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Data-informed decision making is a critical goal for many community-based public health research initiatives. However, community partners often encounter challenges when interacting with data. The Community-Engaged Data Science (CEDS) model offers a goal-oriented, iterative guide for communities to collaborate with research data scientists through data ambassadors. This study presents a case study of CEDS applied to research on the opioid epidemic in 18 counties in Ohio as part of the HEALing Communities Study (HCS). Data ambassadors provided a pivotal role in empowering community coalitions to translate data into action using key steps of CEDS which included: data landscapes identifying available data in the community; data action plans from logic models based on community data needs and gaps of data; data collection/sharing agreements; and data systems including portals and dashboards. Throughout the CEDS process, data ambassadors emphasized sustainable data workflows, supporting continued data engagement beyond the HCS. The implementation of CEDS in Ohio underscored the importance of relationship building, timing of implementation, understanding communities' data preferences, and flexibility when working with communities. Researchers should consider implementing CEDS and integrating a data ambassador in community-based research to enhance community data engagement and drive data-informed interventions to improve public health outcomes. [ABSTRACT FROM AUTHOR]

Layer 5 extratelencephalic (ET) neurons are present across neocortical areas and send axons to multiple subcortical targets1–6. Two cardinal subtypes exist7,8: (1) Slco2a1-expressing neurons (ETdist), which predominate in the motor cortex and project distally to the pons, medulla and spinal cord; and (2) Nprs1- or Hpgd-expressing neurons (ETprox), which predominate in the visual cortex and project more proximally to the pons and thalamus. An understanding of how area-specific ETdist and ETprox emerge during development is important because they are critical for fine motor skills and are susceptible to spinal cord injury and amyotrophic lateral sclerosis9–12. Here, using cross-areal mapping of axonal projections in the mouse neocortex, we identify the subtype-specific developmental dynamics of ET neurons. Whereas subsets of ETprox emerge by pruning of ETdist axons, others emerge de novo. We outline corresponding subtype-specific developmental transcriptional programs using single-nucleus sequencing. Leveraging these findings, we use postnatal in vivo knockdown of subtype-specific transcription factors to reprogram ET neuron connectivity towards more proximal targets. Together, these results show the functional transcriptional programs driving ET neuron diversity and uncover cell subtype-specific gene regulatory networks that can be manipulated to direct target specificity in motor corticofugal pathways.Using cross-areal mapping of axonal projections in the mouse neocortex, we identify the subtype-specific developmental dynamics of extratelencephalic neurons and show the functional transcriptional programs driving extratelencephalic neuron diversity. [ABSTRACT FROM AUTHOR]

Purpose of the Review: Acute postoperative pain impacts a significant number of patients and is associated with various complications, such as a higher occurrence of chronic postsurgical pain as well as increased morbidity and mortality. Recent Findings: Opioids are often used to manage severe pain, but they come with serious adverse effects, such as sedation, respiratory depression, postoperative nausea and vomiting, and impaired bowel function. Therefore, most enhanced recovery after surgery protocols promote multimodal analgesia, which includes adjuvant analgesics, to provide optimal pain control. In this article, we aim to offer a comprehensive review of the contemporary literature on adjuvant analgesics in the management of acute pain, especially in the perioperative setting. Summary: Adjuvant analgesics have proven efficacy in treating postoperative pain and reducing need for opioids. While ketamine is an established option for opioid-dependent patients, magnesium and α2-agonists have, in addition to their analgetic effect, the potential to attenuate hemodynamic responses, which make them especially useful in painful laparoscopic procedures. Furthermore, α2-agonists and dexamethasone can extend the analgesic effect of regional anesthesia techniques. However, findings for lidocaine remain inconclusive. [ABSTRACT FROM AUTHOR]

Background: Ileal pouch anal anastomosis (IPAA) circumferential pouch advancement (CPA) involves full-thickness transanal 180–360° dissection of the distal pouch, allowing the advancement of healthy bowel to cover the internal opening of a vaginal fistula. We aimed to describe the long-term outcomes of this rare procedure. Methods: Patients with IPAA who underwent transanal pouch advancement for any indication between 2009 and 2021 were included. Demographics, operative details, and outcomes were reviewed. An early fistula was defined as occurring within 1 year of IPAA construction. Clinical success was defined as resolution of symptoms necessitating CPA, pouch retention, and no stoma at the time of follow-up. Figures represent the median (interquartile range) or frequency (%). Results: Over a 12-year period, nine patients were identified; the median age at CPA was 41 (36–44) years. Four patients developed early fistula after index IPAA, and five developed late fistulae. The median number of fistula repair procedures prior to CPA was 2 (1–2). All patients were diagnosed with ulcerative colitis at the time of IPAA and all late patients were re-diagnosed with Crohn's disease. Four (44.4%) patients had ileostomies present at the time of surgery, three (33.3%) had one constructed during surgery, and two (22.2%) never had a stoma. The median follow-up time was 11 (6–24) months. Clinical success was achieved in four of the nine (44.4%) patients at the time of the last follow-up. Conclusions: Transanal circumferential pouch advancement was an effective treatment for refractory pouch vaginal fistulas and may be offered to patients who have had previous attempts at repair. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy and safety of minimally invasive tubular removal of spinal schwannoma and neurofibroma. In this single-centre study, we retrospectively analysed 49 consecutive patients who underwent minimally invasive removal of a total of 51 benign spinal nerve sheath tumors using a non-expandable (n = 18) or expandable tubular retractor (n = 33) retractor system between June 2007 and December 2019. The extent of resection, surgical complications, neurological outcome, operative time, and estimated blood loss were recorded. Histopathology revealed 41 schwannomas and 10 neurofibromas. After a mean follow-up of 30.8 months, postoperative MRI showed gross total resection in 93.7%, and subtotal resection in 6.3% of the tumors. Three patients were lost to follow up. Of the subtotal resections, one was a schwannoma (2.4% subtotal resections in schwannomas) and two were neurofibromas (20.0% subtotal resections in neurofibromas). Intraspinal and paraspinal tumor localizations were equally accessible by minimally invasive tubular surgery. Conversion to open surgery was not required in any case. The mean operative time was 167 ± 68 min, and estimated blood loss was 138 ± 145 ml. We observed no major surgical complications. Spinal schwannoma and neurofibroma can be removed effectively and safely using a minimally invasive tubular approach, with satisfying extent of tumor resection comparable to the conventional open surgical technique and no increased risk for neurological deterioration. [ABSTRACT FROM AUTHOR]

