bluuebunny/crossref_metadata_2025 huggingface dataset:
Multicenter retrospective analysis of clinicopathological features and prognosis of oral tongue squamous cell carcinoma in adolescent and young adult patients
Authors: Okuyama Kohei , Yanamoto Souichi , Michi Yasuyuki , Shibata Eri , Tsuchiya Maiko , Yokokawa Misaki , Naruse Tomofumi , Tomioka Hirofumi , Kuroshima Takeshi , Shimamoto Hiroaki , Ikeda Tohru , Umeda Masahiro , Yoda Tetsuya , Harada Hiroyuki
Published: November 2021

The aim of this study is to report the differences in clinicopathological features of oral tongue squamous cell carcinoma (OTSCC) and survival between adolescent and young adult (AYA) patients and elderly patients and to find the prognosticators. The medical records of 101 AYA patients and 175 control patients with OTSCC who underwent surgery were reviewed. Variables related to prognosis and their clinicopathological associations were analyzed. The 5-year overall survival (5y-OS) rates of AYA and control patients with stage I and II OTSCC were 94.4% and 89.6% (P = .353), respectively, and their 5-year disease-free survival (5y-DFS) rates were 82.0% and 76.6%, respectively (P = .476). The 5y-OS rates of patients with stages III and IV OTSCC were 83.3% and 66.7% (P = .333), respectively, and their 5y-DFS rates were 75.0% and 57.1% (P = .335), respectively. Logistic regression analysis revealed that there was no significant clinicopathological difference in AYA and control group. Furthermore, there was no significant difference in 5y-OS rates between patients who underwent elective neck dissection (END) and those who underwent therapeutic neck dissection (TND) in both group (P = 0.717 and 0.688). Overall, the present study revealed the clinicopathological features and prognosis of OTSCC were similar in AYA patients and elderly patients. Moreover, as there was no significant difference in OS between patients who underwent END and those who underwent TND in AYA and control groups, our results suggest that the indication for END in AYA patients with clinical N0 OTSCC is similar to that for elderly patients.
Targeting tumor microenvironment and metastasis in children with solid tumors
Authors: Wessel Kristin M. , Kaplan Rosandra N.
Published: November 2021

Purpose of review

The prognosis of pediatric patients with metastatic solid tumors remains poor, necessitating development of novel therapeutic strategies. The biology of the pediatric tumor microenvironment (TME) presents obstacles for the efficacy of current therapeutic approaches including immunotherapies. Targeting various aspects of the TME in pediatric patients with solid tumors represents a therapeutic opportunity that may improve outcomes. Here we will discuss recent advances in characterization of the TME, and clinical advances in targeting the immune, vascular, and stromal aspects of the TME.

Recent findings

Although immunotherapies have shown limited success in the treatment of pediatric solid tumor patients thus far, optimization of these approaches to overcome the TME shows promise. In addition, there is increasing focus on the myeloid compartment as a therapeutic target. Vascular endothelial growth factor (VEGF) targeting has resulted in responses in some refractory pediatric solid tumors. There has been relatively little focus on stromal targeting; however, emerging preclinical data are improving our understanding of underlying biology, paving the way for future therapies.

Although translation of TME-targeting therapies for pediatric solid tumors is in the early stages, we are optimistic that continued exploration of approaches aimed at rebalancing the TME will lead to improved outcomes for this population.
Restaging transurethral resection in ta high-grade nonmuscle invasive bladder cancer: a systematic review
Authors: Regnier Sophie , Califano Gianluigi , Elalouf Vincent , Albisinni Simone , Aziz Atiqullah , Di Trapani Ettore , Krajewski Wojciech , Mari Andrea , D’Andrea David , Pradère Benjamin , Soria Francesco , Afferi Luca , Moschini Marco , Ouzaid Idir , Xylinas Evanguelos
Published: November 2021

Purpose of review

The role of a re-transurethral resection (TUR) is clearly demonstrated in T1 high-grade nonmuscle invasive bladder cancer. However, its role remains controversial for Ta high-risk tumors and the recent European guidelines stated that the second look procedure could be avoided for these patients despite harboring a high-risk of both disease recurrence and progression. We aimed to evaluate the added benefit on staging, response to bacillus Calmette–Guérin and oncological outcomes of re-TUR in patients with Ta high-grade nonmuscle invasive bladder cancer.

Recent findings

Overall, we identified 15 studies, including 3912 patients from which 743 harbored Ta high-grade disease. Delay between first and second TUR was ranging from 2 to 12 weeks (median 5.6 weeks). The rate of residual disease was 52.8% (range 17–67%). The rate of overall upstaging to T1 and muscle-invasive disease were 10.9 and 4.7%, respectively. Although there was a trend toward improvement of recurrence-free survival outcomes, no definitive conclusions can be drawn due to the retrospective design of the studies included.

Residual tumor is common after initial TUR for Ta high-grade. Re-TUR is useful in reducing the rates of residual disease, may improve staging, response to bacillus Calmette–Guérin and oncological outcomes.
New drugs for methicillin-resistant Staphylococcus aureus skin and soft tissue infections
Authors: Hindy Joya-Rita , Haddad Sara F. , Kanj Souha S.
Published: November 2021

Purpose of review

Staphylococcus aureus is a pathogen incriminated in skin and soft tissue infections (SSTIs), with methicillin-resistant S. aureus (MRSA) becoming the predominant cause and representing a significant burden to the healthcare system. The last updated Infectious Diseases Society of America (IDSA) guidelines concerning MRSA infections and SSTIs management were published in 2011 and 2014, respectively. The UK updated guidelines for MRSA infection treatment were published in 2021. Older treatment options may be associated with toxicity and require frequent dosing. There is a paucity of recent reviews on the armamentarium of new agents for MRSA SSTIs treatment.

