bluuebunny/crossref_metadata_2025 huggingface dataset:
Phylogeography of the stoneflyKamimuria tibialis: multiple glacial refugia and sympatric occurrence of different lineages in the southern islands of Japan
Authors: Otsuki Akiko , Yoshizawa Kazunori , Akimoto Shin-Ichi
Published: April 2021

To elucidate the effect of Pleistocene climatic fluctuations on the historical distribution and geographical genetic structure of temperate Japanese species, we performed phylogeographical and demographic analyses using mitochondrial gene sequences obtained from the stonefly species Kamimuria tibialis, sampled from four main islands of the Japanese Archipelago (i.e. Hokkaido, Honshu, Shikoku and Kyushu) and Tsushima Island. We detected three main clades with distinct geographical distributions, including the Tsushima, Kyushu and Hokkaido–Honshu–Shikoku phylogroups. These groups were estimated to have diverged from one another 0.54–2.02 Mya, suggesting they have undergone several glacial cycles in different refugia. Our results showed that during the glacial epochs and with a fall in sea-level, gene flow was limited among Tsushima and Kyushu, and among Hokkaido and Honshu, probably because the straits between these islands are deep. The population in Kyushu and Shikoku, the southernmost islands, exhibited high genetic diversity, with two distinct haplotype lineages occurring sympatrically. These results suggest that the population division into multiple refugia and the existence of stable southern refugia have contributed to the high genetic diversity of the species in this region.
Dynamic iridescent signals of male copperwing damselflies coupled with wing-clapping displays: the perspective of different receivers
Authors: Cezário Rodrigo Roucourt , Lopez Vinicius Marques , Gorb Stanislav , Guillermo-Ferreira Rhainer
Published: April 2021

Dynamic signals are a widespread phenomenon in several taxa, usually associated with intraspecific communication. In contrast, dynamic iridescent signals are detectable only at specific angles of illumination; hence, the animal can hide the signal to avoid detection when necessary. This structural coloration is mostly dependent on the illumination, the contrast against the background and the vision of the receiver. Complex behavioural displays can be coupled with structural coloration to create dynamic visual signals that enhance these functions. Here, we address whether iridescence of the males of a damselfly that inhabits dark rainforests, Chalcopteryx scintillans, can be considered a dynamic visual signal. We analyse whether coloration is perceived by conspecifics, while reducing detectability to eavesdroppers against three types of backgrounds. Our results suggest that the visual background affects the detectability of male hindwings by different receivers, mostly predators and prey. We discuss whether these results and the angle dependence of colour could indicate a mechanism to avoid unwanted intraspecific interactions or even to lure both predators and prey. We conclude that the main functions of the dynamic iridescent signal are to communicate with conspecifics while hindering the signal for prey, adding evidence of the multifunctionality of structural coloration coupled with behavioural displays in animals.
Maternal and genetic correlations between morphology and physical performance traits in a small captive primate,Microcebus murinus
Authors: Zablocki-Thomas Pauline , Lailvaux Simon , Aujard Fabienne , Pouydebat Emmanuelle , Herrel Anthony
Published: April 2021

Physical performance traits are key components of fitness and direct targets of selection. Although maternal effects have important influences on integrated phenotypes, their contributions to variation in performance and to phenotypic traits associated with performance remain poorly understood. We used an animal model to quantify the contribution of maternal effects to performance trait variation, in addition to the genetic and maternal correlations between performance and the relevant underlying morphology in Microcebus murinus. We showed that bite force is heritable (h2 ≈ 0.23) and that maternal effects are an important source of variation, resulting in a medium inclusive heritability (IH2 ≈ 0.47). Bite force and head depth showed a significant genetic correlation (0.70), and other genetic correlations were generally high (0.63 for bite force and head width; 0.41 for pull strength and radius length, albeit not significant), as were the maternal correlations for bite force and head dimensions (0.44, 0.73 and 0.29). Finally, we found differences in evolvability for pull strength and bite force that were also consistent with a higher potential for evolutionary change in pull force. This demonstrates clear effects of the maternal environment on performance expression and on the relationships between morphology and performance. This illustrates the importance of accounting for maternal identity when considering the heritabilities of functional traits.
Police Union Political Communications in Canada
Authors: Duncan Jamie , Walby Kevin
Published: April 2021

The political communications of police unions in the digital age deserve more attention from criminologists. This article examines the communications of two Canadian police associations in Toronto and Winnipeg. Using multimodal discourse analysis, we describe how police unions tactically engage with multiple forms of media to disseminate strategic narratives that reflect police identity and ideology. We conceptualize the mobilization of ‘thin blue line’ narratives and maintenance of a ‘blue wall of silence’ as forms of boundary work, which serve to favourably delineate the role of police in their communities while sidestepping critical views. The proliferation of digital media amplifies the unions’ capacities to influence local politics by undermining elected authorities and community activists while advancing a police-centric view of society.
Gynostemium structure and development in subtribe Spiranthinae (Cranichideae, Orchidaceae)
Authors: Figueroa Coyolxauhqui , Terrazas Teresa , Dávila Patricia , Salazar Gerardo A
Published: April 2021

