bluuebunny/crossref_metadata_2025 huggingface dataset:
Closed-Incision Negative-Pressure Wound Therapy after Resection of Soft-Tissue Tumors Reduces Wound Complications: Results of a Randomized Trial
Authors: Dadras Mehran , Ufton Dominic , Sogorski Alexander , Wallner Christoph , Wagner Johannes M. , Lehnhardt Marcus , Harati Kamran , Behr Björn
Published: March 2022

Background:

Wound healing after resection of large soft-tissue tumors is often impaired by large dead space and fluid collection. Recently, the authors were able to show an association of wound complications with worse oncologic outcome in soft-tissue sarcomas. The aim of the study was to examine the value of closed-incision negative pressure wound therapy on postoperative wound drainage and wound complications after soft-tissue tumor resection.

Methods:

Patients for whom resection is planned of a soft-tissue tumor larger than 10 cm in diameter of the extremities or the trunk were allocated randomly to one of two groups. After wound closure, patients in the study group received closed-incision negative-pressure wound therapy for a duration of 5 days, whereas those in the control group received regular dressings. The amount of drainage fluid, course of wound healing, length of hospital stay, and wound edge perfusion at postoperative day 5 measured by white-light infrared spectroscopy were compared.

Results:

Sixty patients could be included in the study with even distribution to both study arms, meeting the goal. The postoperative course of wound drainage volume was significantly lower in the study group, and hospital stay was significantly shorter, with 9.1 ± 3.8 days versus 13.9 ± 11.8 days. The occurrence of wound complications was significantly lower in the study group on time-to-event analysis (one versus six). Tissue spectroscopy revealed a significantly higher oxygen saturation increase in the wound edge for the study group versus the control group.

Conclusion:

Closed-incision negative-pressure wound therapy should be considered for patients undergoing resection of large soft-tissue tumors.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, II.
The Multiple-U Technique: A Novel Microvascular Anastomosis Technique That Guarantees Everted Anastomosis Sites with Solid Intima-to-Intima Contact
Authors: Kuo Spencer Chia-Hao , Tsai Yueh-Ju , Kuo Pao-Jen , Huang Faye , Lin Tsan-Shiun , Hsieh Ching-Hua
Published: March 2022

The key to successful microvascular anastomosis is achieving intima-to-intima contact, which is not always easy. In this article, the authors propose the multiple-U technique, which is a novel microvascular anastomosis technique that characterizes easy and reliable intima-to-intima contact. The technique was performed on patients who underwent free flap reconstruction for head and neck defects at the Kaohsiung Chang Gung Memorial Hospital from September 1, 2020, to November 30, 2020. The immediate patency test results for all vessel anastomoses were positive, and the postoperative recovery courses of the patients were without any vascular complications. In conclusion, the multiple-U technique is a widely available technique that guarantees everted anastomosis sites and solid intima-to-intima contact. This technique can be performed on both arterial and venous anastomoses regardless of vessel size and wall thickness.
Sharing the Operating Room: A Descriptive Study of Combined and Collaborative Plastic Surgery Cases
Authors: Davis Matthew J. , Lopez Joseph P. , Turner Acara , Abu-Ghname Amjed , Davies Lesley W. , Buchanan Edward P.
Published: March 2022

Background:

Plastic surgeons are often asked for intraoperative assistance by other surgical services. Improvement of a plastic surgery service has been shown to improve patient outcomes, decrease length of stay, and increase hospital revenue, yet plastic surgery’s contribution to a hospital tends to be undervalued. The purpose of this study was to quantify the multidisciplinary role the plastic surgery service plays within a single, large pediatric institution.

Methods:

Surgical cases involving both plastic surgery and at least one other team were identified from 2016 to 2019. Each case was categorized as either “combined” or “collaborative” based on whether the two teams worked separately on separate problems or together on the same problem, respectively. Data points collected included combined and collaborative cases, operating room hours, and total hospital charges billed.

Results:

Of the 7564 total plastic surgery cases performed, multidisciplinary cases made up a minority of total cases (16 percent) but required 32 percent of the operating room hours and provided 49 percent of the total charges billed. Collaborative cases alone accounted for 20 percent of the service’s operating room hours and 39 percent of total charges billed, while making up only 8 percent of total cases.

Conclusions:

Relative to cases where plastic surgery operates alone, combined and collaborative cases account for a disproportionately high number of operating room hours and provide a disproportionately high amount of charges billed.
Sublingual Gland Observed on Salivary Gland Scan
Authors: Jung Ju-Yang , Yoon Joon-Kee , Lee Su Jin , An Young-Sil
Published: March 2022

The major salivary glands, namely, the parotid, submandibular, and sublingual glands, are important in maintaining oral cavity health. A salivary gland scan is used to evaluate the uptake and excretory function of the salivary glands. By intravenously injecting 99mTcO4
−, which is distributed like chloride ions in the body, the glands become visible on the salivary gland scan. The parotid and submandibular glands are typically appreciated on the salivary gland scan, but the sublingual gland is not. We present a rare image of a prominent sublingual gland on a salivary gland scan.
The Evolution of Colloid Administration in Burn Resuscitation
Authors: Fidler Philip , Lineaweaver William
Published: March 2022

