bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anococcygeal Nerve and Sitting Pain
Authors: Alimehmeti Ridvan H. , Schuenke Mark D. , Dellon A. Lee 
Published: October 2021

Background
The plastic surgeon is often asked to reconstruct the sacral area related to pilonidal cysts or a tumor, or after other surgery, such as coccygectomy. When sitting pain is not due to the pudendal or posterior femoral cutaneous nerve injury, the anococcygeal nerve (ACN) must be considered. Clinically, its anatomy is not well known. Rather than consider coccygectomy when the traditional nonoperative treatment of coccydynia fails, resection of the ACN might be considered.

Methods
A review of traditional anatomy textbooks was used to establish classical thoughts about the ACN. A retrospective cohort of patients with sitting pain related to the coccyx was examined, and those operated on, by resecting the ACN, were examined for clinicopathologic correlations.

Results
When the ACN is described in anatomy textbooks, it is with varying distributions of innervated skin territory and nerve root composition. Most include an origin from sacral 5 and coccygeal 1 ventral roots. Most agree that the ACN forms on the ventral side of the sacrum/coccyx, alongside the coccygeus muscle, to emerge laterally and travel dorsally to innervate skin over the coccyx and lower sacrum. A review of 13 patients with sitting pain due to the ACN, from 2015 to 2019, demonstrated a mean age of 54.6 years. Eleven were female. The etiologies of ACN injury were falls (9), exercise (3), and complication from surgery (1). Six of the 9 patients who had surgery were able to be followed up with a mean length of 36.3 months (range, 11–63 months). Overall, 3 had an excellent result, 2 had a good result, and 1 was not improved. The one with a failed result showed improvement with coccygectomy.

Conclusions
The ACN must be included in the differential diagnosis of sitting pain. It is most often injured by a fall. The ACN can be evaluated with a diagnostic nerve block, can be identified at surgery, and can be resected, and its proximal end can be implanted into the coccygeus muscle. This surgery may prove an alternative to coccygectomy.
Impaired Neutralizing Antibody Response to COVID-19 mRNA Vaccines in Cancer Patients
Authors: Zeng Cong , Evans John P. , Reisinger Sarah , Woyach Jennifer , Liscynesky Christina , Boghdadly Zeinab El , Rubinstein Mark P. , Chakravarthy Karthik , Saif Linda , Oltz Eugene M. , Gumina Richard J. , Shields Peter G. , Li Zihai , Liu Shan-Lu 
Published: October 2021

AbstractThere is currently a critical need to determine the efficacy of SARS-CoV-2 vaccination for immunocompromised patients. In this study, we determined the neutralizing antibody response in 160 cancer patients diagnosed with chronic lymphocytic leukemia (CLL), lung cancer, breast cancer, and various non-Hodgkin’s lymphomas (NHL), after they received two doses of mRNA vaccines. Serum from 46 mRNA vaccinated health care workers (HCWs) served as healthy controls. We discovered that (1) cancer patients exhibited reduced neutralizing antibody titer (NT50) compared to HCWs; (2) CLL and NHL patients exhibited the lowest NT50levels, with 50-60% of them below the detection limit; (3) mean NT50levels in patients with CLL and NHL was ∼2.6 fold lower than those with solid tumors; and (4) cancer patients who received anti-B cell therapy exhibited significantly reduced NT50levels. Our results demonstrate an urgent need for novel immunization strategies for cancer patients against SARS-CoV-2, particularly those with hematological cancers and those on anti-B cell therapies.
CLUH controls astrin-1 expression to couple mitochondrial metabolism to cell cycle progression
Authors: Schatton Désirée , Pietro Giada Di , Szczepanowska Karolina , Veronese Matteo , Marx Marie-Charlotte , Braunöhler Kristina , Barth Esther , Müller Stefan , Giavalisco Patrick , Langer Thomas , Trifunovic Aleksandra , Rugarli Elena I. 
Published: October 2021