Background: BIPCOM aims to (1) identify medical comorbidities in people with bipolar disorder (BD); (2) examine risk factors and clinical profiles of Medical Comorbidities (MC) in this clinical group, with a special focus on Metabolic Syndrome (MetS); (3) develop a Clinical Support Tool (CST) for the personalized management of BD and medical comorbidities. Methods: The BIPCOM project aims to investigate MC, specifically MetS, in individuals with BD using various approaches. Initially, prevalence rates, characteristics, genetic and non-genetic risk factors, and the natural progression of MetS among individuals with BD will be assessed by analysing Nordic registers, biobanks, and existing patient datasets from 11 European recruiting centres across 5 countries. Subsequently, a clinical study involving 400 participants from these sites will be conducted to examine the clinical profiles and incidence of specific MetS risk factors over 1 year. Baseline assessments, 1-year follow-ups, biomarker analyses, and physical activity measurements with wearable biosensors, and focus groups will be performed. Using this comprehensive data, a CST will be developed to enhance the prevention, early detection, and personalized treatment of MC in BD, by incorporating clinical, biological, sex and genetic information. This protocol will highlight the study's methodology. Discussion: BIPCOM's data collection will pave the way for tailored treatment and prevention approaches for individuals with BD. This approach has the potential to generate significant healthcare savings by preventing complications, hospitalizations, and emergency visits related to comorbidities and cardiovascular risks in BD. BIPCOM's data collection will enhance BD patient care through personalized strategies, resulting in improved quality of life and reduced costly interventions. The findings of the study will contribute to a better understanding of the relationship between medical comorbidities and BD, enabling accurate prediction and effective management of MetS and cardiovascular diseases. Trial registration: ISRCTN68010602 at https://www.isrctn.com/ISRCTN68010602. Registration date: 18/04/2023. [ABSTRACT FROM AUTHOR]

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Copyright of Österreichische Wasser- und Abfallwirtschaft is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We prove in this paper, the Ax–Schanuel conjecture for all admissible variations of mixed Hodge structures. [ABSTRACT FROM AUTHOR]

Given a polarizable ℤ-variation of Hodge structures V over a complex smooth quasi-projective base S , a classical result of Cattani, Deligne and Kaplan says that its Hodge locus (i.e. the locus where exceptional Hodge tensors appear) is a countable union of irreducible algebraic subvarieties of S , called the special subvarieties for V . Our main result in this paper is that, if the level of V is at least 3, this Hodge locus is in fact a finite union of such special subvarieties (hence is algebraic), at least if we restrict ourselves to the Hodge locus factorwise of positive period dimension (Theorem 1.5). For instance the Hodge locus of positive period dimension of the universal family of degree d smooth hypersurfaces in P C n + 1 , n ≥ 3 , d ≥ 5 and (n , d) ≠ (4 , 5) , is algebraic. On the other hand we prove that in level 1 or 2, the Hodge locus is analytically dense in S an as soon as it contains one typical special subvariety. These results follow from a complete elucidation of the distribution in S of the special subvarieties in terms of typical/atypical intersections, with the exception of the atypical special subvarieties of zero period dimension. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. CRC liver metastases (CRLM) are often resistant to conventional treatments, with high rates of recurrence. Therefore, it is crucial to identify biomarkers for CRLM patients that predict cancer progression. This study utilised matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to spatially map the CRLM tumour proteome. CRLM tissue microarrays (TMAs) of 84 patients were analysed using tryptic peptide MALDI-MSI to spatially monitor peptide abundances across CRLM tissues. Abundance of peptides was compared between tumour vs stroma, male vs female and across three groups of patients based on overall survival (0-3 years, 4-6 years, and 7+ years). Peptides were then characterised and matched using LC-MS/MS. A total of 471 potential peptides were identified by MALDI-MSI. Our results show that two unidentified m/z values (1589.876 and 1092.727) had significantly higher intensities in tumours compared to stroma. Ten m/z values were identified to have correlation with biological sex. Survival analysis identified three peptides (Histone H4, Haemoglobin subunit alpha, and Inosine-5’-monophosphate dehydrogenase 2) and two unidentified m/z values (1305.840 and 1661.060) that were significantly higher in patients with shorter survival (0-3 years relative to 4-6 years and 7+ years). This is the first study using MALDI-MSI, combined with LC-MS/MS, on a large cohort of CRLM patients to identify the spatial proteome in this malignancy. Further, we identify several protein candidates that may be suitable for drug targeting or for future prognostic biomarker development. [ABSTRACT FROM AUTHOR]

The ever-growing compendium of genetic variants associated with human pathologies demands new methods to study genotype–phenotype relationships in complex tissues in a high-throughput manner1,2. Here we introduce adeno-associated virus (AAV)-mediated direct in vivo single-cell CRISPR screening, termed AAV-Perturb-seq, a tuneable and broadly applicable method for transcriptional linkage analysis as well as high-throughput and high-resolution phenotyping of genetic perturbations in vivo. We applied AAV-Perturb-seq using gene editing and transcriptional inhibition to systematically dissect the phenotypic landscape underlying 22q11.2 deletion syndrome3,4 genes in the adult mouse brain prefrontal cortex. We identified three 22q11.2-linked genes involved in known and previously undescribed pathways orchestrating neuronal functions in vivo that explain approximately 40% of the transcriptional changes observed in a 22q11.2-deletion mouse model. Our findings suggest that the 22q11.2-deletion syndrome transcriptional phenotype found in mature neurons may in part be due to the broad dysregulation of a class of genes associated with disease susceptibility that are important for dysfunctional RNA processing and synaptic function. Our study establishes a flexible and scalable direct in vivo method to facilitate causal understanding of biological and disease mechanisms with potential applications to identify genetic interventions and therapeutic targets for treating disease.An in vivo single-cell CRISPR screening method identifies transcriptional phenotypes of 22q11.2 deletion syndrome associated with a broad dysregulation of a class of disease susceptibility genes that are important for RNA processing and synaptic function. [ABSTRACT FROM AUTHOR]