We analysed gynostemium development and morphology of 13 species of Spiranthinae to understand the structure and homology of this organ. Flowers and flower buds in different developmental stages were examined with scanning electron and light microscopy. Gynostemium ontogeny is similar in the early stages among the analysed species, and most of the differences arose at later developmental stages. Gynostemium development starts with the appearance of the anther primordium, followed by the median carpel and finally by the lateral carpel apices. The last emerges as two congenitally united, crescent-shaped prominences located between the median carpel apex and the labellum, eventually forming a rim of tissue on the proximal margin of the stigma. The rim can be receptive or not. The base of the median carpel apex contributes mostly to the receptive stigmatic zone and its apical region develops into the viscidium. The entrance of the stylar canal is located between the two partially non-receptive lateral carpel apices and the receptive base of the median carpel apex, refuting the idea that in Sarcoglottis it is located above the stigmatic area. There are no staminodal primordia, and the membranaceous appendages at each side of the column apex represent extensions of the clinandrium margins.
Human Immunodeficiency Virus Infection in Adolescents and Mode of Transmission in Southern Africa: A Multinational Analysis of Population-Based Survey Data
Authors: Low Andrea , Teasdale Chloe , Brown Kristin , Barradas Danielle T , Mugurungi Owen , Sachathep Karam , Nuwagaba-Biribonwoha Harriet , Birhanu Sehin , Banda Andrew , Frederix Koen , Payne Danielle , Radin Elizabeth , Wiesner Lubbe , Ginindza Choice , Philip Neena , Musuka Godfrey , Sithole Sakhile , Patel Hetal , Maile Limpho , Abrams Elaine J , Arpadi Stephen
Published: April 2021

Background

Adolescents aged 10–19 years living with human immunodeficiency virus (HIV) (ALHIV), both perinatally infected adolescents (APHIV) and behaviorally infected adolescents (ABHIV), are a growing population with distinct care needs. We characterized the epidemiology of HIV in adolescents included in Population-based HIV Impact Assessments (2015–2017) in Zimbabwe, Malawi, Zambia, Eswatini, and Lesotho.

Methods

Adolescents were tested for HIV using national rapid testing algorithms. Viral load (VL) suppression (VLS) was defined as VL <1000 copies/mL, and undetectable VL (UVL) as VL <50 copies/mL. Recent infection (within 6 months) was measured using a limiting antigen avidity assay, excluding adolescents with VLS or with detectable antiretrovirals (ARVs) in blood. To determine the most likely mode of infection, we used a risk algorithm incorporating recency, maternal HIV and vital status, history of sexual activity, and age at diagnosis.

Results

HIV prevalence ranged from 1.6% in Zambia to 4.8% in Eswatini. Of 707 ALHIV, 60.9% (95% confidence interval, 55.3%–66.6%) had HIV previously diagnosed, and 47.1% (41.9%–52.3%) had VLS. Our algorithm estimated that 72.6% of ALHIV (485 of 707) were APHIV, with HIV diagnosed previously in 69.5% of APHIV and 39.4% of ABHIV, and with 65.3% of APHIV and 33.5% of ABHIV receiving ARV treatment. Only 67.2% of APHIV and 60.5% of ABHIV receiving ARVs had UVL.

Conclusions

These findings suggest that two-thirds of ALHIV were perinatally infected, with many unaware of their status. The low prevalence of VLS and UVL in those receiving treatment raises concerns around treatment effectiveness. Expansion of opportunities for HIV diagnoses and the optimization of treatment are imperative.
Effectiveness of Messenger RNA Coronavirus Disease 2019 (COVID-19) Vaccines Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in a Cohort of Healthcare Personnel
Authors: Swift Melanie D , Breeher Laura E , Tande Aaron J , Tommaso Christopher P , Hainy Caitlin M , Chu Haitao , Murad M Hassan , Berbari Elie F , Virk Abinash
Published: April 2021

In a large cohort of United States healthcare personnel without prior coronavirus disease 2019 (COVID-19) infection, 94 382 doses of messenger RNA (mRNA) COVID-19 vaccine were administered to 49 220 individuals. The adjusted vaccine effectiveness following 2 doses of each of the 2 available brands of mRNA vaccine exceeded 96%.
Moving on From HAND: Why We Need New Criteria for Cognitive Impairment in Persons Living With Human Immunodeficiency Virus and a Proposed Way Forward
Authors: Nightingale Sam , Dreyer Anna J , Saylor Deanna , Gisslén Magnus , Winston Alan , Joska John A
Published: April 2021