AbstractProliferating cells undergo metabolic changes in synchrony with cell cycle progression and cell division. Mitochondria provide fuel, metabolites, and ATP during different phases of the cell cycle, however it is not completely understood how mitochondrial function and the cell cycle are coordinated. CLUH is a post-transcriptional regulator of mRNAs encoding mitochondrial proteins involved in oxidative phosphorylation and several metabolic pathways. Here, we show a role of CLUH in regulating the expression of astrin, which is involved in metaphase to anaphase progression, centrosome integrity, and mTORC1 inhibition. We find that CLUH binds both the SPAG5 mRNA and its product astrin, and controls the synthesis and the stability of the full-length astrin-1 isoform. We show that CLUH interacts with astrin-1 specifically during interphase. Astrin-depleted cells show mTORC1 hyperactivation and enhanced anabolism. On the other hand, cells lacking CLUH show decreased astrin levels and increased mTORC1 signaling, but cannot sustain anaplerotic and anabolic pathways. In absence of CLUH, cells fail to grow during G1, and progress faster through the cell cycle, indicating dysregulated matching of growth, metabolism and cell cycling. Our data reveal a role of CLUH in coupling growth signaling pathways and mitochondrial metabolism with cell cycle progression.
Tropical-temperate dichotomy falls apart in the Asian Palmate Group of Araliaceae
Authors: Coca-de-la-Iglesia Marina , Medina Nagore G. , Wen Jun , Valcárcel Virginia 
Published: October 2021

ABSTRACTPREMISEThe use of climatic data on phylogenetic studies has greatly increased in the last decades. High-quality spatial data and accurate climatic information are essential to minimize errors in the climatic reconstructions to the past. However, despite the huge amount of already available biodiversity digital information, the process of compiling, cleaning, and comparing spatial data from different open data sources is a time-consuming task that sometimes ends up with low-quality geographical information. For this reason, researchers often resort qualitative approximations among which World bioclimatic classification systems or the experts’ criteria are the most used. Our aim is to evaluate the climatic characterization of the genera of the Asian Palmate Group (AsPG) of the ginseng family (Araliaceae), one of the classical examples of tropical-temperate plant families.METHODSWe compiled a curated worldwide spatial database of the AsPG genera. We then created five raster layers representing bioclimatic regionalizations of the World. Finally, we crossed the database with the layers to characterize the AsPG genera.RESULTSWe found large disagreement in the climatic characterization of genera among regionalizations and little support for the tropical-temperate dichotomy. Both results are attributed to the complexity of delimiting tropical, subtropical and temperate climates in the World and to the distribution of the study group in regions with transitional climatic conditions.CONCLUSIONSThe complexity in the climatic classification of this classical example tropical-temperate dichotomy, calls for a general revision in other families. In fact, we claim that to properly evaluate tropical-temperate transitions we cannot ignore the complexity of distribution ranges.
HiIDDD: A high-throughput imaging pipeline for the quantitative detection of DNA damage in primary human immune cells
Authors: Gallant Kelsey , Bektas Arsun , Kaileh Mary , Lustig Ana , Ferrucci Luigi , Pegoraro Gianluca , Misteli Tom 
Published: October 2021

AbstractDNA damage is a prominent biomarker for numerous diseases, including cancer and aging. Detection of DNA damage routinely relies on traditional microscopy or cytometric methods. However, these techniques are typically of limited throughput and are not ideally suited for large-scale longitudinal and population studies that require analysis of large sample sets. We have developed HiIDDD (High-throughput Immune cell DNA Damage Detection), a robust, semiquantitative and single-cell assay that measures DNA damage by high-throughput imaging using the two major DNA damage markers 53BP1 and γ−H2AX. We demonstrate sensitive detection of DNA damage in a wide set of freshly isolated and cryopreserved primary human immune cells, including CD4+ and CD8+ T cells, B cells and monocytes with low inter-assay variability. As proof of principle, we demonstrate parallel batch processing of several immune cell types from multiple donors. We find common patterns of DNA damage in multiple immune cell types of donors of varying ages, suggesting that immune cell properties are specific to individuals. These results establish a novel high-throughput assay for the evaluation of DNA damage in large-scale studies.
Dynamic chromosomal interactions and control of heterochromatin positioning by Ki-67
Authors: van Schaik Tom , Manzo Stefano G. , Vouzas Athanasios E. , Liu Ning Qing , Teunissen Hans , de Wit Elzo , Gilbert David M. , van Steensel Bas 
Published: October 2021