Colloid administration in acute resuscitation of burn injuries is being increasingly recognized as an important part of fluid management for these injuries. Such clinical experience, along with possibilities of endothelial preservation by colloid solutions, could lead to a major reconsideration of early colloid administration in burn resuscitation.
Genomic Epidemiology of SARS-CoV-2 in Seychelles, 2020-2021
Authors: Morobe John Mwita , Pool Brigitte , Marie Lina , Didon Dwayne , Lambisia Arnold W. , Makori Timothy , Mohammed Khadija Said , de Laurent Zaydah R. , Ndwiga Leonard , Mburu Maureen W. , Moraa Edidah , Murunga Nickson , Musyoki Jennifer , Mwacharo Jedida , Nyamako Lydia , Riako Debra , Ephnatus Pariken , Gambo Faith , Naimani Josephine , Namulondo Joyce , Tembo Susan Zimba , Ogendi Edwin , Balde Thierno , Dratibi Fred Athanasius , Ahmed Yahaya Ali , Gumede Nicksy , Achilla Rachel A. , Borus Peter K. , Wanjohi Dorcas , Tessema Sofonias K. , Mwangangi Joseph , Bejon Philip , Nokes D. James , Ochola-Oyier Lynette Isabella , Githinji George , Biscornet Leon , Agoti Charles N.
Published: March 2022

Seychelles, an archipelago of 155 islands in the Indian Ocean, had confirmed 24,788 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the 31st December 2021. The first SARS-CoV-2 cases in Seychelles were reported on the 14th of March 2020, but cases remained low until January 2021, when a surge of SARS-CoV-2 cases was observed on the islands. Here, we investigated the potential drivers of the surge by genomic analysis 1,056 SARS-CoV-2 positive samples collected in Seychelles between 14th March 2020 and 31st December 2021. The Seychelles genomes were classified into 32 Pango lineages, 1,042 of which fell within four variants of concern i.e., Alpha, Beta, Delta and Omicron. Sporadic cases of SARS-CoV-2 detected in Seychelles in 2020 were mainly of lineage B.1 (European origin) but this lineage was rapidly replaced by Beta variant starting January 2021, and which was also subsequently replaced by the Delta variant in May 2021 that dominated till November 2021 when Omicron cases were identified. Using ancestral state reconstruction approach, we estimated at least 78 independent SARS-CoV-2 introduction events into Seychelles during the study period. Majority of viral introductions into Seychelles occurred in 2021, despite substantial COVID-19 restrictions in place during this period. We conclude that the surge of SARS-CoV-2 cases in Seychelles in January 2021 was primarily due to the introduction of more transmissible SARS-CoV-2 variants into the islands.
Large scale brain network dynamics in very preterm children and relationship with socio-emotional outcomes
Authors: Siffredi Vanessa , Liverani Maria Chiara , Freitas Lorena G. A. , Tadros D. , Farouj Y. , Tolsa Cristina Borradori , Van De Ville Dimitri , Hüppi Petra Susan , Hà-Vinh Leuchter Russia
Published: March 2022

Children born very preterm (VPT; < 32 completed weeks of gestation) are at high risk of neurodevelopmental and neurobehavioral difficulties associated with atypical brain maturation. The analysis of large-scale brain network dynamics during rest allows to investigate brain functional connectivity and their association with behavioural outcomes. Of interest, prematurity has been associated with atypical socio-emotional development with significant implications for the forming of peer relationships, adaptive functioning, academic achievement and mental health. In this study, we extracted dynamic functional connectivity by using the innovation-driven co-activation patterns (iCAPs) framework in preterm and full-term children aged 6 to 9 to explore changes in spatial organisation, laterality and temporal dynamics of spontaneous large-scale brain activity. Multivariate pattern analysis was used to explore potential biomarkers for socio-emotional difficulties in preterm children. Results show a spatial organisation of 13 networks retrieved comparable to full-term controls. Dynamic features and lateralisation of network brain activity were also comparable across groups for all large-scale brain networks. Despite apparent similarities in terms of dynamical functional connectivity parameters, multivariate pattern analysis unveiled group differences in their associations with socio-emotional abilities. While a pattern of decreased engagement in certain brain networks were associated with better socio-emotional abilities in full-term controls; in the VPT group, better socio-emotional abilities were associated with coordination of activity across different networks, i.e., coupling duration between different pairs of networks. It is possible that group differences reflect reduced degree of maturation of functional architecture in the VPT group for socio-emotional abilities.
Mechanistic modeling-guided optimization of microneedle-based skin patch for rapid transdermal delivery of naloxone for opioid overdose treatment
Authors: Tijani Akeemat , Dogra Prashant , Peláez Maria J. , Wang Zhihui , Cristini Vittorio , Puri Ashana
Published: March 2022