Recent findings

Since 2005, several new antibiotics received a fast-track approval by the Food and Drug Administration (FDA) for SSTI treatment. These drugs include delafloxacin, omadacycline, tedizolid, ceftaroline, dalbavancin, oritavancin and telavancin. In this manuscript, we will review the data that led to these new drugs approval and discuss their advantages and disadvantages in MRSA SSTIs management.

MRSA is a major cause of SSTIs. Several novel therapies covering MRSA were FDA-approved for SSTIs. However, the current IDSA guidelines for MRSA infection and SSTIs as well as the recently published UK guidelines on MRSA treatment only consider these drugs as alternative choices or do not mention them at all.
Reconstruction of the Meatus Urethrae After Oncologic Vulvectomy
Authors: Lange Maurits , Hage J. Joris , Hartveld Loes , Zijlmans Henry J.M.A.A. , van Beurden Marc
Published: November 2021

Background and Aim

Resection of the distal part of the urethra is performed in 15% to 55% of women with vulvar cancer to achieve radicality of vulvectomy. Urinary reconstruction in these women may be complicated by urethral stenosis resulting from circular inset of the meatus. We report on our experience with 2 surgical techniques of noncircular inset to prevent such stenosis.

Methods

From January 2005 to January 2020, 42 urethral meatus reconstructions were performed in 41 women after vulvectomy for (pre)malignant skin disorders by a “limited” (n = 17) or “extended” (n = 25) anterior vaginal wall advancement technique, including V-Y insertion of part of the vaginal flap in a posterior longitudinal urethrotomy. Preoperative characteristics, procedural details, and surgical outcomes were reviewed.

Results

We observed 1 neomeatal stenosis and 1 case of partial vaginal wall flap necrosis as major complications following the “limited” technique and 1 circumferential neomeatal dehiscence and occlusion as major complication after the “extended” technique. Both the neomeatal stenosis and the dehiscence/occlusion are felt to have been preventable and not caused by a flaw of design of the advancement technique.

Conclusions

We advocate applying these vaginal wall advancement techniques to prevent circular inset of the neomeatus. The “extended” technique offers a solution in cases where the periurethral vulvar defect cannot be closed by transpositioning of labial skin.
Persistent challenges in endovascular treatment decision-making for acute ischaemic stroke
Authors: Fiehler Jens , Nawka Marie Teresa , Meyer Lukas
Published: November 2021

Purpose of review

Although endovascular treatment (EVT) is the gold standard for treating acute stroke patients with large vessel occlusion (LVO), multiple challenges in decision-making for specific conditions persist. Recent evidence on a selection of patient subgroups will be discussed in this narrative review.

Recent findings

Two randomized controlled trials (RCTs) have been published in EVT of basilar artery occlusion (BAO). Large single arm studies showed promising results in Patients with low Alberta stroke program early CT score (ASPECTS) and more distal vessel occlusions. Recent data confirm patients with low National Institutes of Health Stroke Scale (NIHSS) despite LVO to represent a heterogeneous and challenging patient group.

The current evidence does not justify withholding EVT from BAO patients as none of the RCTs showed any signal of superiority of BMT alone vs. EVT. Patients with low ASPECTS, more distal vessel occlusions and patients with low NIHSS scores should be included into RCTs if possible. Without participation in a RCT, patients should be selected for EVT based on age, severity and type of neurological impairment, time since symptom onset, location of the ischaemic lesion and perhaps also results of advanced imaging.
Optic Nerve Abnormalities in Morning Glory Disc Anomaly: An MRI Study
Authors: Nguyen Diem-Trang , Boddaert Nathalie , Bremond-Gignac Dominique , Robert Matthieu P.
Published: November 2021

Background:

The morning glory disc anomaly (MGDA) is a rare congenital malformation of the optic disc. The association with a significant enlargement of the optic nerve has been recently reported in a few cases, raising the question of potentially associated optic nerve gliomas. The objective was to report the anatomy of optic nerves on MRI in patients with MGDA.

Methods:

In this retrospective single-center study, files of patients with a clinical diagnosis of MGDA were identified through a rare disease database (CEMARA) and included. We reviewed every cerebral and orbital MRI available, performed between 2008 and 2018. Anatomy of the optic nerve from the optic disc to the chiasm was evaluated on MRI.

Results:

Nine patients were included. All presented unilateral MGDA. Age at first MRI was 0.6–62 years, median = 3.8 years. MRI showed posterior protrusion of the globe (staphyloma) centered by the optic disc in all cases (100%). Ipsilateral optic nerve abnormalities were found in all cases (100%). The optic nerve was found thinner than the contralateral one in its intraorbital, intracanalar, and intracranial portions in 1 case (11%); in 8 cases (89%), the thickness of the optic nerve was irregular and varied along its pathway: thick, normal, and/or thin. When gadolinium injection had been performed (3 cases), none exhibited gadolinium enhancement. When serial MRI scanning was available (4 cases), there was no evolution of the abnormalities.