AbstractKi-67 is a chromatin-associated protein with a dynamic distribution pattern throughout the cell cycle, and is thought to be involved in chromatin organization. Lack of genomic interaction maps has hampered a detailed understanding of its roles, particularly during interphase. By pA-DamID mapping in human cell lines we found that Ki-67 associates with large genomic domains that overlap mostly with late-replicating regions. Early in interphase, when Ki-67 is present in pre-nucleolar bodies, it interacts with these domains on all chromosomes. However, later in interphase, when Ki-67 is confined to nucleoli, it shows a striking shift towards small chromosomes. Nucleolar perturbations indicate that these cell cycle dynamics correspond to nucleolar maturation during interphase, and suggest that nucleolar sequestration of Ki-67 limits its interactions with larger chromosomes. Furthermore, we demonstrate that Ki-67 does not detectably control chromatin-chromatin interactions during interphase, but it competes with the nuclear lamina for interaction with late-replicating DNA, and it controls replication timing of (peri)centromeric regions. Together, these results reveal a highly dynamic choreography of genome interactions and roles for Ki-67 in heterochromatin organization.
Human milk oligosaccharides reduce murine group B Streptococcus vaginal colonization with minimal impact on the vaginal microbiota
Authors: Mejia Marlyd E. , Ottinger Samantha , Vrbanac Alison , Babu Priyanka , Zulk Jacob , Moorshead David , Bode Lars , Nizet Victor , Patras Kathryn A. 
Published: October 2021

ABSTRACTGroup B Streptococcus (GBS) colonizes the vaginal mucosa of a significant percentage of healthy women and is a leading cause of neonatal bacterial infections. Currently, pregnant women are screened in the last month of pregnancy and GBS-positive women are given antibiotics during parturition to prevent bacterial transmission to the neonate. Recently, human milk oligosaccharides (HMOs) isolated from breastmilk were found to inhibit GBS growth and biofilm formation in vitro, and women that make certain HMOs are less likely to be vaginally colonized with GBS. Using in vitro human vaginal epithelial cells and a murine vaginal colonization model, we tested the impact of HMO treatment on GBS burdens and the composition of the endogenous microbiota by 16S rRNA amplicon sequencing. HMO treatment reduced GBS vaginal burdens in vivo with minimal alterations to the vaginal microbiota. HMOs displayed potent inhibitory activity against GBS in vitro, but HMO pretreatment did not alter adherence of GBS or the probiotic Lactobacillus rhamnosus to human vaginal epithelial cells. Additionally, disruption of a putative GBS glycosyltransferase (Δsan_0913) rendered the bacterium largely resistant to HMO inhibition in vitro and in vivo but did not compromise its adherence, colonization, or biofilm formation in the absence of HMOs. We conclude that HMOs are a promising therapeutic bioactive to limit GBS vaginal colonization with minimal impacts on the vaginal microenvironment.IMPORTANCEDuring pregnancy, GBS ascension into the uterus can cause fetal infection or preterm birth. Additionally, GBS exposure during labor creates a risk of serious disease in the vulnerable newborn and mother postpartum. Current recommended prophylaxis consists of administering broad-spectrum antibiotics to GBS-positive mothers during labor. Although antibiotics have significantly reduced GBS neonatal disease, there are several unintended consequences including altered neonatal gut bacteria and increased risk for other types of infection. Innovative preventions displaying more targeted antimicrobial activity, while leaving the maternal microbiota intact, are thus appealing. Using a mouse model, we found that human milk oligosaccharides (HMOs) reduce GBS burdens without perturbing the vaginal microbiota. We conclude that HMOs are a promising alternative to antibiotics to reduce GBS neonatal disease.
The endophilin curvature-sensitive motif requires electrostatic guidance to recycle synaptic vesicles in vivo
Authors: Zhang Lin , Wang Yu , Dong Yongming , Pant Aaradhya , Liu Yan , Masserman Laura , McLaughlin Richard N , Bai Jihong 
Published: October 2021

