Early Pennsylvanian sediment routing to the Ouachita Basin (southeastern United States) and barriers to transcontinental sediment transport sourced from the Appalachian orogen based on detrital zircon U-Pb and Hf analysis

Carboniferous sediment dispersal from the Appalachian orogenic system (eastern United States) has become a topic of widespread interest. However, the actual pathways for continental-scale, east-to-west sediment transfer have not been documented. This study presents detrital zircon (DZ) U-Pb ages and Hf isotopic values from the Lower Pennsylvanian (Morrowan) Jackfork Group and Johns Valley Shale of the synorogenic Ouachita deepwater basin of Arkansas to document provenance and delineate the likely sediment-routing systems within the broader context of sediment dispersal across Laurentia. Twelve (12) DZ U-Pb age distributions are interpreted to indicate that sediments were derived from the Appalachians to the east and northeast, as well as the midcontinent region to the north. All samples display prominent ca. 500– 400 Ma, 1250–950 Ma, 1550–1300 Ma, and 1800–1600 Ma grains, consistent with ultimate derivation from the Appalachian, Grenville, Midcontinent, and Yavapai-Mazatzal provinces. DZ Hf values obtained from the Ouachita Basin are similar to published Hf values from Pennsylvanian samples in the Appalachian and Illinois Basins. Age distributions are generally consistent for seven samples collected from the Jackfork Group and Johns Valley Shale in the southern Ouachita Mountains through ~2400 m of stratigraphic section and are interpreted to indicate little change in provenance during the Morrowan in this part of the system. However, samples from the most northern and most source-proximal site in Little Rock, Arkansas, exhibit modest percentages of Appalachian ages and elevated contributions of Yavapai-Mazatzal ages when compared with samples collected farther to the south and west. We interpret differences between DZ signatures to indicate distinct sediment-routing pathways to the Ouachita Basin. We infer the strong Appalachian and Grenville signals to represent an axial system flowing through the Appalachian foredeep, whereas the more diverse signals represent a confluence of rivers from the northeast through the backbulge of southern Illinois and western Kentucky and from the north across the Arkoma shelf. Collectively, the Ouachita Basin represents a terminal sink for sediments derived from much of the eastern and central United States.

Mechanical Comparison of a Novel Hybrid and Commercial Dorsal Double Plating for Distal Radius Fracture: In Vitro Fatigue Four-Point Bending and Biomechanical Testing

This study compares the absolute and relative stabilities of a novel hybrid dorsal double plating (HDDP) to the often-used dorsal double plating (DDP) under distal radius fracture. The “Y” shape profile with 1.6 mm HDDP thickness was obtained by combining weighted topology optimization and finite element (FE) analysis and fabricated using Ti6Al4V alloy to perform the experimental tests. Static and fatigue four-point bending testing for HDDP and straight L-plate DDP was carried out to obtain the corresponding proof load, strength, and stiffness and the endurance limit (passed at 1 × 106 load cycles) based on the ASTM F382 testing protocol. Biomechanical fatigue tests were performed for HDDP and commercial DDP systems fixed on the composite Sawbone under physiological loads with axial loading, bending, and torsion to understand the relative stability in a standardized AO OTA 2R3A3.1 fracture model. The static four-point bending results showed that the corresponding average proof load values for HDDP and DDPs were 109.22 N and 47.36 N, that the bending strengths were 1911.29 N/mm and 1183.93 N/mm, and that the bending stiffnesses were 42.85 N/mm and 4.85 N/mm, respectively. The proof load, bending strength and bending stiffness of the HDDPs were all significantly higher than those of DDPs. The HDDP failure patterns were found around the fourth locking screw hole from the proximal site, while slight plate bending deformations without breaks were found for DDP. The endurance limit was 76.50 N (equal to torque 1338.75 N/mm) for HDDP and 37.89 N (equal to torque 947.20 N/mm) for DDP. The biomechanical fatigue test indicated that displacements under axial load, bending, and torsion showed no significant differences between the HDDP and DDP groups. This study concluded that the mechanical strength and endurance limit of the HDDP was superior to a commercial DDP straight plate in the four-point bending test. The stabilities on the artificial radius fractured system were equivalent for novel HDDP and commercial DDP under physiological loads in biomechanical fatigue tests.