Naloxone, an FDA approved opioid inhibitor, used to reverse opioid overdose complications has up till date faced challenges associated with its delivery. Limitations include the use of invasive delivery forms and the need for frequent redosing due to its short half-life. Further, the use of the non-invasive commercially available intranasal form is faced with limitations such as nasal epistaxis and inability to use the intranasal channel due to nasal trauma common in addicts from frequent drug snorting. The goal of the current study was to design a rapidly dissolving polymeric microneedle (MN) patch with delivery and pharmacokinetic properties comparable to that seen with the commercially available NAL products, eliminating their highlighted limitations. Factors such as drug loading and polymer strength influenced the fabrication of the MNs. Compared to passive permeation, a reduced lag time of about 5-15 min was observed with a significant drug flux of 15.09 ± 7.68 μg/cm2/h seen in the first 1 h (p<0.05) with an array of 100 needles (500 µm long). Increasing the MN length and density (no. of needles/unit area) made a significant difference in the amount permeated and flux (p<0.05), with latter being more influential. Further, through a mechanistic model of drug release from the patch, integrated with pharmacokinetic modeling, we optimized the design of the patch to reproduce in-silico the clinical pharmacokinetics of NAL obtained through commercial intramuscular and intranasal devices. Model simulations and analyses revealed the significance of needle base diameter and needle count in improving systemic pharmacokinetics of NAL.
Numb-associated kinases are required for SARS-CoV-2 infection and are cellular targets for therapy
Authors: Karim Marwah , Saul Sirle , Ghita Luca , Sahoo Malaya Kumar , Ye Chengjin , Bhalla Nishank , Jin Jing , Park Jun-Gyu , Martinez-Gualda Belén , East Michael Patrick , Johnson Gary L. , Pinsky Benjamin A. , Martinez-Sobrido Luis , Asquith Christopher R. M. , Narayanan Aarthi , De Jonghe Steven , Einav Shirit
Published: March 2022

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose serious threats to global health. We previously reported that AAK1, BIKE and GAK, members of the Numb-associated kinase family, control intracellular trafficking of multiple RNA viruses during viral entry and assembly/egress. Here, using both genetic and pharmacological approaches, we probe the functional relevance of NAKs for SARS-CoV-2 infection. siRNA-mediated depletion of AAK1, BIKE, GAK, and STK16, the fourth member of the NAK family, suppressed SARS-CoV-2 infection in human lung epithelial cells. Both known and novel small molecules with potent AAK1/BIKE, GAK or STK16 activity suppressed SARS-CoV-2 infection. Moreover, combination treatment with the approved anti-cancer drugs, sunitinib and erlotinib, with potent anti-AAK1/BIKE and GAK activity, respectively, demonstrated synergistic effect against SARS-CoV-2 infection in vitro. Time-of-addition experiments revealed that pharmacological inhibition of AAK1 and BIKE suppressed viral entry as well as late stages of the SARS-CoV-2 life cycle. Lastly, suppression of NAKs expression by siRNAs inhibited entry of both wild type and SARS-CoV-2 pseudovirus. These findings provide insight into the roles of NAKs in SARS-CoV-2 infection and establish a proof-of-principle that pharmacological inhibition of NAKs can be potentially used as a host-targeted approach to treat SARS-CoV-2 with potential implications to other coronaviruses.
High neutralizing antibody levels against SARS-CoV-2 Omicron BA.1 and BA.2 after UB-612 vaccine booster
Authors: Guirakhoo Farshad , Wang Shixia , Wang Chang Yi , Kuo Hui-Kai , Peng Wen-Jiun , Liu Hope , Wang Lixia , Johnson Marina , Hunt Adam , Hu Mei Mei , Monath Thomas P. , Rumyantsev Alexander , Goldblatt David
Published: March 2022

The highly transmissible Omicron variant has caused high rates of breakthrough infections among vaccinated and convalescent individuals. Here, we demonstrate that a booster dose of UB-612 vaccine candidate delivered 7-9 months after primary vaccination increases neutralizing antibody levels by 131-, 61- and 49-fold against ancestral SARS-CoV-2, Omicron BA.1 and BA.2 variants, respectively. Based on the RBD protein binding antibody responses, we estimated a ∼95% efficacy against symptomatic COVID-19 caused by the ancestral strain after a UB-612 booster. Our results support UB-612 vaccine as a potent booster against current and emerging SARS-CoV-2 variants.
IL-27 skews TNF-alpha-induced inflammatory microenvironment in keratinocytes
Authors: Aioi Akihiro , Imamichi Tomozumi
Published: March 2022

Inflammaging has received considerable attention because aging is characterized by low-grade, chronic and asymptomatic inflammation, concomitant with increased blood levels of senescence-associated secretory phenotype (SASP) factors, including IL-1, IL-6, IL-8, IL-18 and tumor necrosis factor-alpha (TNF-alpha). On the other hand, IL-27 is not categorized as SASP factors though it is known that IL-27 has pleiotropic roles in inflammation. Here, we evaluated the interaction between TNF-alpha and IL-27 in the context of low-grade inflammation by using in HaCaT cells. TNF-alpha induced significant upregulation of IL-6 and IL-8 through the experimental concentrations (~10 ng/ml) of TNF-alpha, while the mRNA expression levels of IL-1RA, IL-10 and IL-18BP were unchanged. After confirming the expression of IL-27 receptor in HaCaT cells, we examined the effects of IL-27 alone on the cytokine expression. IL-27 alone significantly enhanced mRNA expression levels of IL-10 and IL-18BP by 1.61-fold and 1.46-fold, respectively, and also enhanced mRNA expression levels of IL-6 by 2.32-fold. In the presence of 100 ng/ml IL-27, the expression levels of anti-inflammatory cytokines, IL-1RA, IL-10 and IL-18BP, were significantly upregulated with the treatment of a physiological concentration (1 ng/ml) TNF-alpha. Taken together, a high concentration of IL-27 exhibits anti-inflammatory effects in the presence of a low concentration of TNF-alpha when keratinocytes are the recipient of IL-27 signaling, suggesting the anti-inflammatory roles of IL-27 in inflammaging may be regulated by TNF-alpha concentration.
A dataset of 5 million city trees: species clustering and climate effects in urban forests
Authors: McCoy Dakota E. , Goulet-Scott Benjamin , Meng Weilin , Atahan Bulent Furkan , Kiros Hana , Nishino Misako , Kartesz John
Published: March 2022