AbstractCurvature-sensing mechanisms assist proteins in executing particular actions on various membrane organelles. Here, we investigated the functional specificity of curvature-sensing amphipathic motifs through the study of endophilin, an endocytic protein for synaptic vesicle recycling. We generated chimeric endophilin proteins by replacing the endophilin amphipathic motif H0 with other curvature-sensing amphipathic motifs. We found that the role of amphipathic motifs cannot simply be extrapolated from the identity of their parental proteins. For example, the amphipathic motif of the nuclear pore complex protein NUP133 functionally replaced the synaptic role of endophilin H0. Interestingly, non-functional endophilin chimeras had similar defects – producing fewer synaptic vesicles but more endosomes – indicating that the curvature-sensing motifs in these chimeras have a common deficiency at reforming synaptic vesicles. Finally, we converted non-functional endophilin chimeras into functional proteins by changing the cationic property of amphipathic motifs, setting a precedent for reprogramming the functional specificity of curvature-sensing motifs in vivo.
A novel innate pathogen sensing strategy involving ubiquitination of bacterial surface proteins
Authors: Apte Shruti , Bhutda Smita , Ghosh Sourav , Sharma Kuldeep , Sahay Osheen , Rakshit Jyotirmoy , Sinha Akash Raj , Dibyachintan Soham , Roy Suvapriya , Datey Akshay , Santra Shweta , Joseph Jincy , Sasidharan Sreeja , Hammerschmidt Sven , Chakravortty Dipshikha , Santra Manas , Banerjee Anirban 
Published: October 2021

AbstractSensing of pathogens by ubiquitination is critical for maintaining cytosolic sanctity. However, universal ubiquitination targets on bacteria, especially of proteinaceous origin, remain unidentified. Here, we unveil a novel strategy, involving recognition of degron-like motifs for identification of first protein-based ubiquitination substrates on phylogenetically distinct bacteria. Such motifs can form a new class of intra-cytosolic pathogen associated molecular patterns (PAMPs) as their incorporation enables identification of non-ubiquitin targets by host Ub-ligases. We find SCFFBW7E3-ligase, supported by the regulatory kinase, GSK3β, is crucial for effective pathogen detection and clearance. This may explain the enhanced risk of infections in Chronic Lymphocytic Leukaemia patients bearing FBXW7 mutations. We conclude that exploitation of such ubiquitous pathogen sensing strategy allows conservation of cellular resources and boost anti-microbial immunity.One Sentence SummaryUbiquitination of bacterial surface proteins fosters sensing and clearance of diverse pathogens
A transcriptional constraint mechanism limits the homeostatic response to activity deprivation in mammalian neocortex
Authors: Valakh Vera , Wise Derek , Zhu Xiaoyue Aelita , Sha Mingqi , Fok Jaidyn , Van Hooser Stephen D. , Schectman Robin , Cepeda Isabel , Kirk Ryan , O’Toole Sean , Nelson Sacha B. 
Published: October 2021

AbstractHealthy neuronal networks rely on homeostatic plasticity to maintain stable firing rates despite changing synaptic drive. These mechanisms, however, can themselves be destabilizing if activated inappropriately or excessively. For example, prolonged activity deprivation can lead to rebound hyperactivity and seizures. While many forms of homeostasis have been described, whether and how the magnitude of homeostatic plasticity is constrained remains unknown. Here we uncover negative regulation of cortical network homeostasis by the PARbZIP family of transcription factors. In cortical slice cultures made from knockout mice lacking all three of these factors, the network response to prolonged activity withdrawal measured with calcium imaging is much stronger, while baseline activity is unchanged. Whole cell recordings reveal an exaggerated increase in the frequency of miniature excitatory synaptic currents reflecting enhanced upregulation of recurrent excitatory synaptic transmission. Genetic analyses reveal that two of the factors, Hlf and Tef, are critical for constraining plasticity and for preventing life-threatening seizures. These data indicate that transcriptional activation is not only required for many forms of homeostatic plasticity but is also involved in restraint of the response to activity deprivation.
Classification of daily crop phenology in PhenoCams using deep learning and hidden markov models
Authors: Taylor Shawn D , Browning Dawn M 
Published: October 2021