Conclusion:

In patients with MGDA, optic nerve and chiasm abnormalities are the rule, with most often a unique pattern of irregular optic nerve thickness—hypertrophy and hypoplasia—from the orbit to the chiasm. Such pattern should be recognized and points to a developmental abnormality, rather than an optic nerve glioma.
Temporal Patterns of Spontaneous Fixational Eye Movements: The Influence of Basal Ganglia
Authors: Beylergil Sinem Balta , Murray Jordan , Noecker Angela M. , Gupta Palak , Kilbane Camilla , McIntyre Cameron C. , Ghasia Fatema F. , Shaikh Aasef G.
Published: November 2021

Background:

Spontaneity is a unique feature of the nervous system. One of the fundamentally critical and recognized forms of spontaneous motor activity is witnessed in the visuomotor system. Microsaccades, the miniature spontaneous eye movements, are critical for the visual perception. We hypothesized that microsaccades follow specific temporal patterns that are modulated by the basal ganglia output.

Methods:

We used high-resolution video-oculography to capture microsaccades in 48 subjects (31 healthy and 17 with Parkinson's disease) when subjects were asked to hold their gaze on a straight-ahead target projected on white background. We analyzed spontaneous discharge patterns of microsaccades.

Results:

The first analysis considering coefficient of variation in intersaccadic interval distribution demonstrated that microsaccades in Parkinson's disease are more dispersed than the control group. The second analysis scrutinized microsaccades' temporal variability and revealed 3 distinct occurrence patterns: regular rhythmic, clustered, and randomly occurring following a Poisson-like process. The regular pattern was relatively more common in Parkinson's disease. Subthalamic DBS modulated this temporal pattern. The amount of change in the temporal variability depended on the DBS-induced volume of tissue activation and its overlap with the subthalamic nucleus. The third analysis determined the autocorrelations of microsaccades within 2-second time windows. We found that Parkinson's disease altered local temporal organization in microsaccade generation, and DBS had a modulatory effect.

Conclusion:

The microsaccades occur in 3 temporal patterns. The basal ganglia are one of the modulators of the microsaccade spontaneity.
Space-time Classification Index for Assessing COVID-19 Hotspots
Authors: Haynes David , Tiwari Chetan
Published: November 2021

Objectives

To develop new methods to address problems associated with use of traditional measures of disease surveillance, including prevalence and positivity rates.

Methods

We use data from the public New York Times Github repository to develop a space-time classification index of COVID-19 hotspots. The Local Indicator of Spatial Association (LISA) statistic is applied to identify daily clusters of COVID-19 cases, from July 4th to July 19th.

Results

The classification index is a spatial and temporal assessment tool that seeks to incorporate temporal trends of the clusters that are “high-high” and “high-low”. Two classifications support the index: severity and temporal duration. We define severity as the number of times a county is statistically significant and temporal duration captures the number of consecutive days a county is a hotspot.

Conclusions

The space-time classification index provides a statistically robust measure of the spatial patterns of COVID-19 hotspots. Spatial information is not captured through measures like the positivity rate, which merely divides the number of cases by tests conducted. The index proposed in this paper can guide intervention efforts by classifying counties with six-levels of importance.
KBG Syndrome: Prospective Videoconferencing and Use of AI-driven Facial Phenotyping in 25 New Patients
Authors: Guo Lily , Park Jiyeon , Yi Edward , Marchi Elaine , Hsieh Tzung-Chien , Kibalnyk Yana , Moreno-Sáez Yolanda , Biskup Saskia , Puk Oliver , Beger Carmela , Voronova Anastassia , Krawitz Peter M. , Lyon Gholson J.
Published: November 2021

Genetic variants in the gene Ankyrin Repeat Domain 11 (ANKRD11) and deletions in 16q24.3 are known to cause KBG syndrome, a rare syndrome associated with craniofacial, intellectual, and neurobehavioral anomalies. We report 25 unpublished individuals from 22 families, all with molecularly confirmed diagnoses of KBG syndrome. Twenty-one individuals have de novo variants, three have inherited variants, and one is inherited from a parent exhibiting low-level mosaicism. Of the variants, 20 are truncating (frameshift or nonsense), and the remaining five individuals have missense variants (with one of these in three family members). One of the missense variants has been found in at least two other affected individuals. We created a novel protocol for collection and reporting of data, including prospectively interviewing these individuals and their families throughout eight countries via videoconferencing by a single clinician. Participants’ medical records, including imaging, were reviewed, and data was uploaded to the Human Disease Gene website using Human Phenotype Ontology (HPO) terms. Photos of the participants were submitted to GestaltMatcher and Face2Gene (FDNA Inc, USA) for facial analysis, and we found similar facial phenotypes among the participants. Within our cohort, common traits included short stature, macrodontia, anteverted nares, wide nasal bridge, wide nasal base, thick eyebrows, synophrys and hypertelorism. Seventy-two percent of participants had gastrointestinal complaints and 80% had hearing loss. Three participants were started on growth hormone with positive results. Behavioral issues and global developmental delays were found in most participants. Neurologic abnormalities including seizures and/or EEG abnormalities were also very common (44%), suggesting that early detection and seizure prophylaxis could be an important point of intervention. Twenty-four percent were diagnosed with attention deficit hyperactivity disorder (ADHD) and 28% were diagnosed with autism spectrum disorder (ASD). Additionally, we have identified minimally reported symptoms, including recurrent sinus infections (16%) and previously unreported migraines (20%). Based on the videoconferencing and these data, we provide a set of recommendations regarding diagnostic and treatment approaches for KBG syndrome.
Efficacy and safety of a novel antiviral preparation in ICU-admitted patients with COVID-19: a phase III randomized controlled trial
Authors: Faramarzi Hossein , Sahebkar Amirhossein , Hosseinpour Ahmad , Khaloo Vahid , Chamanpara Parisa , Heydari Mohammad Reza , Najafi Sajad , Khankahdany Fatemeh Fotoohi , Movahedpour Ahmad
Published: November 2021

Introduction

Despite an increasing number of studies, there is as yet no efficient antiviral treatment developed for the disease. In this clinical trial, we examined the efficacy of a novel herbal antiviral preparation comprising Zataria multiflora Boiss, Glycyrrhiza glabra, Cinnamomum Vermont, Allium sativuml, and Syzygium aromaticum in critically ill patients with COVID-19 patients.