Sustainable cities depend on urban forests. City trees improve our health, clean the air, store CO2, and cool local temperatures. Comparatively less is known about urban forests as ecosystems, particularly their spatial composition, nativity statuses, biodiversity, and tree health. Here, we assembled and standardized a new dataset of N=5,132,890 trees from 63 of the largest US cities with detailed information on location, health, nativity status, and species. We further designed new tools to analyze the ecosystem structure of urban forests, including spatial clustering and abundance of native trees, and validate these tools in comparison to past methods. We show that city trees are significantly clustered by species in 93% of cities, potentially increasing pest vulnerability (even in cities with biodiverse urban forests). Further, non-native species significantly homogenize urban forests across cities, while native trees comprise 0.44%-85.6% (median=45.6%) of city tree populations. Native trees are less frequent in drier cities, and indeed climate significantly shapes both nativity and biodiversity in urban forests. Parks are more biodiverse than urban settings. Compared to past work which focused primarily on canopy cover and species richness, we show the importance of analyzing spatial composition and nativity statuses in urban forests (and we created new datasets and tools to do so). This dataset could be analyzed in combination with citizen-science datasets on bird, insect, or plant biodiversity; social and demographic data; or data on the physical environment. Urban forests offer a rare opportunity to intentionally design biodiverse, heterogenous, rich ecosystems.
Stability-instability transition in tripartite merged ecological networks
Authors: Emary Clive , Malchow Anne-Kathleen
Published: March 2022

Although ecological networks are typically constructed based on a single type of interaction, e.g. trophic interactions in a food web, a more complete picture of ecosystem composition and functioning arises from merging networks of multiple interaction types. In this work, we consider tripartite networks constructed by merging two bipartite networks, one mutualistic and one antagonistic. Taking the interactions within each sub-network to be distributed randomly, we consider the stability of the dynamics of the network based on the spectrum of its community matrix. In the asymptotic limit of a large number of species, we show that the spectrum undergoes an eigenvalue phase transition, which leads to an abrupt destabilisation of the network as the ratio of mutualists to antagonists is increased. We also derive results that show how this transition is manifest in networks of finite size, as well as when disorder is introduced in the segregation of the two interaction types. Our random-matrix results will serve as a baseline for understanding the behaviour of merged networks with more realistic structures and/or more detailed dynamics.
In vivolow-intensity magnetic pulses durably alter neocortical neuron excitability and spontaneous activity
Authors: Boyer Manon , Baudin Paul , Stengel Chloé , Valero-Cabre Antoni , Lohof Ann M. , Charpier Stéphane , Sherrard Rachel M. , Mahon Séverine
Published: March 2022

Magnetic brain stimulation is a promising treatment for neurological and psychiatric disorders. However, a better understanding of its effects at the individual neuron level is essential to improve its clinical application. We combined focal low-intensity repetitive transcranial magnetic stimulation (LI-rTMS) to the rat somatosensory cortex with intracellular recordings of subjacent pyramidal neuronsin vivo. Continuous 10 Hz LI-rTMS reliably evoked firing at ∼4-5 Hz during the stimulation period and induced durable attenuation of synaptic activity and spontaneous firing in cortical neurons, through membrane hyperpolarization and a reduced intrinsic excitability. However, inducing firing in individual neurons by repeated intracellular current injection did not reproduce LI-rTMS effects on neuronal properties. These data provide novel understanding of mechanisms underlying magnetic brain stimulation showing that, in addition to inducing biochemical plasticity, even weak magnetic fields can activate neurons and enduringly modulate their excitability.
Engineering Antioxidant and Oxygen-Releasing Lignin Composites to Promote Wound Healing
Authors: Balaji Swathi , Short Walker D. , Padon Benjamin W. , Belgodere Jorge A. , Jimenez Sarah E. , Deoli Naresh T. , Guidry Anna C. , Green Justin C. , Prajapati Tanuj J. , Farouk Fayiz , Kaul Aditya , Son Dongwan , Jung Olivia S. , Astete Carlos E. , Kim Myungwoong , Jung Jangwook P.
Published: March 2022

The application of engineered biomaterials for wound healing has been pursued since the beginning of tissue engineering. Here, we attempt to apply functionalized lignin to confer antioxidation to the extracellular microenvironments of wounds and to deliver oxygen from the dissociation of calcium peroxide for enhanced vascularization and healing responses without eliciting inflammatory responses. Elemental analysis showed 17 times higher quantity of calcium in the oxygen releasing nanoparticles. Lignin composites including the oxygen releasing nanoparticles released around 500 ppm oxygen per day at least for 7 days. By modulating the concentration of the methacrylated gelatin, we were able to maintain the injectability of lignin composite precursors and the stiffness of lignin composites suitable for wound healing after photo-crosslinking.In situformation of lignin composites with the oxygen releasing nanoparticles enhanced the rate of tissue granulation, the formation of blood vessels and the infiltration of α-smooth muscle actin+fibroblasts into the wounds over 7 days. At 30 days after surgery, the lignin composite with oxygen generating nanoparticles remodeled the collagen architecture resembling to the reticular pattern of unwounded collagen with minimal scar formation. Thus, our study shows the potential of functionalized lignin for wound healing applications requiring balanced antioxidation and controlled release of oxygen for enhanced tissue granulation, vascularization and maturation of collagens.
Hybrid conferences: opportunities, challenges and ways forward
Authors: Puccinelli Eleonora , Zeppilli Daniela , Stefanoudis Paris , Wittische-Helou Annaïg , Kermorgant Marjorie , Fuchs Sandra , Sarrazin Jozée , Easton Erin E. , Weber Alexandra Anh-Thu
Published: March 2022

