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Enhanced synthesis of S-adenosyl-L-methionine through Combinatorial metabolic enginee...
Wenhan Xiao
Xiangliu Shi

Wenhan Xiao

and 10 more

March 09, 2024
S-Adenosyl-L-methionine (SAM) is a substrate for many enzyme-catalyzed reactions and provides methyl groups in numerous biological methylations, and thus has vast applications in the agriculture and medical field. Saccharomyces cerevisiae has been engineered as a platform with significant potential for producing SAM, although the current production has room for improvement. Thus, a method that consists of a series of metabolic engineering strategies was established this study. These strategies included enhancing SAM synthesis, increasing ATP supply, and down-regulating SAM metabolism and downregulating competing pathway. After combinatorial metabolic engineering, Bayesian optimization was conducted on the obtained strain C262P6 to optimize the fermentation medium. A final yield of 2972.8 mg/L at 36 h with 29.7% of the L-Met conversion rate in the shake flask was achieved, which was 26.3 times higher than that of its parent strain and the highest reported production in the shake flask to date. This paper establishes a feasible foundation for the construction of SAM-producing strains using metabolic engineering strategies and demonstrates the effectiveness of Bayesian optimization in optimizing fermentation medium to enhance the generation of SAM.
Evaluation of Physical and Mechanical Properties for Enhanced Thermal Insulation: An...
Philister Cheptepkeny Yator
David Njuguna Githinji

Philister Cheptepkeny Yator

and 3 more

March 09, 2024
This study explores the potential of fabricated clay bricks as effective thermal insulators for housing, with a focus on evaluating and enhancing key physical and mechanical properties. Employing clay soil and maize stalk biochar, a controlled approach identified optimal conditions for fabrication, resulting in notable improvements. The fabricated clay-biochar bricks exhibit a density of 1.418 g/cm 3, water absorption rate of 24.009%, thermal conductivity of 0.688 W/mK, and an impressive compressive strength of 8.408 N/mm. Biochar content, pressure, and temperature are identified as crucial factors in achieving these enhanced characteristics. These findings highlight the viability of clay-biochar bricks as sustainable and energy-efficient solutions for housing applications, meeting the demand for environmentally friendly construction materials with superior thermal insulation properties.
Drying and quality optimization of dried mango slices pretreated with low-cost anti-b...
Aaron Dzigbor
Courage Sedem Dzah

Aaron Dzigbor

and 4 more

March 09, 2024
The study sought to determine the effects of varying drying parameters on quality attributes and the effective diffusivity of dried mango slices treated with locally available anti­‑browning agent. To achieve this objective, sucrose solution of varying concentrations (40% w/v, 50% w/v, and 60% w/v) was prepared and mixed with lemon juice (20 mL). Mango slices were dipped in these sucrose-lemon juice solutions for varying osmotic times (30, 45, and 60 minutes) and were dried at different temperatures (50, 60, and 70°C). The effect of these treatments (sucrose concentration, osmotic times, and drying temperature) on colour, vitamin C content, and effective moisture diffusivity was determined, analysed, and optimized using the response surface methodology [[1]](#ref-0001). The optimum condition was found to be 60% w/v sucrose concentration, 50°C drying temperature, and 60 minutes of osmotic time. The predicted value for the responses under the optimum conditions was colour brightness value of 53 . 6786 , vitamin C content of 37 . 094   mg / 100 g with effective moisture diffusivity of 3 . 4449 × 10 - 9 m 2 / s . The results of the study indicate that immersion of mango slices in lemon juice prior to drying has the potential to retain vitamin C in the dried mango slices.
The Utility of Respiratory Rate Index in High-Flow Nasal Cannula Oxygen Therapy for C...
Kai Wang
Jihong Zhu