Methods

A total number of 120 ICU-admitted patients requiring pulmonary support with a diagnosis of COVID-19 pneumonia were recruited to the trial. Participants were equally randomized to receive either the novel antiviral preparation sublingually, for up to two consecutive weeks or till discharge, or normal saline as the matching placebo. Clinical and laboratory parameters as well as survival rates were compared between the two groups at the study end.

Results

The cumulative incidence of death throughout the study period was 8.33% in the medication group and 60% in the placebo group (risk ratio: 0.14; 95% confidence interval [CI], 0.05 to 0.32; P<0.001). Survival rates were significantly higher in the treatment group. Additionally, on day 7, several laboratory factors including white blood cells (WBCs) count, C-reactive protein (CRP), and SpO2 were improved in patients treated with the novel antiviral preparation compared with the placebo group.

Conclusion

The novel antiviral preparation tested in this trial significantly improved the survival rate and reduced mortality in critically ill patients with COVID-19. Thus, this preparation might be suggested as a potentially promising COVID-19 treatment.

Funded by Shimi Teb Salamat Co., Shiraz, Iran, and registered on the Iranian registry of clinical trials (registration No. IRCT20200509047373N2).
Airway epithelial interferon response to SARS-CoV-2 is inferior to rhinovirus and heterologous rhinovirus infection suppresses SARS-CoV-2 replication
Authors: Vanderwall Elizabeth R. , Barrow Kaitlyn A. , Rich Lucille M. , Read David F. , Trapnell Cole , Okoloko Oghenemega , Ziegler Steven F. , Hallstrand Teal S. , White Maria P. , Debley Jason S.
Published: November 2021

Introduction

Common alphacoronaviruses and human rhinoviruses (HRV) induce type I and III interferon (IFN) responses important to limiting viral replication in the airway epithelium. In contrast, highly pathogenic betacoronaviruses including SARS-CoV-2 may evade or antagonize RNA-induced IFN I/III responses.

Methods

In airway epithelial cells (AECs) from children and older adults we compared IFN I/III responses to SARS-CoV-2 and HRV-16, and assessed whether pre-infection with HRV-16, or pretreatment with recombinant IFN-β or IFN-λ, modified SARS-CoV-2 replication. Bronchial AECs from children (ages 6-18 yrs.) and older adults (ages 60-75 yrs.) were differentiated ex vivo to generate organotypic cultures. In a biosafety level 3 (BSL-3) facility, cultures were infected with SARS-CoV-2 or HRV-16, and RNA and protein was harvested from cell lysates 96 hrs. following infection and supernatant was collected 48 and 96 hrs. following infection. In additional experiments cultures were pre-infected with HRV-16, or pre-treated with recombinant IFN-β1 or IFN-λ2 before SARS-CoV-2 infection.

Results

Despite significant between-donor heterogeneity SARS-CoV-2 replicated 100 times more efficiently than HRV-16. IFNB1, INFL2, and CXCL10 gene expression and protein production following HRV-16 infection was significantly greater than following SARS-CoV-2. IFN gene expression and protein production were inversely correlated with SARS-CoV-2 replication. Treatment of cultures with recombinant IFNβ1 or IFNλ2, or pre-infection of cultures with HRV-16, markedly reduced SARS-CoV-2 replication.

Discussion

In addition to marked between-donor heterogeneity in IFN responses and viral replication, SARS-CoV-2 elicits a less robust IFN response in primary AEC cultures than does rhinovirus, and heterologous rhinovirus infection, or treatment with recombinant IFN-β1 or IFN-λ2, markedly reduces SARS-CoV-2 replication.
Klebsiella pneumoniae mutants resistant to ceftazidime/avibactam plus aztreonam, imipenem/relebactam, meropenem/vaborbactam and cefepime/taniborbactam
Authors: Satapoomin Naphat , Dulyayangkul Punyawee , Avison Matthew B.
Published: November 2021

Using modified Klebsiella pneumoniae clinical isolates, we show that ramR plus ompK36 mutation together with production of the V239G variant KPC-3 confirs resistance to ceftazidime/avibactam plus aztreonam, imipenem/relebactam and meropenem/vaborbactam, but not cefepime/taniborbactam. This is because the V239G variant does not generate collateral β-lactam susceptibility as do many other KPC-3 variants associated with ceftazidime/avibactam resistance. Additional mutation of ompK35 and carriage of a plasmid expressing the OXA-48-like carbapenemase OXA-232 was required to confer cefepime/taniborbactam resistance.
Patient brain organoids identify a link between the 16p11.2 copy number variant and the RBFOX1 gene
Authors: Kostic Milos , Raymond Joseph J. , Henry Beata , Tumkaya Tayfun , Khlghatyan Jivan , Dvornik Jill , Hsiao Jack S. , Cheon Seon Hye , Chung Jonathan , Sun Yishan , Dolmetsch Ricardo E. , Worringer Kathleen A. , Ihry Robert J.
Published: November 2021