Hybrid conferences are in-person events that are also accessible online. This type of meeting format was rare pre-COVID-19 but started to become more common recently given the asynchronous global progression of the pandemic and the uneven access and distribution of vaccines that led to a large proportion of participants being unable to attend international conferences in person. Here we report the organization of a middle-sized (581 participants: 159 onsite, 422 online) international hybrid conference that took place in France in September 2021. We highlight particular organizational challenges inherent to this relatively new type of meeting format. Furthermore, we surveyed both in-person and online participants to better understand their conference experience and to propose improvements based on the feedback received. Finally, we compare the advantages and disadvantages of three types of conferences (onsite-only, online-only and hybrid) and suggest that hybrid events should be favored in the future because they offer the most flexibility to participants. We conclude by proposing suggestions and ways forward to maximize accessibility and inclusivity of hybrid conferences.
Barrel cortex development lacks a key stage of hyperconnectivity from deep to superficial layers in a rat model of Absence Epilepsy
Authors: Plutino Simona , Laghouati Emel , Jarre Guillaume , Depaulis Antoine , Guillemain Isabelle , Bureau Ingrid
Published: March 2022

The development of cortical neuronal wiring is precisely orchestrated and goes through several stages, some of which coincide with critical periods when sensory experience is most influential. In particular, although ascending excitatory and inhibitory projections from the deep layer 5 to upper layers are first strong, they recede by the end of the critical period of their targets cells located in upper layers. Alterations in these transient innervations impair the construction of the later circuits that remain at adulthood, but it is unknown whether they could lead to pathologies. Here, we address this question in a genetic model of Absence Epilepsy, a neuro-developmental disease, where epileptogenesis occurs during the postnatal maturation of barrel cortex, the seizure initiation site. Using functional mapping by laser scanning photostimulation with glutamate uncaging in slices, we investigated the pattern of projections onto layers 2/3 pyramidal cells from 2-week old rats. We found that its maturation skipped the key stage during which pyramidal cells received strong projections from both excitatory and inhibitory neurons located in deep layers. At the same age, neuronal activity recorded in vivo with two-photon functional imaging was organized in fewer clusters than in control rat pups during this transient hyper-innervation. Later, around the onset of typical absence seizures (∼1 month old), over-excitability of cells was observed across layers. Using this genetic model of childhood epilepsy, we provide first evidence that failure to develop this transient hyper-innervation from deep cortical layers plays a role in pathological neural dysfunctions.

Significance Statement

During development of cortex, innervation from deep to upper layers is thought to provide a temporary scaffold for the construction of the circuits that remain at adulthood. Whether an alteration in this sequence causes brain malfunctions in neuro-developmental diseases is unknown. Using functional approaches, we investigated in a genetic model of Absence Epilepsy and control rats the maturation of innervation onto layer 2/3 pyramidal cells of barrel cortex and the cell organization into neuronal assemblies. We found that development in this model lacks this early surge of connectivity with deep layers and the concomitant structuring into multiple assemblies. Later on, at seizure onset, neurons in all layers are hyper-excitable, suggesting this feature of epilepsy develops from prior connectivity defects.
Near telomere-to-telomere nuclear phased chromosomes of the dikaryotic wheat fungus Rhizoctonia cerealis
Authors: Zeng Qingdong , Cao Wenjin , Li Wei , Wu Jianhui , Figueroa Melania , Liu Huiquan , Qin Guowei , Wang Qinhu , Yang Liming , Zhou Yan , Yu Yunxin , Huang Lin , Liu Shengjie , Luo Yuming , Mu Zhiying , Li Xiang , Liu Jiajie , Wang Xiaoting , Wang Changfa , Yuan Fengping , Chen Huaigu , Xu Haibin , Dodds Peter N. , Han Dejun , Kang Zhensheng
Published: March 2022

Rhizoctonia cerealis (Rce), which causes sharp eyespot, is one of the most destructive wheat pathogens. However, the genetic and molecular virulence mechanisms of Rce have not been elucidated. As a dikaryotic organism, the haplotype phasing of this fungus has not been completed so far. We applied a haplotype phasing algorithm to generate a high-quality near telomere-to-telomere nuclear-phased genome sequence of Rce strain R0301. Sixteen pairs of chromosomes were assigned to the A and B genomes with a total size of 83 Mb. Based on a dual-time course RNA-seq, 25308 genes were predicted. Genes for steroid biosynthesis and starch and sucrose metabolism were significantly enriched, together with many genes encoding carbohydrate-active enzymes (CAZymes) and secreted effector proteins, which should be involved in infection of wheat plants. Population genomic analysis of 31 isolates collected in China during the last forty years suggests that this population has not undergone substantial differentiation over time.