Human immunodeficiency virus (HIV)–associated neurocognitive disorders (HAND) criteria are frequently used to describe cognitive impairment in persons living with HIV (PLWH) across diverse populations globally. These criteria typically find 20–60% of PLWH meet criteria for HAND, which does not tally with clinical observations in the modern era that cognitive disorders present relatively infrequently. Most with HAND have asymptomatic neurocognitive impairment; however, the significance of low cognitive test performance without symptoms is uncertain. Methods underlying HAND criteria carry a false-positive rate that can exceed 20%. Comorbidities, education, and complex socioeconomic factors can influence cognitive test performance, further increasing the potential for misclassification. We propose a new framework to characterize cognitive impairment in PLWH that requires a clinical history and acknowledges the multifactorial nature of low cognitive test performance. This framework is intended to be applicable across diverse populations globally, be more aligned with clinical observations, and more closely represent HIV brain pathology.
Menstrual Toxic Shock Syndrome: A French Nationwide Multicenter Retrospective Study
Authors: Contou Damien , Colin Gwenhaël , Travert Brendan , Jochmans Sébastien , Conrad Marie , Lascarrou Jean-Baptiste , Painvin Benoit , Ferré Alexis , Schnell David , La Combe Beatrice , Coudroy Rémi , Ehrmann Stephan , Rambaud Jérôme , Wiedemann Arnaud , Asfar Pierre , Kalfon Pierre , Guérot Emmanuel , Préau Sébastien , Argaud Laurent , Daviet Florence , Dellamonica Jean , Dupont Audrey , Fartoukh Muriel , Kamel Toufik , Béduneau Gaëtan , Canouï-Poitrine Florence , Boutin Emmanuelle , Lina Gérard , Mekontso Dessap Armand , Tristan Anne , de Prost Nicolas ,   French m-TSS Study Group, Colin G , Travert B , Jochmans S , Conrad M , Lascarrou J B , de Prost N , Painvin B , Ferré A , Schnell D , La Combe B , Coudroy R , Ehrmann S , Rambaud J , Wiedemann A , Asfar P , Contou D , Kalfon P , Daviet F , Préau S , Argaud L , Dellamonica J , Kamel T , Béduneau G , Fartoukh M , Dupont A , Sinnah F , Hamou Z Ait , Quenot J P , Moine P , Bourenne J , Guérot E , Mégarbane B , Reuter D , Galbois A , Beuret P , Bruel C , Isnard M , Delbove A , Sztrymf B , Thyrault M , Recher M , Mortamet G
Published: April 2021

Background

Studies describing the clinical features and short-term prognosis of patients admitted to the intensive care unit (ICU) for menstrual toxic shock syndrome (m-TSS) are lacking.

Methods

This was a multicenter retrospective cohort study of patients with a clinical diagnosis of m-TSS admitted between 1 January 2005 and 31 December 2020 in 43 French pediatric (n = 7) or adult (n = 36) ICUs. The aim of the study was to describe the clinical features and short-term prognosis, as well as to assess the 2011 Centers for Disease and Control (CDC) diagnostic criteria, in critically ill patients with m-TSS.

Results

In total, 102 patients with m-TSS (median age, 18 years; interquartile range, 16–24 years) were admitted to 1 of the participating ICUs. All blood cultures (n = 102) were sterile. Methicillin-sensitive Staphylococcus aureus grew from 92 of 96 vaginal samples. Screening for superantigenic toxin gene sequences was performed for 76 of the 92 vaginal samples positive for S. aureus (83%), and toxic shock syndrome toxin 1 was isolated from 66 strains (87%). At ICU admission, no patient met the 2011 CDC criteria for confirmed m-TSS, and only 53 (52%) fulfilled the criteria for probable m-TSS. Eighty-one patients (79%) were treated with antitoxin antibiotic therapy, and 8 (8%) received intravenous immunoglobulins. Eighty-six (84%) patients required vasopressors, and 21 (21%) tracheal intubation. No patient required limb amputation or died in the ICU.

Conclusions

In this large multicenter series of patients included in ICUs for m-TSS, none died or required limb amputation. The CDC criteria should not be used for the clinical diagnosis of m-TSS at ICU admission.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Sequence Characteristics of Coronavirus Disease 2019 (COVID-19) Persistence and Reinfection
Authors: Choudhary Manish C , Crain Charles R , Qiu Xueting , Hanage William , Li Jonathan Z
Published: April 2021

Background

Both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection and persistent infection have been reported, but sequence characteristics in these scenarios have not been described. We assessed published cases of SARS-CoV-2 reinfection and persistence, characterizing the hallmarks of reinfecting sequences and the rate of viral evolution in persistent infection.

Methods

A systematic review of PubMed was conducted to identify cases of SARS-CoV-2 reinfection and persistence with available sequences. Nucleotide and amino acid changes in the reinfecting sequence were compared with both the initial and contemporaneous community variants. Time-measured phylogenetic reconstruction was performed to compare intrahost viral evolution in persistent SARS-CoV-2 to community-driven evolution.

Results

Twenty reinfection and 9 persistent infection cases were identified. Reports of reinfection cases spanned a broad distribution of ages, baseline health status, reinfection severity, and occurred as early as 1.5 months or >8 months after the initial infection. The reinfecting viral sequences had a median of 17.5 nucleotide changes with enrichment in the ORF8 and N genes. The number of changes did not differ by the severity of reinfection and reinfecting variants were similar to the contemporaneous sequences circulating in the community. Patients with persistent coronavirus disease 2019 (COVID-19) demonstrated more rapid accumulation of sequence changes than seen with community-driven evolution with continued evolution during convalescent plasma or monoclonal antibody treatment.

Conclusions

Reinfecting SARS-CoV-2 viral genomes largely mirror contemporaneous circulating sequences in that geographic region, while persistent COVID-19 has been largely described in immunosuppressed individuals and is associated with accelerated viral evolution.
Substantial Decline in Invasive Pneumococcal Disease During Coronavirus Disease 2019 Pandemic in Hong Kong
Authors: Teng Jade L L , Fok Kenny M N , Lin Ken P K , Chan Elaine , Ma Yuanchao , Lau Susanna K P , Woo Patrick C Y
Published: April 2021

Compared with other countries, a more substantial decrease in the incidence of invasive pneumococcal disease was observed in Hong Kong, which is most likely attributable to the proactive mass adoption of face masks by the public. Human behavioral changes, particularly mask wearing, should be considered as an additional preventive strategy against invasive pneumococcal disease.
Severity Level Classification of Brain Tumor based on MRI Images using Fractional-Chicken Swarm Optimization Algorithm
Authors: Cristin Dr R , Kumar Dr K Suresh , Anbhazhagan Dr P
Published: April 2021