Purpose: Detection of T2 hyperintensities in suspected degenerative cervical myelopathy (DCM) is done subjectively in clinical practice. To gain objective quantification for dedicated treatment, signal intensity analysis of the spinal cord is purposeful. We investigated fully automated quantification of the T2 signal intensity (T2-SI) of the spinal cord using a high-resolution MRI segmentation. Methods: Matched-pair analysis of prospective acquired cervical 3D T2-weighted sequences of 114 symptomatic patients and 88 healthy volunteers. Cervical spinal cord was segmented automatically through a trained convolutional neuronal network with subsequent T2-SI registration slice-by-slice. Received T2-SI curves were subdivided for each cervical level from C2 to C7. Additionally, all levels were subjectively classified concerning a present T2 hyperintensity. For T2-positive levels, corresponding T2-SI curves were compared to curves of age-matched volunteers at the identical level. Results: Forty-nine patients showed subjective T2 hyperintensities at any level. The corresponding T2-SI curves showed higher signal variabilities reflected by standard deviation (18.51 vs. 7.47 a.u.; p < 0.001) and range (56.09 vs. 24.34 a.u.; p < 0.001) compared to matched controls. Percentage of the range from the mean absolute T2-SI per cervical level, introduced as "T2 myelopathy index" (T2-MI), was correspondingly significantly higher in T2-positive segments (23.99% vs. 10.85%; p < 0.001). ROC analysis indicated excellent differentiation for all three parameters (AUC 0.865–0.920). Conclusion: This fully automated T2-SI quantification of the spinal cord revealed significantly increased signal variability for DCM patients compared to healthy volunteers. This innovative procedure and the applied parameters showed sufficient diagnostic accuracy, potentially diagnosing radiological DCM more objective to optimize treatment recommendation. Trial registration: DRKS00012962 (17.01.2018) and DRKS00017351 (28.05.2019) [ABSTRACT FROM AUTHOR]

An attribute-based signature (ABS), is a cryptographic scheme where someone can sign a message using any kind of predicates verified by the attributes he owns. For such scheme, it is expected to be impossible for users to collude to sign a message if none of them is originally able to sign the message on his own. The main advantage of such a solution is that the signer can remain anonymous in the set of users fulfilling the chosen predicate. It can then be used for anonymous authentication for instance. In this paper, our main contribution is a new designated verifier attribute based signature scheme. In other words, the signer is using his attributes to authenticate a message according to a predicate, and while doing so he can pick another policy such that only users owning attributes fulfilling this policy can check the validity of the signature. It can be used to extend anonymous authentication, ensuring that the designated verifier cannot prove to anyone that a valid authentication has been performed. In addition to classical anonymity, this also increases the privacy of users as no further statistics on valid connection can be deduced. To do so, we first propose a generic construction of this primitive using standard cryptographic building blocks. An instantiation of this primitive is then described and proved through security games under the Symmetric External Diffie–Hellman (SXDH ) assumption. This main contribution is compared to state-of-the-art solutions in terms of both security and efficiency. [ABSTRACT FROM AUTHOR]

Objectives: To retrospectively evaluate all cone-beam computed tomography (CBCT) scans acquired from 2017 to 2022 in a Swiss university dental clinic with particular emphasis on radiation protection aspects. Material and methods: Radiological databases at the dental clinic of the University of Bern, Switzerland, were explored using a self-developed search algorithm. Data of all acquired CBCT from 01.01.2017 to 27.06.2022 were screened. Exposure parameters (exposure time, exposure angle, milliampere (mA), kilovoltage (kV), field of view (FOV) size), dose area product (DAP), age, and sex of the patient were recorded anonymously. The collected data were analyzed mainly descriptively. Correlations measured the statistical relationships between the variables. Results: A total of 10,348 CBCT datasets were analyzed. Patient age ranged from 5 to 96 years (mean: 49.4 years, SD: 21.6 years). The number of CBCTs in patients under 25 years was around 20% each year. In total, 10,313 (99.7%) CBCTs were acquired in small to medium FOV (FOV up to 10 cm of height), and 35 (0.3%) in large FOV (height > 10 cm). DAPs of small FOVs were 518.3 ± 233.2 mGycm2 (mean ± SD), of medium FOV 1233 ± 502.2 mGycm2, and of large FOV 2189 ± 368.7 mGycm2. DAP (ρ = 0.4048, p < 0.0001) and kV (ρ = 0.0210, p = 0.0327) correlated positively with age. Reduced scan angle correlated with young age (rpb 0.2729, p < 0.001). mA did not correlate with age (p = 0.3685). Conclusions: This study demonstrates that certain well-known radiation protection aspects as the reduction of FOV, mA, kV, and scan angle were only partly considered. Clinical relevance: Known radiation protection aspects, especially in young patients, should be fully applied in regular clinical practice. [ABSTRACT FROM AUTHOR]

Objectives: Computed tomography (CT) is employed to evaluate surgical outcome after spinal interventions. Here, we investigate the potential of multispectral photon-counting computed tomography (PC-CT) on image quality, diagnostic confidence, and radiation dose compared to an energy-integrating CT (EID-CT). Methods: In this prospective study, 32 patients underwent PC-CT of the spine. Data was reconstructed in two ways: (1) standard bone kernel with 65-keV (PC-CTstd) and (2) 130-keV monoenergetic images (PC-CT130 keV). Prior EID-CT was available for 17 patients; for the remaining 15, an age–, sex–, and body mass index–matched EID-CT cohort was identified. Image quality (5-point Likert scales on overall, sharpness, artifacts, noise, diagnostic confidence) of PC-CTstd and EID-CT was assessed by four radiologists independently. If metallic implants were present (n = 10), PC-CTstd and PC-CT130 keV images were again assessed by 5-point Likert scales by the same radiologists. Hounsfield units (HU) were measured within metallic artifact and compared between PC-CTstd and PC-CT130 keV. Finally, the radiation dose (CTDIvol) was evaluated. Results: Sharpness was rated significantly higher (p = 0.009) and noise significantly lower (p < 0.001) in PC-CTstd vs. EID-CT. In the subset of patients with metallic implants, reading scores for PC-CT130 keV revealed superior ratings vs. PC-CTstd for image quality, artifacts, noise, and diagnostic confidence (all p < 0.001) accompanied by a significant increase of HU values within the artifact (p < 0.001). Radiation dose was significantly lower for PC-CT vs. EID-CT (mean CTDIvol: 8.83 vs. 15.7 mGy; p < 0.001). Conclusions: PC-CT of the spine with high-kiloelectronvolt reconstructions provides sharper images, higher diagnostic confidence, and lower radiation dose in patients with metallic implants. Key Points: • Compared to energy-integrating CT, photon-counting CT of the spine had significantly higher sharpness and lower image noise while radiation dose was reduced by 45%. • In patients with metallic implants, virtual monochromatic photon-counting images at 130 keV were superior to standard reconstruction at 65 keV in terms of image quality, artifacts, noise, and diagnostic confidence. [ABSTRACT FROM AUTHOR]