Importance

The finished genome reference is the basis of revealing pathogens’ biology base. Many efforts have been made to produce the chromosome-scale assembly of fungi. However, the reference of many pathogenic fungi is highly fragmented, which prevents the analysis of genome structure variation, evolution and import pathogenicity genes. Here, we assembly the only chromosome-scale haplotype-phased reference of dikaryotic fungus so far. This assembly achieves the gold standard based on many evaluation software, which indicates that the pipeline developed in this study can be applied to assemble references for other dikaryotic organisms. This work can also promote the research on the globe’s destructive wheat pathogens, sharp eyespot, caused by R. cerealis.
Decoding face recognition abilities in the human brain
Authors: Faghel-Soubeyrand Simon , Ramon Meike , Bamps Eva , Zoia Matteo , Woodhams Jessica , Richoz Anne-Raphaelle , Caldara Roberto , Gosselin Frédéric , Charest Ian
Published: March 2022

Why are some individuals better at recognising faces? Uncovering the neural mechanisms supporting face recognition ability has proven elusive. To tackle this challenge, we used a multi-modal data-driven approach combining neuroimaging, computational modelling, and behavioural tests. We recorded the high-density electroencephalographic brain activity of individuals with extraordinary face recognition abilities—super-recognisers—and typical recognisers in response to diverse visual stimuli. Using multivariate pattern analyses, we decoded face recognition abilities from 1 second of brain activity with up to 80% accuracy. To better understand the mechanisms subtending this decoding, we compared computations in the brains of our participants with those in artificial neural network models of vision and semantics, as well as with those involved in human judgments of shape and meaning similarity. Compared to typical recognisers, we found stronger associations between early brain computations of super-recognisers and mid-level computations of vision models as well as shape similarity judgments. Moreover, we found stronger associations between late brain representations of super-recognisers and computations of the artificial semantic model as well as meaning similarity judgments. Overall, these results indicate that important individual variations in brain processing, including neural computations extending beyond purely visual processes, support differences in face recognition abilities. They provide the first empirical evidence for an association between semantic computations and face recognition abilities. We believe that such multi-modal data-driven approaches will likely play a critical role in further revealing the complex nature of idiosyncratic face recognition in the human brain.

Significance

The ability to robustly recognise faces is crucial to our success as social beings. Yet, we still know little about the brain mechanisms allowing some individuals to excel at face recognition. This study builds on a sizeable neural dataset measuring the brain activity of individuals with extraordinary face recognition abilities—super-recognisers—to tackle this challenge. Using state-of-the-art computational methods, we show robust prediction of face recognition abilities in single individuals from a mere second of brain activity, and revealed specific brain computations supporting individual differences in face recognition ability. Doing so, we provide direct empirical evidence for an association between semantic computations and face recognition abilities in the human brain—a key component of prominent face recognition models.
Unsupervised approach to decomposing neural tuning variability
Authors: Zhu Rong , Wei Xue-Xin
Published: March 2022

Neural representation is often described by the tuning curves of individual neurons with respect to certain stimulus variables. Despite this tradition, it has become increasingly clear that neural tuning can vary substantially in accordance with a collection of internal and external factors. A challenge we are facing is the lack of appropriate methods to accurately capture trial-to-trial tuning variability directly from the noisy neural responses. Here we introduce an unsupervised statistical approach, Poisson functional principal component analysis (Pf-PCA), which identifies different sources of systematic tuning fluctuations, moreover encompassing several current models (e.g.,multiplicative gain models) as special cases. Applying this method to neural data recorded from macaque primary visual cortex– a paradigmatic case for which the tuning curve approach has been scientific essential– we discovered a novel simple relationship governing the variability of orientation tuning, which unifies different types of gain changes proposed previously. By decomposing the neural tuning variability into interpretable components, our method enables discovery of new structure of the neural code, capturing the influence of the stimulus drive and internal states simultaneously.
Exploiting deep transfer learning for the prediction of functional noncoding variants using genomic sequence
Authors: Chen Li , Wang Ye
Published: March 2022

Motivation

Though genome-wide association studies have identified tens of thousands of variants associated with complex traits and most of them fall within the noncoding regions, they may not the causal ones. The development of high-throughput functional assays leads to the discovery of experimental validated noncoding functional variants. However, these validated variants are rare due to technical difficulty and financial cost. The small sample size of validated variants makes it less reliable to develop a supervised machine learning model for achieving a whole genome-wide prediction of noncoding causal variants.

Results

We will exploit a deep transfer learning model, which is based on convolutional neural network, to improve the prediction for functional noncoding variants. To address the challenge of small sample size, the transfer learning model leverages both large-scale generic functional noncoding variants to improve the learning of low-level features and context-specific functional noncoding variants to learn high-level features toward the contextspecific prediction task. By evaluating the deep transfer learning model on three MPRA datasets and 16 GWAS datasets, we demonstrate that the proposed model outperforms deep learning models without pretraining or retraining. In addition, the deep transfer learning model outperforms 18 existing computational methods in both MPRA and GWAS datasets.

Availability

https://github.com/lichen-lab/TLVar

Supplementary Information

Supplementary data are available at Bioinformatics online.