Kai Wang

and 6 more

March 09, 2024
A useful solution for the management of COVID-19 pneumonia has been identified: oxygen therapy delivered using a high-flow nasal cannula (HFNC). Improved oxygenation and respiratory support are provided by this treatment. In patients who are being associated with HFNC for COVID-19 pandemic, this investigation aims to define whether or not the respiratory rate index (RRI) is useful as an early indicator of how well the treatment is working and how the patient would fare clinically. This study retrospectively examines COVID-19 pneumonia patients maintained with HFNC in a clinical setting. Data on respiratory rate (RR) was used to calculate a respiratory rate index that considered both rate and pattern. Fast respiratory rate index reductions during the first therapy improved oxygenation and reduced mechanical ventilation. The score predicted pharmaceutical responsiveness before other clinical markers made meaningful improvements. RR, OSIXR, and ROX index are questionable ventilator prevention strategies. We treated 128 COVID-19 respiratory failure patients who needed oxygen. A 64 HFNC-treated patients were retrospectively studied. The HFNC group was those who converted from the HFNC therapy to conventional oxygen therapy (COT), while the COT treatment was those who converted from the HFNC group to Non-invasive ventilation (NIV). HFNC patients were successful (24 of 64 (62%)). HFNC success had a considerably greater univariate RR improvement than COT. Logistic regression analysis (LRA) adjusted for respiratory development, age, and ROX index >6.66 showed that an enhanced RR predicted success. HFNC achievement groups had significantly lower COT durations than COT groups.
Combining computer-based rehabilitative approach with tDCS for recovering of aphasia:...
Marianna Contrada
Federica Scarfone

Marianna Contrada

and 9 more

March 09, 2024
Combining computer-based rehabilitative approach with tDCS for recovering of aphasia: implications from a single case studyMarianna Contrada 1, Federica Scarfone1, Antonella Iozzi1, Simone Carozzo1, Martina Vatrano1, Maria Grazia Nicoletta1, Giuseppe Nudo1, Maria Quintieri1, Paolo Tonin1, Antonio Cerasa1,2,3*1 S’Anna Institute, 88900 Crotone, Italy2 Institute for Biomedical Research and Innovation (IRIB), National Research Council of Italy (CNR), 98164, Messina, Italy3 Pharmacotechnology Documentation and Transfer Unit, Preclinical and Translational Pharmacology, Department of Pharmacy, Health Science and Nutrition, University of Calabria, 87036 Rende, ItalyPrimary Text Words Count: 1800Keywords: Aphasia; tDCS; VRRS cognitive treatment; stroke; language comprehension.
Neuroprotective effects of resveratrol on retinal ganglion cells in glaucoma: Focusin...
Maryam   Golmohammadi
Seyed Arash  Aghaei Meibodi

Maryam Golmohammadi

and 8 more

March 09, 2024
Retinal ganglion cells (RGCs) are the major cells that are damaged in glaucoma leading to vision loss and blindness. The damage to RGCs in glaucoma is caused by various mechanisms such as elevated intraocular pressure, oxidative stress, inflammation, and other neurodegenerative processes. As the disease progresses, more and more RGCs are lost, leading to a gradual loss of vision. Therefore, protecting RGCs from damage and promoting their survival is an important goal in the treatment of glaucoma. Resveratrol (RES) exerts anti-oxidant effects and slows down the evolution and progression of glaucoma. This review was prepared using databases such as Google Scholar, PubMed, Scopus, and ScienceDirect. Based on the findings of this review, RES has a protective role on RGCs in cases of ischemic injury and hypoxia as well as ErbB2 protein expression in the retina. Additionally, RES has protective effects on RGCs by promoting cell growth, reducing apoptosis, and decreasing oxidative stress in H2O2-exposed RGCs. RES was also found to inhibit oxidative stress damage in RGCs and suppress the activation of MAPK signaling pathways. Moreover, RES could alleviate retinal function impairment by suppressing the HIF-1a/VEGF and p38/p53 axis while stimulating the PI3K/Akt pathway. Hence, RES might exert potential therapeutic effects in the treatment of glaucoma by protecting RGCs from damage and promoting their survival.
Photosynthesis and photoprotection in top leaves respond faster to irradiance fluctua...
Bingjie Shao
Yuqi Zhang