Brain tumor classification is highly effective in identifying and diagnosing the exact location of the tumor in the brain. The medical imaging system reported that early diagnosis and classification of the tumor increases the life of the human. Among various imaging modalities, magnetic resonance imaging (MRI) is highly used by clinical experts, as it offers contrast information of brain tumors. An effective classification method named fractional-chicken swarm optimization (fractional-CSO) is introduced to perform the severity-level tumor classification. Here, the chicken swarm behavior is merged with the derivative factor to enhance the accuracy of severity level classification. The optimal solution is obtained by updating the position of the rooster, which updates their location based on better fitness value. The brain images are pre-processed and the features are effectively extracted, and the cancer classification is carried out. Moreover, the severity level of tumor classification is performed using the deep recurrent neural network, which is trained by the proposed fractional-CSO algorithm. Moreover, the performance of the proposed fractional-CSO attained better performance in terms of the evaluation metrics, such as accuracy, specificity and sensitivity with the values of 93.35, 96 and 95% using simulated BRATS dataset, respectively.
Guess-and-Determine Attacks on AEGIS
Authors: Jiao Lin , Li Yongqiang , Du Shaoyu
Published: April 2021

AEGIS is one of the authenticated encryption with associated data designs selected for the final portfolio of the CAESAR competition. It combines the AES round function and simple Boolean operations to update its large state and extract a keystream to achieve an excellent software performance. The AEGIS family consists of AEGIS-128, AEGIS-256 and AEGIS-128L, which use 5, 6 and 8 parallel AES round functions to process 128, 128 and 256 bits message block per step with slightly different output functions separately. Surprisingly, very few cryptanalytic results on AEGIS have been published so far. This paper presents the first guess-and-determine attacks on AEGIS family. Firstly, we propose a new observation on the structure of AEGIS that the relations of fixed variables remain in the outputs at consecutive steps under some conditions on the AND operations, and the vectorial bitwise AND operation is biased, which is able to derive the additional variables added directly. Secondly, we add several techniques, such as divide and conquer on byte-based columns, reduction by meet in the middle and simplification through constraints on variables, for each AEGIS member. Finally, we conduct guess-and-determine attacks on AEGIS-128, AEGIS-256 and AEGIS-128L and result in a complexity of $2^{309}$, $2^{437}$ and $2^{384}$ to $2^{416}$, respectively. Although neither attack threatens the practical security of AEGIS, it has great significance to evaluate the resistance of such structure compared with their large internal state exploited of 640, 768 and 1024 bits. It is also the first internal state recovery attack on AEGIS without nonce reusing, while only distinguishing attacks on AEGIS exist up to now.
Performance Evaluation of Learning Models for Identification of Suicidal Thoughts
Authors: Chadha Akshma , Kaushik Baijnath
Published: April 2021

The suicidal death rate is growing rapidly. Depression and stress levels among the people have increased significantly, which is considered to be a risk factor for suicidal thoughts. Social media is gradually more popular and people use them for sharing their sentiments and harmful emotions related to suicidal thoughts. An effective approach is required to investigate for identifying risk factors associated with suicide on social media. The objective is to propose some learning models to evaluate social media data to identify persons having suicidal tendencies. A large data consisting of 8452 tweets are collected from Twitter, pre-processed and bags of words were applied. Different machine learning and deep learning algorithms such as Random Forest, Decision Tree, Bernoulli Naïve Bayes, Multinomial Naïve Bayes, Recurrent Neural Network, Artificial Neural Network and Long Short Term Memory were applied for classifying the tweets in two sets: suicidal and non-suicidal. The performance of these learning models is further evaluated on three parameters: accuracy, precision and recall. These models have shown significant results on the parameters.
Observations on the Security of COMET
Authors: Xu Zheng , Li Yongqiang , Wang Mingsheng
Published: April 2021

This paper investigates the security of counter mode encryption with authentication tag (COMET), one of the 32 second-round candidates in National Institute of Standards and Technology’s lightweight cryptography standardization process, against differential cryptanalysis. CHAM-64/128 is a block cipher chosen as one of the underlying block ciphers in COMET for hardware-oriented applications, and a differential characteristic with a high probability for CHAM-64/128 is useful for forgery attacks on COMET. However, we find that the optimal $\mathbf{39}$-round differential characteristic for CHAM-64/128 proposed by Roh et al., which is the longest differential characteristic of CHAM-64/128, is invalid. Then, we propose a new method of distinguishing an $\mathbf{m}$-bit block cipher from an $\mathbf{m}$-bit random permutation using a differential characteristic with a probability not higher than $\mathbf{2^{-m}}$. Using our method, we use two $\mathbf{39}$-round differential characteristics with a probability of $\mathbf{2^{-64}}$ for CHAM-64/128 to distinguish $\mathbf{39}$-round-reduced CHAM-64/128 from a $\mathbf{64}$-bit random permutation, respectively. Furthermore, we refine the probabilities of two differentials with the same input and output differential masks as the two $\mathbf{39}$-round differential characteristics, respectively. Finally, we present the first forgery attacks on COMET with the two differentials without using weak keys. Our forgery attacks follow the nonce-misuse scenario. It should be noticed that this attack does not invalidate the security claims of the designers.
Deficiency of myeloid PHD proteins aggravates atherogenesis via macrophage apoptosis and paracrine fibrotic signalling
Authors: van Kuijk Kim , Demandt Jasper A F , Perales-Patón Javier , Theelen Thomas L , Kuppe Christoph , Marsch Elke , de Bruijn Jenny , Jin Han , Gijbels Marion J , Matic Ljubica , Mees Barend M E , Reutelingsperger Chris P M , Hedin Ulf , Biessen Erik A L , Carmeliet Peter , Baker Andrew H , Kramann Rafael K , Schurgers Leon J , Saez-Rodriguez Julio , Sluimer Judith C
Published: April 2021