AbstractNear surface cameras, such as those in the PhenoCam network, are a common source of ground truth data in modelling and remote sensing studies. Despite having locations across numerous agricultural sites, few studies have used near surface cameras to track the unique phenology of croplands. Due to management activities, crops do not have a natural vegetation cycle which many phenological extraction methods are based on. For example, a field may experience abrupt changes due to harvesting and tillage throughout the year. A single camera can also record several different plants due to crop rotations, fallow fields, and cover crops. Current methods to estimate phenology metrics from image time series compress all image information into a relative greenness metric, which discards a large amount of contextual information. This can include the type of crop present, whether snow or water is present on the field, the crop phenology, or whether a field lacking green plants consists of bare soil, fully senesced plants, or plant residue. Here we developed a modelling workflow to create a daily time series of crop type and phenology, while also accounting for other factors such as obstructed images and snow covered fields. We used a mainstream deep learning image classification model, VGG16. Deep learning classification models do not have a temporal component, so to account for temporal correlation among images our workflow incorporates a hidden markov model in the post-processing. The initial image classification model had out of sample F1 scores of 0.83-0.85, which improved to 0.86-0.91 after all post-processing steps. The resulting time series show the progression of crops from emergence to harvest, and can serve as a daily, local scale dataset of field states and phenological stages for agricultural research.
In vitro analysis of the effects of acetaminophen, ibuprofen and aspirin on motility of female adult Onchocerca volvulus worms
Authors: Otabil Kenneth B. , Antwi Rhoda K. , Nyarko Prince , Babae Theophilus N. , Ankrah Blessing , Bart-Plange Emmanuel J. , Kyei Rexford , Ameyaw Joseph , Bamfo Joseph G. , Gyasi Samuel F. , Schallig Henk DFH 
Published: October 2021

AbstractIn view of the very ambitious global timelines for elimination of onchocerciasis in 2030, the search for alternative antifilarials cannot depend on drug development from scratch, and repurposed drugs offer cheaper and faster alternatives. Previous studies had demonstrated the presence and potential expression of amidase, an enzyme that can be targeted by repurposed analgesics, in Onchocerca volvulus worms. The aim of this study was to determine the effects of acetaminophen, ibuprofen and aspirin on the motility of adult O. volvulus worms. In total, thirty (30) female O. volvulus worms were exposed to acetaminophen, ibuprofen and aspirin in concentrations of either 5mg/ml, 2.5mg/ml, 1.25mg/ml or 0.63mg/ml control in duplicates. Worm motility was observed and recorded using the WormAssay software and a darkfield imaging apparatus starting on day 2 of incubation and ending on day 8. Acetaminophen, ibuprofen and aspirin inhibited O. volvulus motility by 2-fold compared to control in the first 24 hours of drug exposure. However, an extended exposure of the worms to these test drugs rather improved the motility of the worms. The study has demonstrated that a 24-hour exposure of O. volvulus worms to the analgesic drugs studied, results in significant inhibition in worm motility compared with the control group, but extended duration of exposure led to an enhancement in motility of the previously immobile worms. This finding supports the idea that aspirin and ibuprofen may have some longevity enhancing properties. Further research on the utility of these analgesics as possible anti-filarial drugs is thus warranted.
Autophagy-dependent TOR reactivation drives fungal growth in living host rice cells
Authors: Li Gang , Gong Ziwen , Dulal Nawaraj , Rocha Raquel O. , Wilson Richard A. 
Published: October 2021

AbstractEukaryotic filamentous plant pathogens with biotrophic growth stages like the devastating hemibiotrophic rice blast fungus Magnaporthe oryzae grow for extended periods in living host plant cells without eliciting defense responses. M. oryzae elaborates invasive hyphae (IH) that grow in and between living rice cells while separated from host cytoplasm by plant-derived membrane interfaces. However, although critical to the plant infection process, the molecular mechanisms and metabolic strategies underpinning this intracellular growth phase are poorly understood. Eukaryotic cell growth depends on activated target-of-rapamycin (TOR) kinase signaling, which inhibits autophagy. Here, using live-cell imaging coupled with plate growth tests and RNAseq, proteomic, quantitative phosphoproteomics and metabolic approaches, we show how cycles of autophagy in IH modulate TOR reactivation via α-ketoglutarate to sustain biotrophic growth and maintain biotrophic interfacial membrane integrity in host rice cells. Deleting the M. oryzae serine-threonine protein kinase Rim15-encoding gene attenuated biotrophic growth, disrupted interfacial membrane integrity and abolished the in planta autophagic cycling we observe here for the first time in wild type. Δrim15 was also impaired for glutaminolysis and depleted for α-ketoglutarate. α-ketoglutarate treatment of Δrim15-infected leaf sheaths remediated Δrim15 biotrophic growth. In WT, α-ketoglutarate treatment suppressed autophagy. α-ketoglutarate signaling is amino acid prototrophy- and GS-GOGAT cycle-dependent. We conclude that, following initial IH elaboration, cycles of Rim15- dependent autophagic flux liberate α-ketoglutarate – via the GS-GOGAT cycle – as an amino acid-sufficiency signal to trigger TOR reactivation and promote fungal biotrophic growth in nutrient-restricted host rice cells.