Bingjie Shao

and 6 more

March 09, 2024
Accounting for the dynamic responses of photosynthesis and photoprotection to naturally fluctuating irradiance can improve predictions of plant performance in the field, but the variation of these dynamics within crop canopies is poorly understood. We conducted a detailed study of dynamic and steady-state photosynthesis, photoprotection, leaf pigmentation, and stomatal anatomy in four leaf layers (100, 150, 200 and 250 cm from the floor) of a fully-grown tomato canopy in the greenhouse. We found that leaves at the top of the canopy exhibited higher photosynthetic capacity and faster photosynthetic induction (shorter time to reach 50% of full photosynthetic induction; t50-A) compared to lower-canopy leaves, accompanied by higher stomatal conductance and a faster activation of carboxylation and linear electron transport capacities. In upper-canopy leaves, non-photochemical quenching showed faster induction and relaxation after in- and decreases in irradiance, allowing for more effective photoprotection in these leaves. A large number of leaf functional traits, including photosynthetic capacity, chlorophyll a: b ratio, stomatal density and specific leaf area, correlated strongly with the irradiance integral and the red:far-red ratio, both of which showed strong gradients throughout the canopy. The rate of stomatal movement after in- or decreases in irradiance was not strongly affected by leaf layer, and neither was the rate of loss of photosynthetic induction under low irradiance. Time-averaged photosynthesis under fluctuating irradiance was strongly correlated to steady-state photosynthesis under high irradiance, and to a lesser extent to t50-A, suggesting that both steady-state photosynthetic capacity and the rapidity of photosynthesis response to a change in irradiance affect time-integrated dynamic photosynthesis.
Two cases of AMeD syndrome with isochromosome 1q treated with allogeneic stem cell tr...
Mari Kagajo
Kyoko Moritani

Mari Kagajo

and 9 more

March 09, 2024
AMeD syndrome is characterized by aplastic anemia, mental retardation, short stature, and microcephaly and is caused by digenic mutations in the aldehyde dehydrogenase 2 ( ALDH2) and alcohol dehydrogenase 5 ( ADH5) genes. We have successfully performed hematopoietic stem cell transplantation in two patients with AMeD syndrome and isochromosome 1q. AMeD syndrome with myelodysplastic syndrome or acute myeloblastic leukemia generally has a poor prognosis; however, early diagnosis may improve treatment response. Although the gain of 1q has been considered as a form of early clonal evolution in Fanconi anemia, it may be an equally important finding observed in AMeD syndrome.
Bernard-Soulier syndrome caused by a novel GP1BB variant and 22q11.2 deletion
Rintaro Nagoshi
Atsushi Sakamoto

Rintaro Nagoshi

and 6 more

March 09, 2024
Bernard-Soulier syndrome (BSS) is caused by defects in GP1BA, GP1BB, or GP9 genes. Patients with 22q11.2 deletion syndrome (22q11.2DS) are obligate carriers for BSS because GP1BB resides on chromosome 22q11.2. A 15-month-old girl without bleeding symptoms had giant platelets and thrombocytopenia. Physical findings and macrothrombocytopenia suggested 22q11.2DS, which was confirmed by fluorescence in situ hybridization. Flow-cytometry showed decreased GPIbα on the platelets. A novel variant in GP1BB, p.(Val169_Leu172del), was revealed by gene panel testing. These findings confirmed that she had BSS. This case suggests that any 22q11.2DS patient associated with macrothrombocytopenia should be further investigated for the presence of BSS.
The Effect of ABO Blood Group Incompatibility on Hematopoietic Stem Cell Transplantat...
Zuofeng Li
hao xiong

Zuofeng Li

and 7 more

March 09, 2024
The influence of ABO incompatibility on transplant results in juvenile aplastic anemia (SAA) children receiving hematopoietic stem cell transplantation (HSCT) is debated, and no published data are available. This study involved 85 children with AA who received hematopoietic stem cell transplants from donors who were ABO-compatible (n = 38), major ABO-incompatible (n = 17), minor ABO-incompatible (n = 21), and bi-directionally incompatible (n = 9). Except for a statistical difference in acute graft-versus-host disease (aGVHD), the four groups did not have significantly different chronic GVHD, overall survival, and neutrophil and platelet implantation rates, and no pure red cell aplasia or passenger lymphocyte syndrome. Therefore, we inferred that ABO blood group-incompatible donors do not significantly affect HSCT outcomes and are not a barrier.
Phytotherapy and anthroposophic medicine as a treatment option for bronchial asthma:...
Céline Braunwalder
Jana Ertl