Aims

Atherosclerotic plaque hypoxia is detrimental for macrophage function. Prolyl hydroxylases (PHDs) initiate cellular hypoxic responses, possibly influencing macrophage function in plaque hypoxia. Thus, we aimed to elucidate the role of myeloid PHDs in atherosclerosis.

Methods and results

Myeloid-specific PHD knockout (PHDko) mice were obtained via bone marrow transplantation (PHD1ko, PHD3ko) or conditional knockdown through lysozyme M-driven Cre recombinase (PHD2cko). Mice were fed high cholesterol diet for 6–12 weeks to induce atherosclerosis. Aortic root plaque size was significantly augmented 2.6-fold in PHD2cko, and 1.4-fold in PHD3ko compared to controls but was unchanged in PHD1ko mice. Macrophage apoptosis was promoted in PHD2cko and PHD3ko mice in vitro and in vivo, via the hypoxia-inducible factor (HIF) 1α/BNIP3 axis. Bulk and single-cell RNA data of PHD2cko bone marrow-derived macrophages (BMDMs) and plaque macrophages, respectively, showed enhanced HIF1α/BNIP3 signalling, which was validated in vitro by siRNA silencing. Human plaque BNIP3 mRNA was positively associated with plaque necrotic core size, suggesting similar pro-apoptotic effects in human. Furthermore, PHD2cko plaques displayed enhanced fibrosis, while macrophage collagen breakdown by matrix metalloproteinases, collagen production, and proliferation were unaltered. Instead, PHD2cko BMDMs enhanced fibroblast collagen secretion in a paracrine manner. In silico analysis of macrophage-fibroblast communication predicted SPP1 (osteopontin) signalling as regulator, which was corroborated by enhanced plaque SPP1 protein in vivo. Increased SPP1 mRNA expression upon PHD2cko was preferentially observed in foamy plaque macrophages expressing ‘triggering receptor expressed on myeloid cells-2’ (TREM2hi) evidenced by single-cell RNA, but not in neutrophils. This confirmed enhanced fibrotic signalling by PHD2cko macrophages to fibroblasts, in vitro as well as in vivo.

Conclusion

Myeloid PHD2cko and PHD3ko enhanced atherosclerotic plaque growth and macrophage apoptosis, while PHD2cko macrophages further activated collagen secretion by fibroblasts in vitro, likely via paracrine SPP1 signalling through TREM2hi macrophages.
Ustekinuma b for Crohn’s Disease: Two-Year Results of the Initiative on Crohn and Colitis (ICC) Registry, a Nationwide Prospective Observational Cohort Study
Authors: Straatmijer Tessa , Biemans Vince B C , Hoentjen Frank , de Boer Nanne K H , Bodelier Alexander G L , Dijkstra Gerard , van Dop Willemijn A , Haans Jeoffrey J L , Jansen Jeroen M , Maljaars P W Jeroen , van der Marel Sander , Oldenburg Bas , Ponsioen Cyriel Y , Visschedijk Marijn C , de Vries Annemarie C , West Rachel L , van der Woude C Janneke , Pierik Marieke , Duijvestein Marjolijn , van der Meulen-de Jong Andrea E
Published: April 2021

Aims

Ustekinumab is a monoclonal antibody that selectively targets p40, a shared subunit of the cytokines interleukin [IL]-12 and IL-23. It is registered for the treatment of inflammatory bowel diseases. We assessed the 2-year effectiveness and safety of ustekinumab in a real world, prospective cohort of patients with Crohn’s disease [CD].

Methods

Patients who started ustekinumab were prospectively enrolled in the nationwide Initiative on Crohn and Colitis [ICC] Registry. At weeks 0, 12, 24, 52 and 104, clinical remission Harvey Bradshaw Index≤ 4 points], biochemical remission (faecal calprotectin ≤ 200 μg/g and/or C-reactive protein ≤5 mg/L], perianal fistula remission, extra-intestinal manifestations, ustekinumab dosage and safety outcomes were determined. The primary outcome was corticosteroid-free clinical remission at week 104.

Results

In total, 252 CD patients with at least 2 years of follow-up were included. Of all included patients, the proportion of patients in corticosteroid-free clinical remission was 32.3% [81/251], 41.4% [104/251], 39% [97/249] and 34.0% [84/247] at weeks 12, 24, 52 and 104, respectively. In patients with combined clinical and biochemical disease activity at baseline [n = 122], the corticosteroid-free clinical remission rates were 23.8% [29/122], 35.2% [43/122], 40.0% [48/120] and 32.8% [39/119] at weeks 12, 24, 52 and 104, respectively. The probability of remaining on ustekinumab treatment after 52 and 104 weeks in all patients was 64.3% and 54.8%, respectively. The main reason for discontinuing treatment after 52 weeks was loss of response [66.7%]. No new safety issues were observed.