Copyright of Die Anaesthesiologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The study of the distinct structure and function of the human central nervous system, both in healthy and diseased states, is becoming increasingly significant in the field of neuroscience. Typically, cortical and subcortical tissue is discarded during surgeries for tumors and epilepsy. Yet, there is a strong encouragement to utilize this tissue for clinical and basic research in humans. Here, we describe the technical aspects of the microdissection and immediate handling of viable human cortical access tissue for basic and clinical research, highlighting the measures needed to be taken in the operating room to ensure standardized procedures and optimal experimental results. Methods: In multiple rounds of experiments (n = 36), we developed and refined surgical principles for the removal of cortical access tissue. The specimens were immediately immersed in cold carbogenated N-methyl-D-glucamine-based artificial cerebrospinal fluid for electrophysiology and electron microscopy experiments or specialized hibernation medium for organotypic slice cultures. Results: The surgical principles of brain tissue microdissection were (1) rapid preparation (<1 min), (2) maintenance of the cortical axis, (3) minimization of mechanical trauma to sample, (4) use of pointed scalpel blade, (5) avoidance of cauterization and blunt preparation, (6) constant irrigation, and (7) retrieval of the sample without the use of forceps or suction. After a single round of introduction to these principles, multiple surgeons adopted the technique for samples with a minimal dimension of 5 mm spanning all cortical layers and subcortical white matter. Small samples (5–7 mm) were ideal for acute slice preparation and electrophysiology. No adverse events from sample resection were observed. Conclusion: The microdissection technique of human cortical access tissue is safe and easily adoptable into the routine of neurosurgical procedures. The standardized and reliable surgical extraction of human brain tissue lays the foundation for human-to-human translational research on human brain tissue. [ABSTRACT FROM AUTHOR]

Changes in the mechanical properties (i.e., stiffness) of soft tissues have been linked to musculoskeletal disorders, pain conditions, and cancer biology, leading to a rising demand for diagnostic methods. Despite the general availability of different stiffness measurement tools, it is unclear as to which are best suited for different tissue types and the related measurement depths. The study aimed to compare different stiffness measurement tools' (SMT) reliability on a multi-layered phantom tissue model (MPTM). A polyurethane MPTM simulated the four layers of the thoracolumbar region: cutis (CUT), subcutaneous connective tissue (SCT), fascia profunda (FPR), and erector spinae (ERS), with varying stiffness parameters. Evaluated stiffness measurement tools included Shore Durometer, Semi-Electronic Tissue Compliance Meter (STCM), IndentoPRO, MyotonPRO, and ultrasound imaging. Measurements were made by two independent, blinded examiners. Shore Durometer, STCM, IndentoPRO, and MyotonPRO reliably detected stiffness changes in three of the four MPTM layers, but not in the thin (1 mm thick) layer simulating FPR. With ultrasound imaging, only stiffness changes in layers thicker than 3 mm could be measured reliably. Significant correlations ranging from 0.70 to 0.98 (all p < 0.01) were found. The interrater reliability ranged from good to excellent (ICC(2,2) = 0.75–0.98). The results are encouraging for researchers and clinical practitioners as the investigated stiffness measurement tools are easy-to-use and comparatively affordable. [ABSTRACT FROM AUTHOR]

Copyright of Österreichische Wasser- und Abfallwirtschaft is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The ProQ/FinO family of RNA binding proteins mediate sRNA-directed gene regulation throughout gram-negative bacteria. Here, we investigate the structural basis for RNA recognition by ProQ/FinO proteins, through the crystal structure of the ProQ/FinO domain of the Legionella pneumophila DNA uptake regulator, RocC, bound to the transcriptional terminator of its primary partner, the sRNA RocR. The structure reveals specific recognition of the 3' nucleotide of the terminator by a conserved pocket involving a β-turn-α-helix motif, while the hairpin portion of the terminator is recognized by a conserved α-helical N-cap motif. Structure-guided mutagenesis reveals key RNA contact residues that are critical for RocC/RocR to repress the uptake of environmental DNA in L. pneumophila. Structural analysis and RNA binding studies reveal that other ProQ/FinO domains also recognize related transcriptional terminators with different specificities for the length of the 3' ssRNA tail. In this work, the authors determine the crystal structure of a ProQ/FinO RNA chaperone bound to its RNA target. This provides insight into how this family of bacterial proteins recognize transcriptional terminator structures. [ABSTRACT FROM AUTHOR]

With the ever-increasing number of synthesis-on-demand compounds for drug lead discovery, there is a great need for efficient search technologies. We present the successful application of a virtual screening method that combines two advances: (1) it avoids full library enumeration (2) products are evaluated by molecular docking, leveraging protein structural information. Crucially, these advances enable a structure-based technique that can efficiently explore libraries with billions of molecules and beyond. We apply this method to identify inhibitors of ROCK1 from almost one billion commercially available compounds. Out of 69 purchased compounds, 27 (39%) have Ki values < 10 µM. X-ray structures of two leads confirm their docked poses. This approach to docking scales roughly with the number of reagents that span a chemical space and is therefore multiple orders of magnitude faster than traditional docking. Virtual screening of huge libraries is successful in identifying drug leads. Here, the authors describe a computational strategy, Chemical Space Docking, which combines docking with a reaction-based search of compounds, thereby enabling the exploration of billions of compounds and beyond. [ABSTRACT FROM AUTHOR]

Biofuels are currently the only available bulk renewable fuel. They have, however, limited expansion potential due to high land requirements and associated risks for biodiversity, food security, and land conflicts. We therefore propose to increase output from ethanol refineries in a land-neutral methanol pathway: surplus CO2-streams from fermentation are combined with H2 from renewably powered electrolysis to synthesize methanol. We illustrate this pathway with the Brazilian sugarcane ethanol industry using a spatio-temporal model. The fuel output of existing ethanol generation facilities can be increased by 43%–49% or ~100 TWh without using additional land. This amount is sufficient to cover projected growth in Brazilian biofuel demand in 2030. We identify a trade-off between renewable energy generation technologies: wind power requires the least amount of land whereas a mix of wind and solar costs the least. In the cheapest scenario, green methanol is competitive to fossil methanol at an average carbon price of 95€ tCO2−1. Fuel output of Brazilian sugarcane ethanol facilities may be increased by over 40% without using additional land if production is combined with synthetic fuel processes. This amounts to 100TWh of fuel, sparing 27,000 km2 of land. [ABSTRACT FROM AUTHOR]

Storage of platelet concentrates (PC) at cold temperature (CT) is discussed as an alternative to the current standard of storage at room temperature (RT). Recently, we could show that cold-induced attenuation of inhibitory signaling is an important mechanism promoting platelet reactivity. For developing strategies in blood banking, it is required to elucidate the time-dependent onset of facilitated platelet activation. Thus, freshly prepared platelet-rich-plasma (PRP) was stored for 1 and 2 h at CT (2–6 °C) or at RT (20–24 °C), followed by subsequent comparative analysis. Compared to RT, basal and induced vasodilator-stimulated phosphoprotein (VASP) phosphorylation levels were decreased under CT within 1 h by approximately 20%, determined by Western blot analysis and flow cytometry. Concomitantly, ADP- and collagen-induced threshold aggregation values were enhanced by up to 30–40%. Furthermore, platelet-covered areas on collagen-coated slides and aggregate formation under flow conditions were increased after storage at CT, in addition to induced activation markers. In conclusion, a time period of 1–2 h for refrigeration is sufficient to induce an attenuation of inhibitory signaling, accompanied with an enhancement of platelet responsiveness. Short-term refrigeration may be considered as a rational approach to obtain PC with higher functional reactivity for the treatment of hemorrhage. [ABSTRACT FROM AUTHOR]