Céline Braunwalder

and 4 more

March 09, 2024
Bronchial asthma is a highly prevalent health condition associated with low quality of life and high economic costs. Treatments from traditional, complementary and integrative medicine (TCIM) are commonly used by individuals with bronchial asthma. However, a synthesis of the evidence on plant-derived medication is lacking. This review aims to systematically summarize the evidence on the efficacy, effectiveness and safety of European/Western phytotherapy (PT) and medications from anthroposophic medicine (AM) in individuals with bronchial asthma. Four electronic databases and additional references were screened for clinical trials published between 1990 and 2023. The findings of the included studies were qualitatively synthesized and study quality was assessed. Of 23 included studies, 19 examined European/Western PT and four investigated AM medications. Nine studies of sufficient quality reported beneficial effects of various plants (e.g., Nigella sativa) on asthma symptoms, pulmonary function and immunological parameters. The medications were considered safe in studies that reported on safety. Overall, this systematic review suggests several medications from European/Western PT and AM that may be beneficial and appear to be safe in the treatment of bronchial asthma. However, further rigorous studies are needed to provide evidence-based guidance on additional treatment options for individuals with bronchial asthma.
Advancing the allergenicity assessment of new proteins using a text mining resource
F. Javier Moreno
Jorge Novoa

F. Javier Moreno

and 4 more

March 09, 2024
BACKGROUND: With a society increasingly demanding alternative protein food sources, new strategies for evaluating protein safety issues, such as their allergenic potential, are needed. Large-scale and systemic studies on allergenic proteins are hindered by the limited and non-harmonized clinical information available for these substances in dedicated databases. A clearly missing key information is that representing the symptomatology of the allergens, especially given in terms of standard vocabularies, that would allow connecting with other biomedical resources to carry out different studies related to human health. In this work, we have generated the first resource with a comprehensive annotation of allergens’ symptomatology, using a text-mining approach that extracts significant co-mentions between these entities from the scientific literature. METHODS: The main resource of biomedical literature (PubMed, ~36 million abstracts) was mined to automatically extract relationships between allergens and clinical symptoms. The annotations are given in terms of standard vocabularies in widely used biomedical databases. The method identifies statistically significant co-mentions between the textual descriptions of the two types of entities in the literature as indication of relationship. RESULTS: 1,180 clinical signs extracted from the Human Phenotype Ontology (HPO), the Medical Subject Heading (MeSH) terms of PubMed together with other allergen-specific symptoms, were linked to 1,036 unique allergens annotated in the two main allergen-related public databases via 14,009 relationships. CONCLUSIONS: This resource could serve as a starting point for a future manually curated compilation of allergen symptomatology. The annotations are publicly available through an interactive web interface at [https://csbg.cnb.csic.es/CoMent_allergen/](https://csbg.cnb.csic.es/CoMent_allergen/).
Association Between Proactive Esophageal Cooling and Increased Lab Throughput
William Zagrodzky
Julie Cooper

William Zagrodzky

and 16 more

March 09, 2024
Introduction: Proactive esophageal cooling has been FDA cleared to reduce the likelihood of ablation-related esophageal injury resulting from radiofrequency (RF) cardiac ablation procedures. Data suggest that procedure times for RF pulmonary vein isolation (PVI) also decrease when proactive esophageal cooling is employed instead of luminal esophageal temperature (LET) monitoring. Reduced procedure times may allow increased electrophysiology (EP) lab throughput. We aimed to quantify the change in EP lab throughput of PVI cases after the introduction of proactive esophageal cooling. Methods: EP lab throughput data were obtained from three electrophysiology groups. We then compared EP lab throughput over equal time frames at each site before (pre-adoption) and after (post-adoption) the adoption of proactive esophageal cooling. Results: Over the time frame of the study, a total of 2,498 PVIs were performed over a combined 74 months, with cooling adopted in September 2021, November 2021 and March 2022 at each respective site. In the pre-adoption time frame, 1,026 PVIs were performed using a combination of LET monitoring with the addition of esophageal deviation when deemed necessary by the operator. In the post-adoption time frame, 1,472 PVIs were performed using exclusively proactive esophageal cooling, representing a mean 43% increase in throughput (p < 0.0001), despite the loss of two operators during the post-adoption time frame. Conclusion: Adoption of proactive esophageal cooling during PVI ablation procedures is associated with a significant increase in EP lab throughput, even after a reduction in total number of operating physicians in the post-adoption group.
Impatiens pseudolenta (Balsaminaceae), A new species from southern part of Western Gh...
Satheshkumar C
Diksha Kumari