Conclusion

After 104 weeks of ustekinumab treatment, one-third of CD patients were in corticosteroid-free clinical remission.
Implications of abnormal ascending aorta geometry for risk prediction of acute type A aortic dissection
Authors: Della Corte Alessandro , Rubino Antonino Salvatore , Montella Antonio Pio , Bancone Ciro , Lo Presti Federica , Galbiati Denise , Dialetto Giovanni , De Feo Marisa
Published: April 2021

OBJECTIVES

Recently, increased length of the ascending aorta has been suggested as a possible risk factor for acute type A aortic dissection (ATAAD). Our goal was to identify measurable aortic geometrical characteristics associated with elongation that could differentiate ATAAD from uncomplicated aortic dilation (>45 mm).

METHODS

In angiographic computed tomography scans performed in 180 patients having cardiac surgery, aortic diameters, root length, length of the ascending aorta at both the centreline and the greater curvature (convexity) and the root-ascending (root-asc) angle (that between the root axis and the axis of the ascending tract) and the ascending-arch (asc-arch) angle (that between the axis of the ascending aorta and the arch axis) were measured and compared among 3 patient groups: normal aorta (diameter < 45 mm), dilation/aneurysm (>45 mm) and ATAAD. Correlations between diameters and angles, diameters and lengths and lengths and angles were analysed; multivariable analysis including geometrical factors was performed to identify independent predictors of ATAAD.

RESULTS

Both patients with aneurysms and patients with ATAAD showed significantly elongated ascending aortas (P < 0.001 vs normal). However, in the aneurysms, the root-asc angle (136° ± 20° vs 147° ± 17°; P < 0.001) and in ATAAD the asc-arch angle were uniquely narrower than that in the normal aorta (116° ± 11° vs 132° ± 19°; P < 0.001). All patients with an ATAAD had an asc-arch angle ≤130°. Both in patients with ATAAD and in those without ATAAD, narrowing of the asc-arch angle was associated with elongation of the root segment (P < 0.001). In multivariable analysis, the asc-arch angle and the total length of the ascending aorta (root + tubular) were significant predictors of ATAAD.

CONCLUSIONS

The asc-arch angle is a promising measurement that could help predict aortic dissection along with aortic diameter and length: further verification is warranted.
Can prosthesis type influence the recurrence of infective endocarditis after surgery for native valve endocarditis? A propensity weighted comparison
Authors: Rubino Antonino S , Della Ratta Ester E , Galbiati Denise , Ashurov Rasul , Galgano Viviana L , Montella Antonio P , De Feo Marisa , Della Corte Alessandro
Published: April 2021

OBJECTIVES

Our goal was to investigate whether the incidence of valve-related adverse events might be different depending on the valve substitute after valve replacement for left-sided native valve endocarditis.

METHODS

We assessed the long-term freedom from recurrence, reoperation and survival of 395 patients who had valve replacements for native valve endocarditis (314 mechanical vs 81 biological). Age <18 years, reoperation, prosthetic endocarditis, right valve involvement, valve repair and homograft implants were the main exclusion criteria. The balance between the 2 groups was addressed by weighting the results on the inverse of the propensity score.

RESULTS

After inverse probability of treatment weighting (IPTW), freedom from recurrence of infective endocarditis was not significantly different (mechanical 84.1 ± 3.2% vs 50.6 ± 21.7%; P = 0.29) nor was freedom from reoperation different (mechanical 85.7 ± 3.1% vs biological 50.9 ± 21.9%; P = 0.29). Excluding competing deaths, patients receiving a bioprosthesis had a similar subdistribution hazard of the above end points compared to recipients of a mechanical valve [recurrence IPTW: hazard ratio (HR) 1.631, 95% confidence interval (CI) 0.756–3.516; P = 0.21; reoperation IPTW-HR 1.737, 95% CI 0.780–3.870; P = 0.18]. Mechanical valves were associated with improved long-term survival (34.9 ± 5.8% vs 10.5 ± 7.4% at 30 years; P = 0.0009; in particular: aortic valve subgroup 41.6 ± 9.3% vs 10.1 ± 8.2%; P < 0.0001), although the hazard of cardiovascular mortality did not favour either valve type (IPTW: HR 1.361, 95% CI 0.771–2.404; P = 0.29).

CONCLUSIONS

Our analysis showed a clinical trend in favour of mechanical valves as valve substitutes for native valve endocarditis, especially in the aortic position. In view of long-term freedom from adverse events, the choice of the valve type should be tailored according to patient characteristics and specific clinical conditions.
Last-minute cancellation of adult patients scheduled for cardiothoracic surgery in a large Dutch tertiary care centre
Authors: Scheenstra Bart , Princée Anouk M A , Imkamp Maike S V , Kietselaer Bas , Ganushchak Yuri M , van’t Hof Arnoud W J , Maessen Jos G
Published: April 2021

OBJECTIVES

Unanticipated cancellation of a surgical procedure is a common problem, causing distress to the patient and increases in healthcare costs. However, limited evidence exists on the effects of last-minute cancellations of cardiothoracic surgical procedures in particular. The goal of this study was to gain insight into the prevalence of and the reasons for last-minute cancellations and to examine whether cancellation is associated with adverse medical outcomes.

METHODS

Patients who were scheduled for elective cardiothoracic surgical procedures between January 2017 and June 2019 were evaluated. The reasons for the cancellations were assigned to the categories medically related or process related. We examined the differences in patient characteristics between those designated as no cancellation, medically related cancellations and process-related cancellations. Lastly, we examined the outcomes of patients who experienced a last-minute cancellation of a scheduled operation.