The production of biopharmaceuticals relies on robust cell systems that can produce recombinant proteins at high levels and grow and survive in the stressful bioprocess environment. Chinese hamster ovary cells (CHO) as the main production hosts offer a variety of advantages including robust growth and survival in a bioprocess environment. Cell surface proteins are of special interest for the understanding of how CHO cells react to their environment while maintaining growth and survival phenotypes, since they enable cellular reactions to external stimuli and potentially initiate signaling pathways. To provide deeper insight into functions of this special cell surface sub-proteome, pathway enrichment analysis of the determined CHO surfaceome was conducted. Enrichment of growth/ survival-pathways such as the phosphoinositide-3-kinase (PI3K)–protein kinase B (AKT), mitogen-activated protein kinase (MAPK), Janus kinase/signal transducers and activators of transcription (JAK-STAT), and RAP1 pathways were observed, offering novel insights into how cell surface receptors and ligand-mediated signaling enable the cells to grow and survive in a bioprocess environment. When supplementing surfaceome data with RNA expression data, several growth/survival receptors were shown to be co-expressed with their respective ligands and thus suggesting self-induction mechanisms, while other receptors or ligands were not detectable. As data about the presence of surface receptors and their associated expressed ligands may serve as base for future studies, further pathway characterization will enable the implementation of optimization strategies to further enhance cellular growth and survival behavior. Key points: • PI3K/AKT, MAPK, JAK-STAT, and RAP1 pathway receptors are enriched on the CHO cell surface and downstream pathways present on mRNA level. • Detected pathways indicate strong CHO survival and growth phenotypes. • Potential self-induction of surface receptors and respective ligands. [ABSTRACT FROM AUTHOR]

Forests are key components of European multifunctional landscapes and supply numerous forest ecosystem services (FES) fundamental to human well-being. The sustainable provision of FES has the potential to provide responses to major societal challenges, such as climate change, biodiversity loss, or rural development. To identify suitable strategies for the future sustenance of FES, we performed a solution scanning exercise with a group of transdisciplinary forest and FES experts from different European regions. We identified and prioritized fifteen major challenges hindering the balanced provision of multiple FES and identified a series of potential solutions to tackle each of them. The most prominent challenges referred to the increased frequency and impacts of extreme weather events and the normative mindset regarding forest management. The respective solutions pointed to the promotion of forest resilience via climate-smart forestry and mainstreaming FES-oriented management through a threefold strategy focusing on education, awareness raising, and networking. In a subsequent survey, most solutions were assessed as highly effective, transferable, monitorable, and with potential for being economically efficient. The implementation of the solutions could have synergistic effects when applying the notion of leverage points. Seven emerging pathways towards the sustainable supply of FES have been identified. These pathways build on each other and are organized based on their potential for transformation: (1) shifting forest management paradigms towards pluralistic ecosystem valuation; (2) using integrated landscape approaches; (3) increasing forest resilience; (4) coordinating actions between forest-related actors; (5) increasing participation in forest planning and management; (6) continuous, open, and transparent knowledge integration; and (7) using incentive-based instruments to support regulating and cultural FES. These pathways can contribute to the implementation of the new EU Forestry Strategy to support the balanced supply of multiple FES. [ABSTRACT FROM AUTHOR]

Purpose: This study analyzed the prevalence and factors influencing the history of chronic anastomotic leakage following low anterior resection for rectal cancer. Furthermore, the treatment of a persisting presacral sinus and the impact of stoma reversal on outcome were evaluated. Methods: The institutional database was scanned for all patients with anastomotic leakage, who were primarily treated for low rectal cancer between January 1995 and December 2019. Patients with rectovaginal and rectovesical fistula or an inadequate follow-up were excluded (n = 5). After applying the exclusion criteria, 71 patients remained for analysis. Results: A total of 39 patients out of 71 patients with anastomotic leakage (54.9%) developed a persisting presacral sinus. Neoadjuvant radiochemotherapy or chemotherapy showed a significant impact on the formation of a chronic anastomotic leakage (radiochemotherapy: p = 0.034; chemotherapy: p = 0.050), while initial surgical treatment showed no difference for anastomotic healing (p = 0.502), but a significantly better overall survival (p = 0.042). Multiple therapies and surgical revision had a negative impact on patients' rate of natural bowel continuity (p = 0.006/ < 0.001). In addition, the stoma reversal cohort showed improved overall 10-year survival (p = 0.004) and functional results (bowel continuity: p = 0.026; pain: p = 0.031). Conclusion: Primary surgical therapy for chronic anastomotic leakage should consist of surgical treatment. Furthermore, the reversal of a protective stoma should be considered a viable option in treating chronic presacral sinus to improve pain symptoms and bowel continuity. [ABSTRACT FROM AUTHOR]

Introduction: Per-oral pyloromyotomy (POP or G-POEM) provides significant short-term improvements in symptoms and objective emptying for patients with medically refractory gastroparesis, but it is unclear if patients with gastroparesis and co-existing dysmotility (small bowel or colonic delay) also benefit. In this study, we used wireless motility capsule (WMC) data to measure outcomes in patients with isolated gastroparesis (GP) and gastroparesis with co-existing dysmotility (GP + Dys) who underwent POP. Methods: We retrospectively analyzed patients who had POP and completed WMC data during their evaluation of intestinal dysmotility. WMC data were reviewed to identify patients who demonstrated isolated GP or GP + Dys. Each patient's pre-op and post-op Gastroparesis Cardinal Symptom Index (GCSI) and 4-h solid-phase scintigraphy gastric emptying studies (GES) scores were compared to evaluate improvement. Results: Of the entire cohort (n = 73), 89% were female with a mean age of 47.0 ± 15.0 years old. Gastroparesis etiologies were divided among idiopathic (54.8%), diabetic (26%), postsurgical (8.2%), autoimmune (5.5%), and multifactorial (5.5%). Forty-one patients (56%) had GP and 32 patients (44%) had GP + Dys. GCSI improved after POP whether the patient had isolated GP (− 12.31, p < 0.001) or GP + Dys (− 9.58, p < 0.001); however, there was no significant difference in total GCSI improvement between the two groups. A subset of patients had postoperative GES available (n = 47). In the isolated GP and GP + Dys cohorts, 15/28 (54%) and 12/19 (63%) patients had normal post-op 4-h GES, respectively, but no statistical difference between the two groups. Conclusion: Patients with medically refractory gastroparesis with and without concomitant gastrointestinal dysmotility show short-term subjective and objective improvement after POP. Concomitant small bowel or colonic dysmotility should not deter physicians from offering POP in carefully selected patients with gastroparesis. [ABSTRACT FROM AUTHOR]