Satheshkumar C

and 4 more

March 09, 2024
The genus Impatiens Linnaeus (1753: 937) belongs to the family Balsaminaceae and comprises of about 1107 accepted species all over the world (POWO 2024). The genus is mainly distributed to south-east Asia, tropical Africa and Madagascar (Yu 2012). In India, the genus Impatiens consists of 340 taxa (314 species and 26 varieties/subspecies), mainly distributed in the Eastern Himalayas, the neighbouring North-Eastern states and the Western Ghats (Prabhukumar et al. 2022, Borah et al. 2022, Richard & Ravichandran, 2023, Khanal et al. 2023, Tiwari 2023).
Bioengineer mesenchymal stem cell for Treatment of glioma by IL-12 mediated microenvi...
Man Li
Lisen Lu

Man Li

and 8 more

March 09, 2024
High expression of cellular self-activated immunosuppressive molecules and extensive infiltration of suppressive immune cells in the tumor microenvironment are the main factors leading to the resistance of glioma to immunotherapy. However, the technology related to modifying the expression of glioma cellular self-molecules based on gene editing still needs to be developed. In this project, cell therapy strategies were developed to reverse the immunosuppressive microenvironment of glioma (TIME). Mesenchymal stem cells (MSCs) derived from bone marrow were used as carriers to express bioactive proteins, which could exhibit tumor-homing characteristics in response to tumor TGF-β signals. MSCs were modified to express the secretory anti-tumor immune cytokine IL-12 and the nCD47-SLAMF7 fusion protein, which regulates the phagocytosis of macrophages. The engineered MSCs are then injected in situ into the area near the glioma to bypass the blood-brain barrier and provide localized high concentrations of bioactive proteins. This approach could significantly activate natural and adaptive immune cells in the TIME, ultimately leading to the effective control of glioma. This study provides a new strategy for the clinical treatment of glioma patients and the prevention of postoperative recurrence.
Residence time distribution in continuous virus filtration
Alois Jungbauer
Yu-Cheng Chen

Alois Jungbauer

and 4 more

March 09, 2024
Regulatory authorities recommend using residence time distribution (RTD) to address material traceability in continuous manufacturing. Continuous virus filtration is an essential but poorly understood step in biologics manufacturing. Here we describe a model that considers non-ideal mixing and film resistance for RTD prediction in continuous virus filtration, and its experimental validation using the inert tracer NaNO 3. The model was successfully calibrated through pulse injection experiments, yielding good agreement between model prediction and experiment ( R 2 >   0.90). The model enables prediction of RTD with variations—e.g., in injection volumes, flow rates, tracer concentrations, and filter surface areas—and was validated using stepwise experiments, and combined stepwise and pulse injection experiments. All validation experiments achieved R 2 >   0.97, except when valves were switched at a high flow rate. Notably, if the process includes a porous material—such as a porous chromatography material, ultrafilter, or virus filter—it must be considered whether the molecule size affects the RTD, as tracers with different sizes may penetrate the pore space differently. Calibration of the model with NaNO 3 enabled extrapolation to RTD of recombinant antibodies, which will promote significant savings in antibody consumption. This RTD model is ready for further application in end-to-end integrated continuous downstream processes, such as addressing material traceability during continuous virus filtration processes.
Targeting STAT3 Signaling Pathway by Curcumin and Its analogues for Breast Cancer: An...
Mohammad Yassin Zamanian
Maryam   Golmohammadi

Mohammad Yassin Zamanian

and 9 more

March 09, 2024
Breast cancer (BC) has emerged as the fifth most prevalent cause of cancer-related morbidity, prompting considerable interest from researchers due to its increased malignancy and resistance to drugs. Traditional chemotherapy methods have demonstrated limited effectiveness in treating all BC subtypes, underscoring the pressing demand for innovative therapeutic strategies or medications. Curcumin, a bioactive substance extracted from Curcuma longa, has been widely examined for its potential as an oncology drug. Research indicates that turmeric extract and its derivatives effectively inhibit STAT3, resulting in downstream effects like reducing cancer cell growth, triggering cell death, and preventing metastasis. The research on curcumin’s impact on the STAT3 pathway in BC demonstrated that curcumin effectively inhibits STAT3, leading to downstream effects such as the downregulation of Bcl-xL, Bcl-2, and Survivin, and the induction of apoptosis in H-Ras MCF10A cells. Additionally, it showed curcumin’s ability to hinder proliferation and anchorage-independent cell growth. The research also examined the effects of curcumin derivatives, like FLLL11, FLLL12, hydrazinocurcumin (HC), and GO-Y030, on STAT3 inhibition and their potential as therapeutic agents for BC. Observed results indicated the promise of curcumin and its derivatives in targeting the STAT3 signaling pathway for BC therapy.
“Dead birds flying”: Can North American rehabilitated raptors released into the wild...
Christian Hagen
John Goodell

