show that this pattern is also observed in eutherians. Third, on average, promoter DNA methylation shows little difference between male and female koala X chromosomes, a pattern distinct from that of eutherians. Fourth, the sex-specific DNA methylation landscape upstream of
Rsx
, the primary
lnc
RNA associated with marsupial XCI, is consistent with the epigenetic regulation of female-specific (and presumably inactive X chromosome-specific) expression. Finally, we use the prominent female X chromosome hypomethylation and classify 98 previously unplaced scaffolds as X-linked, contributing an additional 14.6 Mb (21.5%) to genomic data annotated as the koala X chromosome. Our work demonstrates evolutionarily divergent pathways leading to functionally conserved patterns of XCI in two deep branches of mammals.
Functional genetic diversity in an exploited marine species and its relevance to fisheries management
Authors: Petrou Eleni L. , Fuentes-Pardo Angela P. , Rogers Luke A. , Orobko Melissa , Tarpey Carolyn , Jiménez-Hidalgo Isadora , Moss Madonna L. , Yang Dongya , Pitcher Tony J. , Sandell Todd , Lowry Dayv , Ruzzante Daniel E. , Hauser Lorenz
Published: February 2021

The timing of reproduction influences key evolutionary and ecological processes in wild populations. Variation in reproductive timing may be an especially important evolutionary driver in the marine environment, where the high mobility of many species and few physical barriers to migration provide limited opportunities for spatial divergence to arise. Using genomic data collected from spawning aggregations of Pacific herring (Clupea pallasii) across 1600 km of coastline, we show that reproductive timing drives population structure in these pelagic fish. Within a specific spawning season, we observed isolation by distance, indicating that gene flow is also geographically limited over our study area. These results emphasize the importance of considering both seasonal and spatial variation in spawning when delineating management units for herring. On several chromosomes, we detected linkage disequilibrium extending over multiple Mb, suggesting the presence of chromosomal rearrangements. Spawning phenology was highly correlated with polymorphisms in several genes, in particularSYNE2, which influences the development of retinal photoreceptors in vertebrates.SYNE2is probably within a chromosomal rearrangement in Pacific herring and is also associated with spawn timing in Atlantic herring (Clupea harengus). The observed genetic diversity probably underlies resource waves provided by spawning herring. Given the ecological, economic and cultural significance of herring, our results support that conserving intraspecific genetic diversity is important for maintaining current and future ecosystem processes.
Single-cell immune repertoire and transcriptome sequencing reveals that clonally expanded and transcriptionally distinct lymphocytes populate the aged central nervous system in mice
Authors: Yermanos Alexander , Neumeier Daniel , Sandu Ioana , Borsa Mariana , Waindok Ann Cathrin , Merkler Doron , Oxenius Annette , Reddy Sai T.
Published: February 2021

Neuroinflammation plays a crucial role during ageing and various neurological conditions, including Alzheimer's disease, multiple sclerosis and infection. Technical limitations, however, have prevented an integrative analysis of how lymphocyte immune receptor repertoires and their accompanying transcriptional states change with age in the central nervous system. Here, we leveraged single-cell sequencing to simultaneously profile B cell receptor and T cell receptor repertoires and accompanying gene expression profiles in young and old mouse brains. We observed the presence of clonally expanded B and T cells in the central nervous system of aged male mice. Furthermore, many of these B cells were of the IgM and IgD isotypes, and had low levels of somatic hypermutation. Integrating gene expression information additionally revealed distinct transcriptional profiles of these clonally expanded lymphocytes. Our findings implicate that clonally related T and B cells in the CNS of elderly mice may contribute to neuroinflammation accompanying homeostatic ageing.
Long-term change in the parasite burden of shore crabs (
Hemigrapsus oregonensis
and
Hemigrapsus nudus
) on the northwestern Pacific coast of North America
Authors: Quinn Jessica , Lee Sarah , Greeley Duncan , Gehman Alyssa , Kuris Armand M. , Wood Chelsea L.
Published: February 2021

The abundances of free-living species have changed dramatically in recent decades, but little is known about change in the abundance of parasitic species. We investigated whether populations of several parasites have shifted over time in two shore crab hosts,
Hemigrapsus oregonensis
and
Hemigrapsus nudus,
by comparing the prevalence and abundance of three parasite taxa in a historical dataset (1969–1970) to contemporary parasite abundance (2018–2020) for hosts collected from 11 intertidal sites located from Oregon, USA, to British Columbia, Canada. Our data suggest that the abundance of the parasitic isopod
Portunion conformis
has varied around a stable mean for the past 50 years. No change over time was observed for larval acanthocephalans. However, larval microphallid trematodes increased in prevalence over time among
H. oregonensis
hosts, from a mean of 8.4–61.8% between the historical and contemporary time points. The substantial increase in the prevalence of larval microphallid trematodes could be owing to increased abundances of their bird final hosts, increased production of parasite infective stages by snail intermediate hosts or both. Our study highlights the variability among parasite species in their temporal trajectories of change.