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Neocortical excitatory neurons belong to diverse cell types, which can be distinguished by their dates of birth, laminar location, connectivity, and molecular identities. During embryogenesis, apical progenitors (APs) located in the ventricular zone first give birth to deep-layer neurons, and next to superficial-layer neurons. While the overall sequential construction of neocortical layers is well-established, whether APs produce multiple neuron types at single time points of corticogenesis is unknown. To address this question, here we used FlashTag to fate-map simultaneously-born (i.e. isochronic) cohorts of AP daughter neurons at successive stages of corticogenesis. We reveal that early in corticogenesis, isochronic neurons differentiate into heterogeneous laminar, hodological and molecular cell types. Later on, instead, simultaneously-born neurons have more homogeneous fates. Using single-cell gene expression analyses, we identify an early postmitotic surge in the molecular heterogeneity of nascent neurons during which some early-born neurons initiate and partially execute late-born neuron transcriptional programs. Together, these findings suggest that as corticogenesis unfolds, mechanisms allowing increased homogeneity in neuronal output are progressively implemented, resulting in progressively more predictable neuronal identities. [ABSTRACT FROM AUTHOR]

Clinical production of 89Zr-radiolabeled antibodies (89Zr-mAbs) for positron emission tomography imaging relies on the pre-conjugation of desferrioxamine B (DFO) to the purified protein, followed by isolation and characterization of the functionalized intermediate, and then manual radiosynthesis. Although highly successful, this route exposes radiochemists to a potentially large radiation dose and entails several technological and economic hurdles that limit access of 89Zr-mAbs to just a specialist few Nuclear Medicine facilities worldwide. Here, we introduce a fully automated synthesis box that can produce individual doses of 89Zr-mAbs formulated in sterile solution in < 25 min starting from [89Zr(C2O4)4]4– (89Zr-oxalate), our good laboratory practice-compliant photoactivatable desferrioxamine-based chelate (DFO-PEG3-ArN3), and clinical-grade antibodies without the need for pre-purification of protein. The automated steps include neutralization of the 89Zr-oxalate stock, chelate radiolabeling, and light-induced protein conjugation, followed by 89Zr-mAb purification, formulation, and sterile filtration. As proof-of-principle, 89ZrDFO-PEG3-azepin-trastuzumab was synthesized directly from Herceptin in < 25 min with an overall decay-corrected radiochemical yield of 20.1 ± 2.4% (n = 3), a radiochemical purity > 99%, and chemical purity > 99%. The synthesis unit can also produce 89Zr-mAbs via the conventional radiolabeling routes from pre-functionalized DFO-mAbs that are currently used in the clinic. This automated method will improve access to state-of-the-art 89Zr-mAbs at the many Nuclear Medicine and research institutions that require automated devices for radiotracer production. [ABSTRACT FROM AUTHOR]

Background: Endoscopic per-oral pyloromyotomy (POP) has emerged as a safe and effective first line option in medically refractory gastroparesis. Determining the appropriate extent of the pyloromyotomy continues to present a challenge as there are no standardized tools for measuring changes in pyloric distensibility during the procedure. The objective of this study was to evaluate the utility of using impedance planimetry with endoscopic functional luminal imaging probe (FLIP) to measure changes in pyloric distensibility after POP, and to compare these changes with improvement in symptoms and objective gastric emptying. Methods: Patients with medically refractory gastroparesis underwent POP with FLIP measurements of the pylorus (EndoFLIP®, Medtronic, Fridley MN). FLIP measurements, as well as changes in symptoms measured by the validated gastroparesis cardinal symptom index (GCSI) and scintigraphic gastric emptying studies (GES), were evaluated before and after POP. Results: A total of 14 patients underwent measurement with FLIP during POP, 12 of whom had pre- and post-POP measurements. Mean pyloric diameter increased by 1.4 mm, from 13.9 mm to 15.3 mm (p = 0.0012). Mean distensibility index increased from 6.2 mm2/mmHg to 9.1 mm2/mmHg (p = 0.0074). Successful division of the pylorus was achieved in 100% of patients with a mean operative time of 36 min and no perioperative complications. The mean length of stay was 0.7 days (0–3 days). Post-POP mean GCSI score improved from 2.97 to 2.28 at a mean follow-up time of 27 days (p < 0.001). Objective improvement in gastric emptying was observed in 80% of patients with scintigraphic GES, with mean four-hour retention decreasing from 46.3% to 32.4% (p < 0.007). Conclusions: FLIP is a safe and feasible tool to provide objective measurements during POP. Larger cohorts with longer follow-up are required to determine if measured improvements in pyloric diameter and distensibility are predictive of sustained improvements in GCSI and GES. [ABSTRACT FROM AUTHOR]

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The end-Cretaceous Chicxulub impact triggered Earth's last mass-extinction, extinguishing ~ 75% of species diversity and facilitating a global ecological shift to mammal-dominated biomes. Temporal details of the impact event on a fine scale (hour-to-day), important to understanding the early trajectory of mass-extinction, have largely eluded previous studies. This study employs histological and histo-isotopic analyses of fossil fish that were coeval with a unique impact-triggered mass-death assemblage from the Cretaceous-Paleogene (KPg) boundary in North Dakota (USA). Patterns of growth history, including periodicity of ẟ18O and ẟ13C and growth band morphology, plus corroborating data from fish ontogeny and seasonal insect behavior, reveal that the impact occurred during boreal Spring/Summer, shortly after the spawning season for fish and most continental taxa. The severity and taxonomic symmetry of response to global natural hazards are influenced by the season during which they occur, suggesting that post-impact perturbations could have exerted a selective force that was exacerbated by seasonal timing. Data from this study can also provide vital hindsight into patterns of extant biotic response to global-scale hazards that are relevant to both current and future biomes. [ABSTRACT FROM AUTHOR]