Christian Hagen

and 3 more

March 09, 2024
As the human footprint expands to meet societal energy needs, as do the impacts to wildlife. Raptors in particular are highly susceptible to anthropogenic caused mortality. Industry sectors are encouraged to offset these causes of mortality. Several options to mitigate these losses have been proposed, including raptor rehabilitation. However, its role as a conservation tool is untested. Currently no peer-reviewed demographic analyses exists using post-release data from rehabilitated raptors to evaluate its effectiveness at continental scales. Our objectives were to estimate annual survival of rehabilitated and wild raptors, impute those estimates into demographic models to assess potential effects at individual and population levels. We hypothesized that rehabilitated raptors would survive similarly to their wild counterparts after an acclimation period, and that longer-lived species (K-selected) would benefit most from these releases. We used U.S. Geological Survey Bird Banding Lab band-recovery data (1974 – 2018) from 20 raptor species for modeling survival of rehabilitated individuals (n = 125,740) in comparison to wild birds (n = 1,913,352). Results from 17 species with adequate recovery data indicated that 5 species ≠ wild survival, 2 species had uncertain estimates, and 10 species ≈ wild survival by years 2 and 3 post-release. We acquired admissions (n = 69,707) and release (n = 25,740) data from 24 rehabilitation centers across the U.S. (2012-2021). We imputed survival, fecundity and numbers of releases into demographic models. These models quantified the extent to which rehabilitated raptors may contribute to broader conservation efforts, especially in the context of individual take. All but two species, had measurable numbers of individuals added to populations regardless of the number of releases. The general pattern was for K-selected species to yield larger benefits from rehabilitated supplementation to the population. Combined these results provide evidence that rehabilitation may serve as mitigation tool to offset incidental take
Metal-free Electrochemical Trifluoromethylation of Imidazole-Fused Heterocycles with...
Chang Ge
Lipeng  Qiao

Chang Ge

and 8 more

March 09, 2024
A novel and eco-friendly electrochemical activation of trifluoromethyl thianthrenium triflate (TT–CF3+OTf−) for trifluoromethylation of imidazole-fused heteroaromatic compounds was established. This method involves the direct electrolysis of TT–CF3+OTf− without the requirement of external oxidants or catalysts, aligning with the principles of green chemistry. A wide range of imidazole-fused heteroaromatic compounds including imidazo[1,2-a]pyridines and benzo[d]imidazo[2,1-b]thiazoles have been successfully trifluoromethylated using this technique, exhibiting excellent compatibility with various functional groups and a broad substrate scope. Moreover, the method’s applicability for one-pot sequential reactions enables the reduction of waste and resource consumption by eliminating the need for intermediate purification steps.
Ruthenium-Catalysed Asymmetric Intramolecular Isomerization/Esterification Reaction:...
Lingzi Zhao
Xuchao Wang

Lingzi Zhao

and 6 more

March 09, 2024
An asymmetric isomerization/intramolecular coupling reaction of allylic alcohols to synthesize chiral dihydrocoumarins was suc-cessfully accomplished through ruthenium catalysis. This method demonstrates a wide substrate applicability, excellent tolerance for various functional groups, and good enantioselectivities (up to 90% ee). It provides a convenient pathway to produce a diverse range of structurally distinct chiral dihydrocoumarins in good efficiency.
Should we use risk selection tests for HPV 16 and/or 18 positive cases: comparison of...
Karolina Mazurec
Martyna  Trzeszcz