Contact

chen61@iu.edu
Environmental and genetic disease modifiers of haploinsufficiency of A20
Authors: Zammit Nathan W. , Gray Paul E. , Siggs Owen M. , Yap Jin Yan , Russell Amanda , Cultrone Daniele , Warren Joanna , Walters Stacey N. , Brink Robert , Zahra David , Burnett Deborah L. , Gayevskiy Velimir , Minoche Andre E. , Ziegler John B. , Craig Maria E. , Wong Melanie , Benitez-Aguirre Paul , Teo Juliana , Cowley Mark J. , Dinger Marcel E. , Tangye Stuart G. , Burke Catherine , Phan Tri G. , Goodnow Christopher C. , Grey Shane T.
Published: March 2022

Monogenic diseases can often manifest diverse clinical phenotypes and cause diagnostic dilemmas. While monoallelic loss-of-function variants in TNFAIP3 (Haploinsufficiency of A20; HA20) cause a highly penetrant autoinflammatory disease, the variable expressivity suggest a role for additional genetic and environmental disease modifiers. Here, we identify critically ill children who inherited a family-specific TNFAIP3 deletion from one of their otherwise healthy parents. Each of the probands also inherited in trans a subtle loss-of-function I207L TNFAIP3 variant that is common in Oceania, originally introgressed from Denisovans. Modelling this compound heterozgous state in mice under specific pathogen free conditions demonstrated a reduced threshold to break immune tolerance. Exaggerated immune responses were precipitated by inheriting the two genetic hits on the TNFAIP3 checkpoint coupled with increasing the microbial challenge to immune tolerance, either by co-housing with pet store mice carrying a wild microbial burden or by transient dietary exposure to a chemical that diminishes the intestinal mucin barrier separating gut microbes from immune sensing systems. These data illuminate second-hit genetic and environmental modifiers contributing to complex inflammatory and autoimmune disease. Increased mechanistic understanding of the presence and contribution of disease modifiers will aid diagnostic and prognostic patient stratification and potentially reveal novel therapeutic opportunities.
A Cambrian soft-bodied conical animal illustrates the origins of lophophorate phyla
Authors: Zeng Han , Chen Xiangyuan , Liu Yao , Zhu Maoyan , Zhao Fangchen , Yang Aihua
Published: March 2022

The origin and early evolution of lophotrochozoans remain a difficult but crucial issue in reconstructing metazoan phylogeny. Exceptionally preserved fossils have provided hopeful information for resolving this lophotrochozoan problem. Here we identify that Conicula striata, a soft-bodied conical animal from the early Cambrian Chengjiang Lagerstätte, has mosaic characteristics of different lophophorate phyla. C. striata possesses a phoronid-like vermiform trunk housing a U-shaped gut and a coiled lophophore comprising ≥12 arms with numerous tentacles, but it also bears brachiopod-like features including an undivided mantle enclosing lophophore and a pedicle-like protrusion on annulated trunk. Phylogenetic analysis retrieves C. striata as a total-group lophophorate and as an intermediate taxon between Phoronida and Brachiopoda. This suggests that the bivalved architecture of brachiopods originated from an undivided mantle in a phoronid-like ancestor, and that the ancestral vermiform trunk became reduced during the origin of Brachiopoda, illuminating the origins of body plans in the lophophorate phyla.
SER: an R package to compute environmental regime over a certain time period
Authors: Wu Naicheng , Guo Kun , Zou Yi , He Fengzhi , Riis Tenna
Published: March 2022

Environmental regime (or environmental legacy or historical legacy) is the environmental dynamic characteristics over a given (either long or short) time period, such as frequency of mean or extreme events and rate of change, which might be masked by using only contemporary variables.

We present SER, an R package for estimating environmental regimes for different environmental variables. Using the data included in the package, several examples are shown.

SER is suitable for any types of environmental variables e.g., nutrient concentration, light, dissolved oxygen. In addition, by changing the argument “days_bf”, it is possible to compute environmental regimes in any interested time period, such as days, months or years.

Our case study showed that inclusion of environmental regimes dramatically increased the explained variation of temporal β-diversity and its components. Environmental regimes, particularly in a given time period, are expected to advance the “environment - community” relationships in ecological studies. In addition, they can be implemented in other subjects, e.g., social science, socioeconomics, epidemiology, with important applied implications.
Epidemiology and medical costs of orthopedic conditions in a tertiary hospital in Kenya; A five-year analysis of admission data
Authors: Kihuba Elesban
Published: March 2022

Background

Orthopedic services are a key component of the surgical healthcare system. Scaling up these services would not only reduce the musculoskeletal diseases burden but also the overall disease burden significantly. As such quality intelligence on epidemiology and costs of orthopedic services should be accurately represented for guiding effective policy formulation and implementation.

Aim

The aim of the study was to provide a snapshot of the pattern of orthopedic admissions, care and associated medical costs in Kenya.

Methods

A retrospective study was conducted reviewing case files of patients admitted to the orthopedic department from 1st January 2015 to 30st November 2019.

Results

There were 4320 distinct musculoskeletal admission diagnoses among the 3527 admissions. The study shows that trauma accounts for 53.04% of all admissions while joint replacement, shoulder and knee, limb deformities, infection, removal of hardware, ankle and foot and tumour procedures accounts for 15.01%, 8.87%, 7.29%, 6.44%, 3.94% and 3.23% respectively. Joint replacement is the leading diagnosis among patients in the 61 to 75 years age group and fragility fractures and posttraumatic arthritis featured prominently as the key reasons for joint reconstruction. The proportion of admissions with health insurance (60.82%) was exceptionally high compared to the national average (19.59%). However, current financing mechanism provide inadequate social protection against cost of orthopedic surgery.

Conclusion

The case volume and mix highlight the growing importance of trauma, fragility fractures and degenerative joint diseases in orthopedic care in developing country set up. Overall, the observed model of care and associated outcome and costs provide a blueprint for orthopedic system development.
A Systematic Review of Human Challenge Trials, Designs, and Safety
Authors: Adams-Phipps Jupiter , Toomey Danny , Więcek Witold , Schmit Virginia , Wilkinson James , Scholl Keller , Jamrozik Euzebiusz , Osowicki Joshua , Roestenberg Meta , Manheim David
Published: March 2022

Background

There exists no prior systematic review of human challenge trials (HCTs) that focuses on participant safety. Key questions regarding HCTs include how risky such trials have been, how often adverse events (AEs) and serious adverse events (SAEs) occur, and whether risk mitigation measures have been effective.