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Interconnectivity between neocortical areas is critical for sensory integration and sensorimotor transformations1–6. These functions are mediated by heterogeneous inter-areal cortical projection neurons (ICPN), which send axon branches across cortical areas as well as to subcortical targets7–9. Although ICPN are anatomically diverse10–14, they are molecularly homogeneous15, and how the diversity of their anatomical and functional features emerge during development remains largely unknown. Here we address this question by linking the connectome and transcriptome in developing single ICPN of the mouse neocortex using a combination of multiplexed analysis of projections by sequencing16,17 (MAPseq, to identify single-neuron axonal projections) and single-cell RNA sequencing (to identify corresponding gene expression). Focusing on neurons of the primary somatosensory cortex (S1), we reveal a protracted unfolding of the molecular and functional differentiation of motor cortex-projecting ( M ⃗ ) ICPN compared with secondary somatosensory cortex-projecting ( S 2 ⃗ ) ICPN. We identify SOX11 as a temporally differentially expressed transcription factor in M ⃗ versus S 2 ⃗ ICPN. Postnatal manipulation of SOX11 expression in S1 impaired sensorimotor connectivity and disrupted selective exploratory behaviours in mice. Together, our results reveal that within a single cortical area, different subtypes of ICPN have distinct postnatal paces of molecular differentiation, which are subsequently reflected in distinct circuit connectivities and functions. Dynamic differences in the expression levels of a largely generic set of genes, rather than fundamental differences in the identity of developmental genetic programs, may thus account for the emergence of intra-type diversity in cortical neurons.Combined analysis of the connectome and transcriptome in the mouse cortex indicates that dynamic differences in expression levels of largely generic sets of genes regulate differential targeting within neuronal subtypes. [ABSTRACT FROM AUTHOR]

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Given V a polarizable variation of Z -Hodge structures on a smooth connected complex quasi-projective variety S, the Hodge locus for V ⊗ is the set of closed points s of S where the fiber V s has more Hodge tensors than the very general one. A classical result of Cattani, Deligne and Kaplan states that the Hodge locus for V ⊗ is a countable union of closed irreducible algebraic subvarieties of S, called the special subvarieties of S for V . Under the assumption that the adjoint group of the generic Mumford–Tate group of V is simple we prove that the union of the special subvarieties for V whose image under the period map is not a point is either a closed algebraic subvariety of S or is Zariski-dense in S. This implies for instance the following typical intersection statement: given a Hodge-generic closed irreducible algebraic subvariety S of the moduli space A g of principally polarized Abelian varieties of dimension g, the union of the positive dimensional irreducible components of the intersection of S with the strict special subvarieties of A g is either a closed algebraic subvariety of S or is Zariski-dense in S. [ABSTRACT FROM AUTHOR]

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Background: In peroral endoscopic myotomy for Zenker's diverticulum (Z-POEM), the cricopharyngeus muscle is divided within a submucosal tunnel started in the hypopharynx. We aimed to evaluate the safety and preliminary outcomes in patients who underwent a modified version of the Z-POEM where the tunnel is made directly overlying the cricopharyngeus, the mucosal incision and muscular interruption (MIMI) approach, and to compare these with patients who underwent a non-tunneled flexible endoscopic approach. Methods: All patients with ZD who were treated by flexible endoscopy at our institution between January 2015 and February 2020 were identified by a retrospective chart review. Dysphagia symptoms were assessed using a validated scoring system. Results: Nineteen patients with ZD underwent MIMI (mean age 76.1 years, 68.1% male) and seven patients underwent non-tunneled flexible endoscopic approach (mean age 64.4 years, 85.7% male) during the study period. Mean ZD size was 2.8 cm in the MIMI group and 1.9 cm in the non-tunneled group (p = 0.03). Clinical success was achieved in 17/19(89.5%) MIMI patients and 7/7(100%) of non-tunneled flexible endoscopic patients (p = 0.101). Dysphagia scores improved in both groups, although this difference was only significant in the MIMI group (p ≤ 0.001). Recurrence occurred in 2/17(11.7%) MIMI patients and 3/7(42.9%) non-tunneled flexible endoscopic patients (p = 0.096). There were 4 complications, including one pharyngeal perforation requiring open surgical repair in a patient with a small ZD with an associated cricopharyngeal bar in the MIMI group. Median length of follow-up was 290 [142; 465] days in the MIMI group and 1056 [258; 1206] days in the non-tunneled group (p = 0.094). Conclusions: MIMI is a technically feasible and effective treatment for ZD. Care should be taken in patients with a cricopharyngeal bar and small ZD, as this may increase the risk of perforation. Larger studies with long-term follow-up are needed to determine if MIMI reduces the risk of symptom recurrence when compared to non-tunneled flexible endoscopic approaches. [ABSTRACT FROM AUTHOR]

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It is well established that cell surface glycans play a vital role in biological processes and their altered form can lead to carcinogenesis. Mass spectrometry–based techniques have become prominent for analysing N-linked glycans, for example using matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). Additionally, MALDI MS can be used to spatially map N-linked glycans directly from cancer tissue using a technique termed MALDI MS imaging (MALDI MSI). This powerful technique combines mass spectrometry and histology to visualise the spatial distribution of N-linked glycans on a single tissue section. Here, we performed N-glycan MALDI MSI on six endometrial cancer (EC) formalin-fixed paraffin-embedded (FFPE) tissue sections and tissue microarrays (TMA) consisting of eight EC patients with lymph node metastasis (LNM) and twenty without LNM. By doing so, several putative N-linked glycan compositions were detected that could significantly distinguish normal from cancerous endometrium. Furthermore, a complex core-fucosylated N-linked glycan was detected that could discriminate a primary tumour with and without LNM. Structural identification of these putative N-linked glycans was performed using porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS). Overall, we observed higher abundance of oligomannose glycans in tumour compared to normal regions with AUC ranging from 0.85–0.99, and lower abundance of complex N-linked glycans with AUC ranges from 0.03–0.28. A comparison of N-linked glycans between primary tumours with and without LNM indicated a reduced abundance of a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2, in primary tumour with associated lymph node metastasis. In summary, N-linked glycan MALDI MSI can be used to differentiate cancerous endometrium from normal, and endometrial cancer with LNM from endometrial cancer without. [ABSTRACT FROM AUTHOR]