Delayed primary fascia closure of Björck grade 4 open abdomen with enteroatmospheric fistulas after repeated surgery for adhesive small bowel obstruction: a case report

Background An open abdomen with frozen adherent bowels is classified as grade 4 in Björck’s open abdomen classification, and skin grafting after wound granulation is a typical closure option. We achieved delayed primary fascia closure for a patient who developed open abdomen with enteroatmospheric fistulas due to severe adherent small bowel obstruction. We present here the details of his management. Case presentation A 52-year-old man suffered acute abdominal pain during a flight and received an emergency laparotomy due to adhesive small bowel obstruction. Repeated laparotomies were required, and later open abdomen and proximal site jejunostomy were selected. After negative pressure wound therapy, he was transferred to our institution. Two enteroatmospheric fistulas emerged on the exposed intestine, and we diagnosed the condition as a Björck grade 4 open abdomen. After 8 months of wound care and parenteral nutrition, we decided to attempt primary wound closure because the patient required permanent oral restriction and total parenteral nutrition due to short bowel syndrome. A circular incision along the circumference of the exposed bowel allowed us to take a safe approach into the abdominal cavity. We removed the intestinal adhesions completely and resected the bowels, including the fistulas and anastomosed parts. Finally, the abdominal wall defect was reconstructed using the component separation technique, and the patient was discharged without an ostomy. Conclusions Primary fascia closure for grade 4 open abdomen is hard, but leaving a long interval before radical surgery and applying pertinent wound management may help solve this adverse situation.

Clinicopathological and Molecular Characteristics of Colorectal Signet Ring Cell Carcinoma: A Review

Colorectal signet ring cell carcinoma (SRCC) is a rare subtype of colorectal cancer (CRC) with unique characteristics. Due to the limited researches on it, a comprehensive and in-depth understanding of this subtype is still lacking. In this article, we summarize the clinicopathological features and molecular characteristics of colorectal SRCC based on a literature review. Clinically, SRCC has been associated with young age, proximal site preference, advanced tumor stage, high histological grade, high rate of lymph node involvement, frequent peritoneal metastasis, and a significantly poor prognosis. Regarding molecular characteristics, in SRCC, the mutation burden of the classic signaling pathways that include WNT/β-catenin, RAS/RAF/MAPK, and PI3K/AKT/mTOR signaling pathways are generally reduced. In contrast, some genes related to the “epithelial-mesenchymal transition (EMT) process” and the “stem cell properties”, including RNF43, CDH1, and SMAD4, as well as the related TGF-β signaling pathway have been observed more frequently altered in SRCC than in conventional adenocarcinoma (AC). In many studies but not in others, SRCC showed a higher frequency of BRAF mutation, microsatellite instability-high (MSI-H) and CpG island methylator phenotype (CIMP) positive status compared to AC. It has been proposed that colorectal SRCC consists of two subtypes, in which the MSI+/CIMP+/BRAF+/CD3+/PD-L1+ hypermethylated genotype is more common in the proximal colon, and may represent the potential candidate for immunotherapy. Understanding the special molecular mechanisms related to the aggressive biology of SRCC is of great importance, which may provide a theoretical basis for the development of more targeted and effective treatments for this refractory disease.

Locus-associated R-loop repression in cis

R-loops exert varied beneficial or detrimental effects. To assess the function of an R-loop at a specific genetic locus, we had developed an inducible RNaseH1-EGFP-dCas9 (RED) protein chimaera as part of a locus-associated R-loop-modulating system (LasR). LasR is compatible with R-loop modulation in trans, which targets RED to one locus to repress R-loops at another spatially proximal site. Here we use the LasR system for R-loop modulation in cis, which consists of targeting RED directly to an R-loop. The combination of LasR in cis and trans will be essential to ascribe functions to specific R-loops within varied molecular contexts and study designs.