Karolina Mazurec

and 5 more

March 09, 2024
Background: Major screening abnormalities in pre-colposcopic stage are tests results that imply direct referral to colposcopy (and/or expedited treatment) without performing additional high-grade squamous intraepithelial lesions or worse (HSIL+) risk selection testing. Currently, both clinically validated HSIL+ risk selection tests, reflex cytology and reflex p16/Ki67 dual staining (DS), are being compared for use in primary HPV-based screening to avoid possible overtreatment, but there is still no sufficient data available for their performance. Methods: Among 30,066 liquid-based cervical cancer screening tests results, a group of 332 women was selected with available HRHPV tests results with 16/18 limited genotyping, liquid-based cytology, DS, and histology results from standardized colposcopy with biopsy. In HPV 16/18+ cases, three triage approaches were retrospectively analyzed. Predictive values for detection of HSIL+ were calculated and number of colposcopies required in each strategy. Results: Both triage models with DS used (reflex cytology followed by DS, and reflex DS alone in all cases) had significantly higher PPV for HSIL+ than strategy with reflex cytology alone (44.2%/45.7% vs. 28.3%; p<0.0001). In models with DS, less colposcopies were required (95/92 vs. 152) and less colposcopies were needed per HSIL+ detection (2,26/2,19 vs. 3,54). Only 1 HSIL+ case was missed in both triage models with DS incorporation. Conclusions: p16/Ki67 dual-stain may be an effective, alone or combined with cytology, triage test to detect HSIL+ in patients with major screening abnormalities in primary HPV-based cervical cancer screening. Performing cytology as the first triage test improves the strategy by enabling referrals to expedited treatment in selected cases.
Mechanistic studies on rhodium-catalyzed chemo-selective cy-cloaddition of ene-vinyli...
ZiQi  Yu
Min Shi

ZiQi Yu

and 2 more

March 09, 2024
Rhodium-catalyzed cycloaddition reactions are a powerful tool for the construction of polycyclic compounds. Experimental combined with DFT studies were used to investigate the temperature-controlled chemoselectivity of cationic rhodium-catalyzed intramolecular cycloaddition reactions of ene-vinylidenecyclopropanes. After a series of mechanistic studies, it was found that trace amount of water in the reaction system play an important role for generating endo-double bond product and revealed that trace amount of water in the reaction system including the rhodium catalyst, substrate and solvent were enough to promote the formation of endo-double bond product, and additional water could not further accelerate the reaction. DFT calculation results show that the addition of water indeed significantly lowers the energy barrier of proton transfer step, making the formation of endo-double bond product more likely to occur and confirmed the rationality of water-assisted proton transfer occurring in the selective access to endo-double bond product.
Causes and consequences of divorce in a long-lived socially monogamous bird
Frigg Speelman
Terry Burke

Frigg Speelman

and 4 more

March 09, 2024
In socially monogamous species, sexual selection not only depends on initial mate choice but also mate switching. To date, studies lack assessment of differences between passive (widowhood) and active (divorce) mate switching, longer-term fitness consequences, and how age masks reproductive costs and benefits of divorce. We investigated causes and long-term consequences of divorce and their age-dependence using longitudinal data on Seychelles warblers (Acrocephalus sechellensis), and experimentally test for short-term effects of mate-switching. Young and old males, but not females, divorced most frequently. Divorce propensity declined with pair bond duration and reproductive success in both sexes, but mate switching did not result in short-term costs. Divorcees did not gain short- or long-term fitness benefits compared to non-divorcees. In fact, female early-life divorcees that lost their breeding position had lower survival than females that never divorced. Divorce is likely a strategy to escape poor-quality partnerships, but not all divorcees benefit from divorcing.
Parts of a whole: isotopic offset between single keratin-based tissues and whole-body...
K.R. Davis
Hannah  Vander Zanden

K.R. Davis

and 1 more

March 08, 2024
Abstract RATIONALE Stable isotope analysis is a frequently used tool in ecology for unraveling dietary dynamics and trophic relationships. In isotopic studies that use mixing models to infer diet, a single tissue is often used to represent the isotopic values of a whole organism. Here, we examine that assumption in keratin-based tissues and provide recommendations for isotopic diet studies of animals that consume prey whole. METHODS By comparing carbon ( δ 13C) and nitrogen ( δ 15N) stable isotope values in single tissues of mammals and birds, this study aims to elucidate the extent to which nondestructive sampling methods in tissues such as hair and feathers, accurately represent the overall isotopic composition of four mammalian species (rats, mice, rabbits, guinea pigs) and one avian species (quail). RESULTS We found that keratin-based tissue and the homogenized whole-body samples were significantly different in δ 13C values in mammals (mean 𝚫 13C -1.93 ± 0.37‰) but not in birds. Feathers differed significantly from whole body in δ 15N values in birds (mean 𝚫 15N -0.32 ± 0.11‰), but δ 15N values did not differ among hair and the whole body of mammals. CONCLUSIONS We provide a mathematical correction for diet reconstruction based on specific tissues, especially for animals consuming whole prey. We suggest that future studies reconsider the assumption that non-invasively sampled tissues are representative of whole-body isotopic values.
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