Copy number variants (CNVs) that delete or duplicate 30 genes within the 16p11.2 genomic region give rise to a range of neurodevelopmental phenotypes with high penetrance in humans. Despite the identification of this small region, the mechanisms by which 16p11.2 CNVs lead to disease are unclear. Relevant models, like human cortical organoids (hCOs), are needed to understand the human-specific mechanisms of neurodevelopmental disease. We generated hCOs from 18 patients and controls, profiling 167,958 cells with single cell (sc)RNA-seq. Analysis revealed neuronal-specific differential expression of genes outside of the 16p11.2 region that were related to cell-cell adhesion, neuronal projection growth, and neurodevelopmental disorders. Furthermore, 16p11.2 deletion syndrome organoids exhibited reduced mRNA and protein levels of RBFOX1, a gene which can also harbor CNVs linked to neurodevelopmental phenotypes. We found that many genes previously shown to be regulated by RBFOX1 are also perturbed in organoids from patients with 16p11.2 deletion syndrome, and thus identified a novel link between independent CNVs associated with neuronal development and autism. Overall, this work suggests convergent signaling, which indicates the possibility of a common therapeutic mechanism across multiple rare neuronal diseases.
Early age-related atrophy of cutaneous lymph nodes precipitates an early functional decline in skin immunity in mice with aging
Authors: Sonar Sandip Ashok , Uhrlaub Jennifer L. , Coplen Christopher P. , Sempowski Gregory D. , Dudakov Jarrod A. , van den Brink Marcel R.M. , LaFleur Bonnie J. , Jergovic Mladen , Nikolich-Žugich Janko
Published: November 2021

Secondary lymphoid organs (SLO; including the spleen and lymph nodes) are critical both for the maintenance of naïve T (TN) lymphocytes and for the initiation and coordination of immune responses. How they age, including the exact timing, extent, physiological relevance, and the nature of age-related changes, remains incompletely understood. We used time-stamping to indelibly mark cohorts of newly generated naïve T cells (a.k.a. recent thymic emigrants - RTE) in mice, and followed their presence, phenotype and retention in SLO. We found that SLO involute asynchronously. Skin-draining lymph nodes (LN) atrophied early (6-9 months) in life and deeper tissue-draining LN and the spleen late (18-20 months), as measured by the loss of both TN numbers and the fibroblastic reticular cell (FRC) network. Time-stamped RTE cohorts of all ages entered SLO and successfully completed post-thymic differentiation. However, in older mice, these cells were poorly retained, and those found in SLO exhibited an emigration phenotype (CCR7loS1P1hi). Transfers of adult RTE into recipients of different ages formally demonstrated that the defect segregates with the age of the SLO microenvironment and not with the age of T cells. Finally, upon intradermal immunization, RTE generated in mice as early as 6-7 months of age barely participated in de novo immune responses and failed to produce well-armed effector cells. These results highlight changes in structure and function of superficial secondary lymphoid organs in laboratory mice that are earlier than expected and are consistent with the long-appreciated and pronounced reduction of cutaneous immunity with aging.
The special and general mechanism of cyanobacterial harmful algal blooms
Authors: Cheng Wenduo , Hwang Somin , Guo Qisen , Qian Leyuan , Liu Weile , Yu Yang , Li Zhenghao , Wang Tianji , Tao Yi , Cao Huansheng
Published: November 2021

Cyanobacterial harmful algal blooms (CyanoHABs) arise as cyanobacteria dominate phytoplankton communities when nutrient levels increase from oligotrophic state. From a wholistic perspective, this longstanding altered phytoplankton structure results from two conditions: one sufficient condition that cyanobacteria can grow maximally with elevated nutrients; one necessary condition that co-living algae cannot grow fast or dominate at the same levels. The sufficient condition, the ‘special’ mechanism of CyanoHABs at the population level, has been established as the synergistic interaction between superior cyanobacterial ecophysiology and elevated nutrients. But it is unknown how these functions arise or whether they are under directed evolution to water eutrophication. The necessary condition, the ‘general’ mechanism of CyanoHABs at the community level, is little understood: why co-living algae cannot form blooms as cyanobacteria? Literature and bioinformatics analyses show that the superior ecophysiology undergoes no directed positive evolution to worldwide eutrophication in general or any local eutrophic waters in particular; instead, these functions are under strong purifying selection and likely acquired through early adaptive radiation in nutrient-deficient conditions, as functions enabling extant cyanobacteria to occupy other niches. The general mechanism turns out to be quite straightforward: cyanobacteria are simple life forms and thus have lower per capita nutrient demand for growth, compared to co-existing eukaryotic algae in cell size and structure, genome size, size of genome-scale metabolic networks, cell content, nutrient requirement. Lower nutrient demand is proved by existing field nutrient supplementation. Both the special and general mechanisms of CyanoHABs are tentative frameworks awaiting further theoretic improvement and empirical assessment.
Reconstruction and variability of tropical pollination networks in the Brazilian Atlantic Forest
Authors: Pereira Juliana , Battiston Federico , Ribeiro Milton Cezar , Jordán Ferenc
Published: November 2021

Loss of biodiversity comprehends not only the extinction of individual species, but also the loss of the ecological interactions among them. Survival of species, continuation of ecosystem functioning in nature, and ecosystem services to humans depend on the maintenance of well-functioning networks of species interactions (e.g. plant-pollinator networks and food webs). Analyses of ecological networks often rely on biased and incomplete survey data, especially in species-rich areas, such as the tropics.