RESULTS

A total of 2111 patients were included; of these, 301 (14.3%) had last-minute cancellations. In 78 (26%) cases, the cancellations were attributable to medical reasons (e.g. infection, comorbidities); 215 (71%) of the cancellations were process related (e.g. another patient in more urgent need of surgery, lack of staff). Almost 99% of the operations with a process-related cancellation were rescheduled compared to only 71.8% of the medically related cancelled operations (P < 0.001). Patients with a medically related cancellation had significantly higher 1-year mortality than patients who had no cancellation (unadjusted hazard ratio 2.50; 95% confidence interval, 1.30–4.78; P = 0.006); after adjustment for the EuroSCORE II, this effect remained significant.

CONCLUSIONS

Last-minute cancellations were commonly seen in our cohort, and the reasons for cancellation were significantly related to adverse medical outcomes.
Soil microbial interconnections along ecological restoration gradients of lowland forests after slash-and-burn agriculture
Authors: Lin Qiang , Dini-Andreote Francisco , Li Lingjuan , Umari Ruma , Novotny Vojtech , Kukla Jaroslav , Heděnec Petr , Frouz Jan
Published: April 2021

Microbial interconnections in soil are pivotal to ecosystem services and restoration. However, little is known about how soil microbial interconnections respond to slash-and-burn agriculture and to the subsequent ecosystem restoration after the practice. Here, we used amplicon sequencing and co-occurrence network analyses to explore the interconnections within soil bacterial and fungal communities in response to slash-and-burn practice and a spontaneous restoration (spanning ca. 60 years) of tropical forests after the practice, in Papua New Guinea. We found significantly higher complexity and greater variations in fungal networks than in those of bacteria, despite no significant changes observed in bacterial or fungal networks across successional stages. Within most successional stages, bacterial core co-occurrences (co-occurrences consistently present across all sub-networks in a stage) were more frequent than those of fungi, indicating higher stability of interconnections between bacteria along succession. The stable interconnections occurred frequently between bacterial taxa (i.e. Sporosarcina, Acidimicrobiale and Bacillaceae) and between ectomycorrhizal fungi (Boletaceae and Russula ochroleuca), implying important ecological roles of these taxa in the ecosystem restoration. Collectively, our results provide new insight into microbial interconnections in response to slash-and-burn agriculture and the subsequent ecosystem restoration, thus promoting a better understanding of microbial roles in ecosystem services and restoration.
Correlations between maximum reductive dechlorination rates and specific biomass parameters in Dehalococcoides mccartyi consortia enriched on chloroethenes PCE, TCE and cis-1,2-DCE
Authors: Matturro B , Majone M , Aulenta F , Rossetti S
Published: April 2021

One of the challenges to implementing the modeling of the biological reductive dechlorination (RD) process is the evaluation of biological parameters that represent the abundance/activity levels of the microorganisms involved in the biodegradation of chloroethenes. Here we report a combined analysis of kinetic and specific biomass parameters conducted on three dechlorinating consortia enriched on PCE, TCE and cis-1,2-DCE. In these consortia, Dehalococcoides mccartyi (Dhc) represented ≥70% of the bacterial population identified via 16S rRNA gene amplicon sequencing. Quantitative biomolecular methods were used to generate specific biomass parameters targeting either the Dhc population (16S rRNA genes or cells) or specific genes encoding RD process-involved reductive dehalogenases. The correlation factor between the abundance of active Dhc cells or tceA gene copies and maximum RD rates allowed to predict an increment of 7E+09 of active Dhc cells or 5E+09 tceA gene copies/L under controlled conditions. Diversely, the utilization of gene transcripts as biomass parameters for RD modeling did not provide reliable correlations with kinetic performances. This study provides valuable insights for further modeling of the RD process through the utilization of specific biomass parameters.
Expansion of EasyClone-MarkerFree toolkit for Saccharomyces cerevisiae genome with new integration sites
Authors: Babaei Mahsa , Sartori Luisa , Karpukhin Alexey , Abashkin Dmitrii , Matrosova Elena , Borodina Irina
Published: April 2021

Biotechnological production requires genetically stable recombinant strains. To ensure genomic stability, recombinant DNA is commonly integrated into the genome of the host strain. Multiple genetic tools have been developed for genomic integration into baker's yeast Saccharomyces cerevisiae. Previously, we had developed a vector toolkit EasyClone-MarkerFree for stable integration into eleven sites on chromosomes X, XI, and XII of S. cerevisiae. The markerless integration was enabled by CRISPR-Cas9 system. In this study, we have expanded the kit with eight additional intergenic integration sites located on different chromosomes. The integration efficiency into the new sites was above 80%. The expression level of green fluorescence protein (gfp) for all eight sites was similar or above XI-2 site from the original EasyClone-MarkerFree toolkit. The cellular growth was not affected by the integration into any of the new eight locations. The eight-vector expansion kit is available from AddGene.
Effects of kinship correction on inflation of genetic interaction statistics in commonly used mouse populations
Authors: Tyler Anna L , El Kassaby Baha , Kolishovski Georgi , Emerson Jake , Wells Ann E , Mahoney J Matthew , Carter Gregory W
Published: April 2021