Dynamic Serosal Perfusion Assessment during Colorectal Resection Using Visible Light Spectroscopy

<b><i>Introduction:</i></b> Anastomotic leakage (AL) in colorectal surgery occurs with an incidence of up to 20%. Bowel perfusion is deemed to be one of the most important factors for anastomotic healing. However, not much is known about its variability during colorectal surgery and its impact on the outcome. Therefore, this study aims to evaluate serosal oxygen saturation patterns during colorectal resections with visible light spectroscopy (VLS). <b><i>Materials and Methods:</i></b> Bowel perfusion in patients undergoing left-sided colorectal resections was assessed at different timepoints during surgery using VLS on the colonic serosa. The primary outcome parameter was serosal oxygen saturation (StO₂) at the anastomosis during different timepoints of surgery. <b><i>Results:</i></b> We included 50 patients who underwent colorectal resection for bowel cancer (58%) and diverticular disease (34%). StO₂ at the proximal site of the anastomosis increased significantly throughout the surgery (mean difference 3.61%; 95% CI –6.22 to –1.00; <i>p</i> = 0.008). However, aberrancy from this identified perfusion pattern had no impact on the postoperative outcome. <b><i>Conclusion:</i></b> During colorectal resections, we could demonstrate an increase of the colonic StO₂ throughout surgery. Appearance of AL was not associated with lower StO₂, underlining the multifactorial genesis of developing AL.

A SARS CoV-2 nucleocapsid vaccine protects against distal viral dissemination

The SARS CoV-2 pandemic has killed millions of people. This viral infection can also result in substantial morbidity, including respiratory insufficiency and neurological manifestations, such as loss of smell and psychiatric diseases. Most SARS CoV-2 vaccines are based on the spike antigen, and although they have shown extraordinary efficacy at preventing severe lung disease and death, they do not always confer sterilizing immune protection. We performed studies in K18-hACE2 mice to evaluate whether the efficacy of SARS CoV-2 vaccines could be augmented by incorporating nucleocapsid as a vaccine antigen. We vaccinated mice with adenovirus-based vaccines encoding spike antigen alone, nucleocapsid antigen alone, or combined spike and nucleocapsid antigens. Mice were then challenged intranasally with SARS CoV-2, and acute viral loads were quantified at a proximal site of infection (lung) and a distal site of infection (brain). Interestingly, the spike-based vaccine conferred acute protection in the lung, but not in the brain. The spike-based vaccine conferred acute protection in the brain only if combined with the nucleocapsid-based vaccine. These findings suggest that nucleocapsid-specific immunity is important for the distal control of SARS CoV-2, warranting the inclusion of nucleocapsid in next-generation COVID-19 vaccines.

Re–Os and Sr Isotopic Study of Permian–Triassic Sedimentary Rocks from the Himalaya: Shale Chronology and Carbonate Diagenesis

Sedimentary rocks from the Himalayas are well-preserved archives of the Neo-Tethys oceanic conditions. In this contribution, Re–Os isotopic systematics of black shales from the Gungri Formation, Spiti valley and siltstones from the Khunamuh Formation, Guryul Ravine have been investigated to constrain their depositional ages. The Re–Os isochron for the Gungri shales yields a depositional age of 255 ± 22 Ma (2σ; n = 8; MSWD (Mean Square Weighted Deviation) = 5.7), consistent with available biostratigraphic information. The initial 187Os/188Os ratio (0.60 ± 0.13) is similar to that reported for the Late Permian shales, indicating the connection of the Neo-Tethys with the global ocean. In contrast, the Re–Os systematic is found to be non-isochronous for the Guryul Ravine section, a proximal site with a strong influence of seismic/Tsunami events. Global compilation of 187Re/188Os ratios in Late Permian shales and bathymetric distribution of the Re/Os ratios point to strong role of Re/Os uptake by macroalgae, in addition to oceanic pH and redox state, in regulating the Re–Os systematic in shales. The 87Sr/86Sr ratios for the Induan carbonates from the Spiti (0.71551–0.71837) are higher than to that expected for the Lower Triassic ocean (~0.707). Co-variations of Sr and 87Sr/86Sr with Mn concentrations establish the diagenetic alteration of these carbonates.