We used a network inference method to reconstruct pollination data compiled from a large tropical rainforest habitat extent. To gain insight into the characteristics of plant-pollinator interactions across the region, we combined the reconstructed pollination network with species distribution modeling to obtain local pollination networks throughout the area. We explored how global network properties relate to natural forest cover and land cover heterogeneity.

We found that some network properties (the sum and evenness of link weights, connectance and nestedness) are positively correlated with forest cover, indicating that networks in sites with more natural habitat have greater diversity of interactions, stability and resilience. Modularity was not related to forest cover, but seemed to reflect habitat heterogeneity, due to the broad spatial scale of the study.

We believe that the methodology suggested here can facilitate the use of incomplete network data in a reliable way, and allow us to better understand and protect networks of species interactions in high biodiversity regions of the world.
Genome Assembly and Population Resequencing Reveal the Geographical Divergence of ‘Shanmei’ (Rubus corchorifolius)
Authors: Yang Yinqing , Zhang Kang , Xiao Ya , Zhang Lingkui , Huang Yile , Li Xing , Chen Shumin , Peng Yansong , Yang Shuhua , Liu Yongbo , Cheng Feng
Published: November 2021

Rubus corchorifolius(‘Shanmei’ or mountain berry, 2n =14) is widely distributed in China, and its fruit has high nutritional and medicinal values. Here, we report a high-quality chromosome-scalegenome assemblyof Shanmei, with a size of 215.69 Mb and encompassing 26,696 genes. Genome comparisons among Rosaceae species show that Shanmei and Fupenzi (Rubus chingiiHu) are most closely related, and then is blackberry (Rubus occidentalis). Furtherresequencingof 101 samples of Shanmei collected from four regions in provinces of Yunnan, Hunan, Jiangxi, and Sichuan in South China reveals that the Hunan population of Shanmei possesses the highest diversity and may represent the relatively more ancestral population. Moreover, the Yunnan population undergoes strong selection based on nucleotide diversity, linkage disequilibrium, and the historical effective population size analyses. Furthermore, genes from candidate genomic regions that show strongdivergenceare significantly enriched in flavonoid biosynthesis and plant hormone signal transduction, indicating the genetic basis of adaptation of Shanmei to the local environments. The high-quality genome sequences and the variome dataset of Shanmei provide valuable resources for breeding applications and for elucidating thegenome evolutionand ecological adaptation ofRubusspecies.
Architecture of the Human Default Mode Network: Cytoarchitecture, Wiring and Signal Flow
Authors: Paquola Casey , Garber Margaret , Fraessle Stefan , Royer Jessica , Zhou Yigu , Tavakol Shahin , Rodriguez-Cruces Raul , Cabalo Donna Gift , Valk Sofie L , Eickhoff Simon , Margulies Daniel S , Evans Alan C , Amunts Karin , Jefferies Elizabeth , Smallwood Jonathan , Bernhardt Boris
Published: November 2021

The default mode network (DMN) is implicated in many aspects of complex thought and behavior. Here, we leverage post-mortem histology and in vivo neuroimaging to characterise the anatomy of the DMN to better understand its role in information processing and cortical communication. Our results show that the DMN is cytoarchitecturally heterogenous, containing cytoarchitectural types that are variably specialised for unimodal, heteromodal, and memory-related processing. Studying diffusion-based structural connectivity in combination with cytoarchitecture, we found the DMN contains regions receptive to input from sensory cortex and a core that is relatively insulated from environmental input. Finally, analysis of signal flow with effective connectivity models showed that the DMN is unique amongst cortical networks in balancing its output across the levels of sensory hierarchies. Together, our study establishes an anatomical foundation from which mechanistic accounts of the broad role the DMN plays in human brain function and cognition can be developed.
“Comparative genomics and pangenomics of vancomycin resistant and susceptibleEnterococcus faeciumfrom Irish hospitals across 20 years”
Authors: Leigh R.J. , McKenna C. , McWade R. , Lynch B. , Walsh F.
Published: November 2021

Enterococcus faeciumhas emerged as an important nosocomial pathogen, which is increasingly difficult to treat due to the genetic acquisition of vancomycin resistance. Ireland exhibits a recalcitrant vancomycin resistant bloodstream infection rate compared to other developed countries. A set of 28 vancomycin resistant isolates was sequenced to construct a dataset alongside 61 other publicly available Irish genomes. This dataset was extensively analysed usingin-silicomethodologies and uncovered distinct evolutionary, coevolutionary, and clinically relevant population trends. These results suggest that a stable (in terms of genome size, GC%, and number of genes), yet genetically diverse population (in terms of gene content) ofEnterococcus faeciumpersist in Ireland with acquired resistance arisingviaplasmid acquisition (vanA) or to a lesser extent, chromosomal recombination (vanB). Population analysis described five clusters with one cluster partitioned into four clades which transcend isolation dates. Pangenomic and recombination analyses revealed an open (whole genome and chromosomal specific) pangenome illustrating a rampant evolutionary pattern. Comparative resistomics and virulomics uncovered distinct chromosomal and mobilomal propensity for multidrug resistance, widespread chromosomal point-mutation mediated resistance, and chromosomal harboured arsenals of virulence factors. Comparative phagomics revealed a core prophagome of three prophages throughout the dataset. Interestingly, a potential difference in biofilm formation strategies was highlighted by coevolutionary analysis, suggesting differential biofilm genotypes betweenvanAandvanBisolates. These results highlight the evolutionary history of IrishEnterococcus faeciumisolates and may provide an insight into underlying infection dynamics in a clinical setting.
Human visual gamma for color stimuli: When LGN drive is equalized, red is not special
Authors: Stauch Benjamin Johannes , Peter Alina , Ehrlich Isabelle , Nolte Zora , Fries Pascal
Published: November 2021