It is well understood that variation in relatedness among individuals, or kinship, can lead to false genetic associations. Multiple methods have been developed to adjust for kinship while maintaining power to detect true associations. However, relatively unstudied are the effects of kinship on genetic interaction test statistics. Here, we performed a survey of kinship effects on studies of six commonly used mouse populations. We measured inflation of main effect test statistics, genetic interaction test statistics, and interaction test statistics reparametrized by the Combined Analysis of Pleiotropy and Epistasis (CAPE). We also performed linear mixed model (LMM) kinship corrections using two types of kinship matrix: an overall kinship matrix calculated from the full set of genotyped markers, and a reduced kinship matrix, which left out markers on the chromosome(s) being tested. We found that test statistic inflation varied across populations and was driven largely by linkage disequilibrium. In contrast, there was no observable inflation in the genetic interaction test statistics. CAPE statistics were inflated at a level in between that of the main effects and the interaction effects. The overall kinship matrix overcorrected the inflation of main effect statistics relative to the reduced kinship matrix. The two types of kinship matrices had similar effects on the interaction statistics and CAPE statistics, although the overall kinship matrix trended toward a more severe correction. In conclusion, we recommend using an LMM kinship correction for both main effects and genetic interactions and further recommend that the kinship matrix be calculated from a reduced set of markers in which the chromosomes being tested are omitted from the calculation. This is particularly important in populations with substantial population structure, such as recombinant inbred lines in which genomic replicates are used.
Spermiogenesis Initiation in Caenorhabditis elegans Involves a Casein Kinase 1 Encoded by the spe-6 Gene
Authors: Muhlrad Paul J , Ward Samuel
Published: April 2021

Immature spermatids from Caenorhabditis elegans are stimulated by an external activation signal to reorganize their membranes and cytoskeleton to form crawling spermatozoa. This rapid maturation, termed spermiogenesis, occurs without any new gene expression. To better understand this signal transduction pathway, we isolated suppressors of a mutation in the spe-27 gene, which is part of the pathway. The suppressors bypass the requirement for spe-27, as well as three other genes that act in this pathway, spe-8, spe-12, and spe-29. Eighteen of the suppressor mutations are new alleles of spe-6, a previously identified gene required for an early stage of spermatogenesis. The original spe-6 mutations are loss-of-function alleles that prevent major sperm protein (MSP) assembly in the fibrous bodies of spermatocytes and arrest development in meiosis. We have isolated the spe-6 gene and find that it encodes a predicted protein-serine/threonine kinase in the casein kinase 1 family. The suppressor mutations appear to be reduction-of-function alleles. We propose a model whereby SPE-6, in addition to its early role in spermatocyte development, inhibits spermiogenesis until the activation signal is received. The activation signal is transduced through SPE-8, SPE-12, SPE-27, and SPE-29 to relieve SPE-6 repression, thus triggering the formation of crawling spermatozoa.
Drosophila melanogaster Importin α1 and α3 Can Replace Importin α2 During Spermatogenesis but Not Oogenesis
Authors: Mason D Adam , Fleming Robert J , Goldfarb David S
Published: April 2021

Importin α’s mediate the nuclear transport of many classical nuclear localization signal (cNLS)-containing proteins. Multicellular animals contain multiple importin α genes, most of which fall into three conventional phylogenetic clades, here designated α1, α2, and α3. Using degenerate PCR we cloned Drosophila melanogaster importin α1, α2, and α3 genes, demonstrating that the complete conventional importin α gene family arose prior to the split between invertebrates and vertebrates. We have begun to analyze the genetic interactions among conventional importin α genes by studying their capacity to rescue the male and female sterility of importin α2 null flies. The sterility of α2 null males was rescued to similar extents by importin α1, α2, and α3 transgenes, suggesting that all three conventional importin α’s are capable of performing the important role of importin α2 during spermatogenesis. In contrast, sterility of α2 null females was rescued only by importin α2 transgenes, suggesting that it plays a paralog-specific role in oogenesis. Female infertility was also rescued by a mutant importin α2 transgene lacking a site that is normally phosphorylated in ovaries. These rescue experiments suggest that male and female gametogenesis have distinct requirements for importin α2.
Genetic Control of Cuticle Formation During Embryonic Development ofDrosophila melanogaster
Authors: Ostrowski Stephen , Dierick Herman A , Bejsovec Amy
Published: April 2021

The embryonic cuticle of Drosophila melanogaster is deposited by the epidermal epithelium during stage 16 of development. This tough, waterproof layer is essential for maintaining the structural integrity of the larval body. We have characterized mutations in a set of genes required for proper deposition and/or morphogenesis of the cuticle. Zygotic disruption of any one of these genes results in embryonic lethality. Mutant embryos are hyperactive within the eggshell, resulting in a high proportion reversed within the eggshell (the “retroactive” phenotype), and all show poor cuticle integrity when embryos are mechanically devitellinized. This last property results in embryonic cuticle preparations that appear grossly inflated compared to wild-type cuticles (the “blimp” phenotype). We find that one of these genes, krotzkopf verkehrt (kkv), encodes the Drosophila chitin synthase enzyme and that a closely linked gene, knickkopf (knk), encodes a novel protein that shows genetic interaction with the Drosophila E-cadherin, shotgun. We also demonstrate that two other known mutants, grainy head (grh) and retroactive (rtv), show the blimp phenotype when devitellinized, and we describe a new mutation, called zeppelin (zep), that shows the blimp phenotype but does not produce defects in the head cuticle as the other mutations do.