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle metabolism characterized by generalized muscle rigidity, increased body temperature, rhabdomyolysis, hyperkalemia and severe metabolic acidosis. The underlying mechanism of MH involves excessive Ca2+ release from myotubes via the ryanodine receptor type 1 (RYR1) and the voltage-dependent L-type calcium channel (CACNA1S). As more than 300 variants of unknown significance have been detected to date, we examined whether freely available pathogenicity prediction tools are able to detect relevant MH causing variants. In this diagnostic accuracy study, blood samples from 235 individuals with a history of a clinical malignant hyperthermia or their close relatives were genetically screened for RYR1 variants of all 106 RYR1 exons and additionally for known variants of CACNA1S. In vitro contracture tests were conducted on muscle biopsies obtained from all individuals, independently of whether a pathogenic variant, a variant of unknown significance or no variant was detected. Comparisons were made to three established bioinformatic pathogenicity detection tools to identify the clinical impact of the variants of unknown significance. All detected genetic variants were tested for pathogenicity by three in silico approaches and compared to the in vitro contracture test. Sensitivity and specificity of exon screening of all individuals listed in our MH database was analyzed. Exon screening identified 97 (41%) of the 235 individuals as carriers of pathogenic variants. Variants of unknown significance were detected in 21 individuals. Variants of unknown significance were subdivided into 19 malignant-hyperthermia-susceptible individuals and 2 non-malignant-hyperthermia-susceptible individuals. All pathogenic variants as well as the malignant-hyperthermia-suspectible variants were correctly identified by the bioinformatic prediction tools. Sensitivity of in silico approaches ranged between 0.71 and 0.98 (Polyphen 0.94 [CI 95% 0.75; 0.99]; Sift 0.98 [CI 95% 0.81; 0.99]; MutationTaster 0.92 [CI 95% 0.75; 0.99]). Specificity differed depending on the used tool (Polphen 0.98 [CI 95% 0.32; 0.99]; Sift 0.98 [CI 95% 0.32; 0.99]; MutationTaster 0.00 [CI 95% 0.00; 0.60]). All pathogenic variants and variants of unknown significance were scored as probably damaging in individuals, demonstrating a high sensitivity. Specificity was very low in one of the three tested programs. However, due to potential genotype–phenotype discordance, bioinformatic prediction tools are currently of limited value in diagnosing pathogenicity of MH-susceptible variants. [ABSTRACT FROM AUTHOR]

Purpose: The violation of the cranial adjacent facet is a frequent complication in lumbar instrumentations and can induce local pain and adjacent segment disease. Minimally invasive screw implantation is often stated as risk factor in comparison with open approaches. Percutaneous pedicle screw placement (PPSP) can be performed using single X-ray images (fluoroscopy) or intraoperative 3D navigation. The study compares top-level screws in percutaneous lumbar instrumentations regarding facet violations and screw pedicle position using navigation or fluoroscopy.Methods: Patients after lumbar PPSP were retrospectively separated according to the intraoperative technique: navigation (NAV) or fluoroscopy (FLUORO). Two blinded investigators graded the top-level screws regarding facet violations and pedicle breach in postoperative CT scans. Subsequent matched cohort analysis was performed for comparable groups.Results: Evaluating 768 screws, we assessed 70 (9.1%) facet violations. Overall, 186 (24.2%) screws were implanted using navigation. There was no significant difference in the rate of facet violations between both imaging groups (NAV 19/186, 10.2%, FLUORO 51/582, 8.8%, p = 0.55). Totally, 728 (94.8%) of all screws showed a correct pedicle position. Most of the 40 unfavorable pedicle positions were placed by fluoroscopy (NAV 4/186, 2.2%, FLUORO 36/582, 6.6%, p = 0.03). The matched cohorts verified these results (facet violations: NAV 19/186, 10.2%, FLUORO 18/186, 9.7%, p = 0.55; pedicle penetrations: NAV 4/186, 2.2%, FLUORO 12/186, 6.9%, p = 0.04).Conclusions: Both intraoperative imaging techniques allow lumbar PPSP with low rates of cranial facet violations if the surgeon intends to preserve facet integrity. Navigation was superior concerning accurate pedicle screw position, but could not significantly prevent facet violations. [ABSTRACT FROM AUTHOR]

Floodplains are often conceptualized as homogeneous sediment bodies which connect streams with their respective catchment and buffer agricultural inputs. This has led to a general bias within the hydrological community towards research on sites where the floodplain is a clear conduit for groundwater flow. In humid temperate regions of central Europe, floodplains have experienced rapid environmental changes since the last glaciation, yielding significant bedrock weathering and predominantly fine-grained, highly stratified hillslope and floodplain sediments. Such heterogeneous sedimentary architecture leads to conceptual ambiguities in the interpretation of the hydrogeological functioning of floodplains, thus raising the question: Do floodplains act as barriers or conduits to groundwater flow? This study analyzes the Ammer floodplain close to Tübingen in south-western Germany as a representative mid-section floodplain in a temperate climate where the regional bedrock-geology is dominated by mudstones. Geological, geophysical, and geochemical characterization and monitoring techniques were combined to shed light on the internal geological structure as a key control modulating the floodplain hydrology. Two partially separate groundwater systems were identified: a gravel body at the bottom of the Quaternary sediments and a Holocene confined tufaceous aquifer, separated by low-permeability clays. Despite flow being predominantly along-valley, sulfate concentrations in the floodplain aquifers showed evidence of a strong connection to the gypsum-bearing hillslope, particularly where tributary valley sediments are present (e.g., alluvial fans). Results from a floodplain water balance suggest the hillslope- and floodplain-aquifer material act as a barrier to hillslope groundwater recharge, where a large fraction may be bypassing the local floodplain groundwater system. [ABSTRACT FROM AUTHOR]

Introduction: Ramadan is characterized by a month of fasting between dawn and sunset. Cleveland Clinic Abu Dhabi is located in the United Arab Emirates, where the majority of our patients observe Ramadan. In many practices, bariatric surgery has been delayed until after Ramadan in order to avoid postoperative complications. However, there are no studies that evaluate this theory. Objectives: Our study aimed to evaluate perioperative outcomes between bariatric surgeries performed before/during Ramadan and at times distant to Ramadan. Methods: All patients who underwent primary bariatric surgery at Cleveland Clinic Abu Dhabi between September 2015 and July 2019 were retrospectively reviewed. The Pre-Ramadan (PR) cohort included patients that underwent surgery during the month of Ramadan and up to 3 months before Ramadan. The Non-Ramadan (NR) cohort included patients from the remainder 8 months. Results: Our study included 542 patients: 185 patients in the PR cohort and 357 patients in the NR cohort. Baseline characteristics were similar. There were no statistically significant differences in perioperative outcomes, including emergency department (ED) visits (23.2% PR vs. 24.4% NR, p =.77), readmission rates (2.2% PR vs. 4.5% NR, p =.17), reoperation (1.1% PR vs. 3.6% NR, p =.09), and complications within 30 days (3.8% PR vs. 7.0% NR, p =.13). Conclusions: There is no difference among patients who undergo surgery before/during Ramadan and at times distant to Ramadan. Based on this data, there does not appear to be an increased risk of performing bariatric surgery prior to or during Ramadan in a comprehensive, multi-disciplinary program. [ABSTRACT FROM AUTHOR]