The provenance signal of climate–tectonic interactions in the evolving St. Elias orogen: framework component analysis and pyroxene and epidote single grain geochemistry of sediments from IODP 341 sites U1417 and U1418

The St. Elias orogen and the Surveyor Fan in the adjacent Gulf of Alaska are a coupled source to sink system recording the interplay of tectonics and variable degrees of glaciation during the collision of the Yakutat terrane with the southern Alaska margin since the Miocene. The Miocene to Holocene sediments of the Surveyor Fan were drilled during IODP expedition 341. The recovered material is used to constrain information on changes in erosion centers during the last 10 Ma to study the impact of climatic and tectonic processes on orogen evolution. Point counting of sand- and silt-sized light framework components and geochemical single grain analysis of heavy mineral groups epidote and pyroxene is applied to analyze patterns of sedimentary provenance of two sites on the distal and proximal Surveyor Fan (Site U1417 and U1418, respectively). The studied sands and silts of Miocene to Pleistocene age are slightly enriched in feldspar (plag >> kf) at the proximal site, compositions at both sites do not show systematical changes with time of deposition. Framework component spectra uniformly reflect the expected active margin provenance. Epidote and pyroxene compositions are very consistent and show no change with time of deposition. Associations of epidote and pyroxene with albite, titanite and pumpellyite are in line with near-shore sources in the Chugach Metamorphic Complex and the metabasite belt at its southern border, and in units of recycled detritus exposed in the fold and thrust belt on the western Yakutat Terrane, respectively. Rock fragments indicate input from mainly metamorphic sources during the Miocene and Pliocene and an increase of input from low-grade metamorphic and sedimentary rocks in the Pleistocene, a finding also indicated by the abundance of epidote and pyroxene. This implies increasing erosion of the near-shore areas of the fold and thrust belt with advance of glaciers to the shore since the Miocene, being enhanced by the onset of the Northern Hemisphere glaciation at the beginning of the Pleistocene. Climate changes connected to the mid-Pleistocene transition did not result in appreciable changes in the petrographic compositions. Glaciers seem to have remained nested in their topographically predefined positions, continuously feeding material with uniform characteristics into the fan.

A vulnerable, membrane-proximal site in human respiratory syncytial virus F revealed by a prefusion-specific single-domain antibody

Human respiratory syncytial virus (RSV) is a major cause of lower respiratory tract disease, especially in young children and the elderly. The fusion protein (F) exists in a pre- and postfusion conformation and is the main target of RSV-neutralizing antibodies. Highly potent RSV-neutralizing antibodies typically bind sites that are unique to the prefusion conformation of F. In this study we screened a single-domain antibody (VHH) library derived from a llama immunized with prefusion-stabilized F and identified a prefusion F-specific VHH that can neutralize RSV A at subnanomolar concentrations. Structural analysis revealed that this VHH primarily binds to antigenic site I while also making contacts with residues in antigenic site III and IV. This new VHH reveals a previously underappreciated membrane-proximal region sensitive for neutralization. Importance RSV is an important respiratory pathogen. This study describes a prefusion F-specific VHH that primarily binds to antigenic site I of RSV F. This is the first time that a prefusion F-specific antibody that binds this site is reported. In general, antibodies that bind to site I are poorly neutralizing, whereas the VHH described here neutralizes RSV A at subnanomolar concentrations. Our findings contribute to insights into the RSV F antigenic map.