Methods

A systematic search of PubMed and PubMed Central for articles reporting on results of HCTs published between 1980 and 2021 was performed and completed by 10/7/2021.

Results

Of 2,838 articles screened, 276 were reviewed in full. 15,046 challenged participants were described in 308 studies that met inclusion criteria. 286 (92.9%) of these studies reported mitigation measures used to minimize risk to the challenge population. Among 187 studies which reported on SAEs, 0.2% of participants experienced at least one challenge-related SAE. Among 94 studies that graded AEs by severity, challenge-related AEs graded “severe” were reported by between 5.6% and 15.8% of participants. AE data were provided as a range to account for unclear reporting. 80% of studies published after 2010 were registered in a trials database.

Conclusions

HCTs are increasingly common and used for an expanding list of diseases. Although AEs occur, severe AEs and SAEs are rare. Reporting has improved over time, though not all papers provide a comprehensive report of relevant health impacts. From the available data, most HCTs do not lead to a high number of severe symptoms or SAEs. This study was preregistered on PROSPERO as CRD42021247218.
CMLD-2 Attenuates Myofibroblast Activation and Bleomycin-Induced Pulmonary Fibrosis in Mice through Antagonizing ELAVL1-Mediated Osteopontin mRNA Stabilization
Authors: Qiongya Guo , Hongyan Ren , Meng Li , Lifan Liu , Wenting Li , Jingjing Zhang , Xiaoli Wang , Yiping Hu , Kaixuan Zang , Yunxia An , Lin Li , Li Wei , Zhiwei Xu , Zhiping Guo , Costabel Ulrich , Xiaoju Zhang , Zheng Wang
Published: March 2022

Background

Fibroblast-myofibroblasts transition (FMT) is one of the hallmark cellular processes in pulmonary fibrosis. This study is to investigate the effects of CMLD-2 in FMT and pulmonary fibrosis, which antagonizes HuR, a supposedly key regulatory RNA binding protein (RBP).

Methods

HuR or other deferentially expressed RBPs during TGF-β1-induced FMT were analyzed by transcriptomic methods, and further validatedin vitroor in fibrotic lung specimens. The effects of HuR overexpression, down-regulation or inhibition by an antagonist CMLD-2 were analyzed in FMT or bleomycin-induced experimental lung fibrosis. HuR-targeting RNA and their interactions were analyzed by CLIP-seq.

Results

HuR, hnRNPA1, hnRNPE1, TIA1 and TFRC were significantly up-regulated, while ESRP1, ESRP2 and TTP were significantly down-regulated. Cytoplasmic expression of HuR was activated in IPF lung tissue and rat lungs of bleomycin-induced fibrosis. HuR overexpression induced α-SMA and collagen I expression, increased the proliferation and migration capacities of fibroblasts with or without the stimulation of TGF-β1. HuR knockdown by shRNA inhibited the proliferation, transition, collagen production and migration properties in fibroblasts or in TGF-β1-stimulated myofibroblasts. Combinative analysis of RNA-seq and CLIP-seq data revealed major HuR binding motifs and several HuR-bound, differentially expressed mRNAs in FMT, specifically SPP1 mRNA encoding osteopontin. HuR-mediated SPP1 mRNA stabilization was further validated by RIP-PCR and half-life analysis using SPP1 mutant transcripts. Inhibiting HuR using CMLD-2 attenuated SPP1/osteopontin expression, TGF-β1-induced FMTin vitroand bleomycin-induced pulmonary fibrosis in mice. Nuclear-cytoplasmic shuttle of HuR was activated in TGF-β1-induced FMT, which was inhibited by p38MAPK (SB203580) or PKC (Go-6976) inhibition, but not associated with phosphorylation of HuR.

Conclusions

Fibroblast-myofibroblast transition is activated by HuR-SPP1 mRNA interactions, and CMLD-2 is potentiated to be a therapeutic agent targeting HuR for fibroblast-myofibroblast transition and pulmonary fibrosis.
Short-term and bystander effects of radiation on murine submandibular glands
Authors: Uchida Hitoshi , Ingalls Matthew H. , Maruyama Eri O. , Johnston Carl J. , Hernady Eric , Faustoferri Roberta C. , Ovitt Catherine E.
Published: March 2022

Many patients treated for head and neck cancers experience salivary gland hypofunction due to radiation damage. Understanding the mechanisms of cellular damage induced by radiation treatment is important in order to design methods of radioprotection. In addition, it is crucial to recognize the indirect effects of IR and the systemic responses that may alter saliva secretion. In this study, radiation was delivered to murine submandibular glands (SMG) bilaterally, using a 137Cs gamma ray irradiator, or unilaterally, using a small animal radiation research platform (SARRP). Analysis at 3, 24 and 48 hours showed dynamic changes in mRNA levels and protein abundance in SMG irradiated bilaterally. Unilateral irradiation using the SARRP caused similar changes in the irradiated SMG, as well as significant off-target, bystander effects in the non-irradiated contralateral SMG.

Summary statement

Rapid changes in gene expression occur in irradiated salivary glands within hours of irradiation, and in non-irradiated contralateral glands, due to bystander effects.