Strong gamma-band oscillations in primate early visual cortex can be induced by spatially homogeneous, high-contrast stimuli, such as color surfaces. Compared to other hues, particularly strong gamma oscillations have been reported for red stimuli. However, precortical color processing and the resultant strength of input to V1 has often not been fully controlled for. This leaves the possibility that stronger responses to some hues were due to differences in V1 input strength. We presented stimuli that had equal luminance and color contrast levels in a color coordinate system based on color responses of the lateral geniculate nucleus, the main input source for area V1. With these stimuli, we recorded magnetoencephalography in 30 human subjects. We found narrowband color-induced gamma oscillations in early visual cortex, which, contrary to previous reports, did not differ between red and green stimuli of equal L-M cone contrast. Notably, blue stimuli with contrast exclusively on the S-cone axis induced very weak gamma responses, as well as smaller event-related fields and poorer change detection performance. The strength of human color gamma responses could be well explained by the strength of thalamic input induced by each hue and does not show a clear red bias when this input strength is properly equalized.
A Neurostimulator System for Real, Sham, and Multi-Target Transcranial Magnetic Stimulation
Authors: Sorkhabi Majid Memarian , Denison Timothy
Published: November 2021

Abstract

Background

Transcranial magnetic stimulation (TMS) is a clinically effective therapeutic instrument used to modulate neural activity. Despite three decades of research, two challenging issues remain, the possibility of changing the 1) stimulated spot and 2) stimulation type (real or sham) without physically moving the coil.

Objective

In this study, a second-generation programmable TMS (pTMS2) device with advanced stimulus shaping is introduced that uses a 5-level cascaded H-bridge inverter and phase-shifted pulse-width modulation (PWM). The principal idea of this research is to obtain real, sham, and multi-locus stimulation with the same TMS system.

Methods

We propose a two-channel modulation-based magnetic pulse generator and a novel coil arrangement, consisting of two circular coils with a physical distance of 20 mm between the coils and a control method for modifying the effective stimulus intensity, which leads to the live steerability of the location and type of stimulation.

Results

Based on the measured system performance, the stimulation profile can be steered ± 20 mm along a line from the centroid of the coil locations by modifying the modulation index.

Conclusion

The proposed system supports electronic control of the stimulation spot without physical coil movement, resulting in tunable modulation of targets, which is a crucial step towards automated TMS machines.
Single organoid RNA-sequencing reveals high organoid-to-organoid variability
Authors: Gehling Kristin , Parekh Swati , Schneider Farina , Kirchner Marcel , Kondylis Vangelis , Nikopoulou Chrysa , Tessarz Peter
Published: November 2021

Over the last decades, organoids have been established from the majority of tissue resident stem and iPS cells. They hold great promise for our understanding of mammalian organ development, but also for the study of disease or even personalized medicine. In recent years, several reports hinted at intraculture organoid variability, but a systematic analysis of such a heterogeneity has not been performed before. Here, we used RNA-seq of individual organoids to address this question. Importantly, we find that batch-to-batch variation is very low, even when prepared by different researchers. On the other hand, there is organoid-to-organoid variability within a culture. Using differential gene expression, we did not identify specific pathways that drive this variability, pointing towards possible effects of the microenvironment within the culture condition. Taken together, our study provides a framework for organoid researchers to properly consider experimental design.
A metagenomic DNA sequencing assay that is robust against environmental DNA contamination
Authors: Mzava Omary , Cheng Alexandre Pellan , Chang Adrienne , Smalling Sami , Kounatse Liz-Audrey Djomnang , Lenz Joan , Longman Randy , Steadman Amy , Salvatore Mirella , Suthanthiran Manikkam , Lee John R. , Mason Christopher E. , Dadhania Darshana , De Vlaminck Iwijn
Published: November 2021

Metagenomic DNA sequencing is a powerful tool to characterize microbial communities but is sensitive to environmental DNA contamination, in particular when applied to samples with low microbial biomass. Here, we present contamination-free metagenomic DNA sequencing (Coffee-seq), a metagenomic sequencing assay that is robust against environmental contamination. The core idea of Coffee-seq is to tag the DNA in the sample prior to DNA isolation and library preparation with a label that can be recorded by DNA sequencing. Any contaminating DNA that is introduced in the sample after tagging can then be bioinformatically identified and removed. We applied Coffee-seq to screen for infections from microorganisms with low burden in blood and urine, to identify COVID-19 co-infection, to characterize the urinary microbiome, and to identify microbial DNA signatures of inflammatory bowel disease in blood.
Increased heterogeneity and task-related reconfiguration of functional connectivity within a lexicosemantic network in autism
Authors: Sridhar Apeksha , Keehn R. Joanne Jao , Wilkinson Molly , Gao Yangfeifei , Olson Michael , Mash Lisa E , Alemu Kalekirstos , Manley Ashley , Marinkovic Ksenija , Linke Annika , Müller Ralph-Axel
Published: November 2021

Autism spectrum disorder (ASD) is highly heterogeneous in etiology and clinical presentation. Findings on intrinsic functional connectivity (FC) or task-induced FC in ASD have been inconsistent including both over- and underconnectivity and diverse regional patterns. As FC patterns change across different cognitive demands, a novel and more comprehensive approach to network architecture in ASD is to examine the change in FC patterns between rest and task states, referred to as reconfiguration. This approach is suitable for investigating inefficient network connectivity that may underlie impaired behavioral functioning in clinical disorders. We used functional magnetic resonance imaging (fMRI) to examine FC reconfiguration during lexical processing, which is often affected in ASD, with additional focus on interindividual variability. Thirty adolescents with ASD and a matched group of 23 typically developing (TD) participants completed a lexicosemantic decision task during fMRI, using multiecho-multiband pulse sequences with advanced BOLD signal sensitivity and artifact removal. Regions of interest (ROIs) were selected based on task-related activation across both groups, and FC and reconfiguration were compared between groups. The ASD group showed increased interindividual variability and overall greater reconfiguration than the TD group. An ASD subgroup with typical performance accuracy (at the level of TD participants) showed reduced similarity and typicality of FC during the task. In this ASD subgroup, greater FC reconfiguration was associated with increased language skills. Findings suggest that intrinsic functional networks in ASD may be inefficiently organized for lexicosemantic decisions and may require greater reconfiguration during task processing, with high performance levels in some individuals being achieved through idiosyncratic mechanisms.

Highlights

FC reconfiguration is a comprehensive approach to examining network architecture

Functional networks are inefficiently organized for lexicosemantic decisions in ASD

ASD may require greater reconfiguration during task processing

Some ASD individuals achieve high performance through idiosyncratic mechanisms
Thermodynamic Constraints on Electromicrobial Protein Production
Authors: Wise Lucas , Marecos Sabrina , Randolph Katie , Nshimyumukiza Eric , Hassan Mohamed , Strouse Jacob , Salimijazi Farshid , Barstow Buz
Published: November 2021

Global consumption of protein is projected to double by the middle of the 21st century1. However, protein production is one of the most energy intensive and environmentally damaging parts of the food supply system today. Electromicrobial production technologies that combine renewable electricity and CO2-fixing microbial metabolism could dramatically increase the energy efficiency of commodity chemical production2–5. Here we present a molecular-scale model that sets an upper limit on the performance of any organism performing electromicrobial protein production. We show that engineered microbes that fix CO2 and N2 using reducing equivalents produced by H2-oxidation or extracellular electron uptake could produce amino acids with energy inputs as low as 64 MJ kg-1. This work provides a roadmap for development of engineered microbes that could significantly expand access to proteins produced with a low environmental footprint.
COVID-19 vaccination and menstrual cycle changes: A United Kingdom (UK) retrospective case-control study
Authors: Alvergne Alexandra , Kountourides Gabriella , Argentieri M. Austin , Agyen Lisa , Rogers Natalie , Knight Dawn , Sharp Gemma C , Maybin Jacqueline A , Olszewska Zuzanna
Published: November 2021

Background

There has been increasing public concern that COVID-19 vaccines cause menstrual cycle disturbances, yet there is currently limited data to evaluate the impact of vaccination on menstrual health. Our objectives were (1) to evaluate the prevalence of menstrual changes following vaccination against COVID-19, (2) to test potential risk factors for any such changes, and (3) to identify patterns of symptoms in participants’ written accounts.

Methods

We performed a secondary analysis of a retrospective online survey titled “The Covid-19 Pandemic and Women’s Reproductive Health”, conducted in March 2021 in the UK before widespread media attention regarding potential impacts of SARS-CoV-2 vaccination on menstruation. Participants were recruited via a Facebook ad campaign in the UK and eligibility criteria for survey completion were age greater than 18 years, having ever menstruated and currently living in the UK. In total, 26,710 people gave consent and completed the survey. For this analysis we selected 4,989 participants who were pre-menopausal and vaccinated. These participants were aged 28 to 43, predominantly from England (81%), of white background (95%) and not using hormonal contraception (58%).

Findings

Among pre-menopausal vaccinated individuals (n=4,989), 80% did not report any menstrual cycle changes up to 4 months after their first COVID-19 vaccine injection. Current use of combined oral contraceptives was associated with lower odds of reporting any changes by 48% (OR = 0.52, 95CI = [0.34 to 0.78],P<0.001). Odds of reporting any menstrual changes were increased by 44% for current smokers (OR = 1.44, 95CI = [1.07 to 1.94],P<0.01) and by more than 50% for individuals with a positive COVID status [Long Covid (OR = 1.61, 95CI = [1.28 to 2.02],P<0.001), acute COVID (OR = 1.54, 95CI = [1.27 to 1.86],P<0.001)]. The effects remain after adjusting for self-reported magnitude of menstrual cycle changes over the year preceding the survey. Written accounts report diverse symptoms; the most common words include “cramps”, “late”, “early”, “spotting”, “heavy” and “irregular”, with a low level of clustering among them.

Conclusions

Following vaccination for COVID-19, menstrual disturbance occurred in 20% of individuals in a UK sample. Out of 33 variables investigated, smoking and a previous history of SARS-CoV-2 infection were found to be risk factors while using oestradiol-containing contraceptives was found to be a protective factor. Diverse experiences were reported, from menstrual bleeding cessation to heavy menstrual bleeding.