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Abstract Recombinant human brain natriuretic peptide (rhBNP) effects on type 4 cardiorenal syndrome (CRS) and adverse events such as heart failure rehospitalization and all-cause mortality have not been assessed in large-scale research. This study evaluated the impact of rhBNP on emergency dialysis and prognosis in end-stage renal disease (ESRD) patients with type 4 CRS, and the risk factors of emergency dialysis. This retrospective cohort study included patients with type 4 CRS and ESRD admitted for decompensated heart failure between January 2016 and December 2021. Patients were divided into the rhBNP and non-rhBNP cohorts, according to whether they were prescribed rhBNP. The primary outcomes were emergency dialysis at first admission and cardiovascular events within a month after discharge. A total of 77 patients were included in the rhBNP cohort (49 males and 28 females, median age 67) and 79 in the non-rhBNP cohort (47 males and 32 females, median age 68). After adjusting for age, residual renal function, and primary diseases, Cox regression analysis showed that rhBNP was associated with emergency dialysis (HR = 0.633, 95% CI 0.420–0.953) and cardiovascular events (HR = 0.410, 95% CI 0.159–0.958). In addition, multivariate logistic regression analysis showed that estimated glomerular filtration rate (eGFR) (OR = 0.782, 95% CI 0.667–0.917, P = 0.002) and procalcitonin (PCT) levels (OR = 1.788, 95% CI 1.193–2.680, P = 0.005) at the first visit were independent risk factors for emergency dialysis while using rhBNP was a protective factor for emergency dialysis (OR = 0.195, 95% CI 0.084–0.451, P

Ethnopharmacological relevance: Pelvic inflammatory disease (PID) is a frequently occurring gynecological disorder mainly caused by the inflammation of a woman’s upper genital tract. Generally, antibiotics are used for treating PID, but prolonged use poses potential risks of gut bacterial imbalance, bacterial resistance, super bacteria production, and associated adverse reactions. Traditional Chinese medicine (TCM) has shown unique advantages in various ailments and has received widespread clinical research attention. Fuke Qianjin (FUKE) capsule is an approved National Medical Products Administration (NMPA License No. Z20020024) Chinese herbal prescription that has been widely used individually or in combination with other Western medicines for the treatment of various gynecological inflammatory diseases, including chronic cervicitis, endometritis, and chronic PID.Aim: This clinical trial was designed to assess the safety and efficacy of FUKE capsule in mild-to-moderate symptomatic PID patients.Materials and methods: This phase 2, randomized, double-blind, positive controlled clinical trial was conducted in mild-to-moderate symptomatic PID patients at a single center in Pakistan from 21 September 2021 to 11 March 2022. Eligible female participants were randomly assigned to a test and a control group with a ratio of 1:1. The test group subjects received two metronidazole (METRO) tablets and one doxycycline hyclate (DOXY) simulant at a time, twice daily for 14 days, and two Fuke Qianjin (FUKE) capsules, three times a day after a meal for 28 days. Subjects in the control group received two METRO tablets and one DOXY tablet at a time, twice daily for 14 days, and two FUKE simulant capsules, three times a day after meal for 28 days. The primary efficacy outcome was an improvement in pelvic pain symptoms assessed through a visual analog scale (VAS). The secondary outcomes were the improvement in secondary efficacy symptoms like local physical signs, clinical assessment of leucorrhea and cervical secretions through laboratory examination, and improvement in the maximum area of pelvic effusion assessed through gynecological ultrasound after the treatment. The safety outcomes were assessed through vital signs, laboratory tests, electrocardiogram findings, and adverse events/serious adverse events.Results: A total of 198 subjects with active PID were randomly assigned to a test group (n = 99) and a control group (n = 99). The baseline characteristics of the subjects in the two groups were similar. In the intention-to-treat analysis, the primary efficacy was 84.9% for the test group and 71.6% for the control group, with a statistically significant difference (p = 0.0370; 95% CI −0.2568 to −0.0088). The secondary clinical efficacy was 88.4% for the test group and 82.7% for the control group, with no significant difference (p = 0.2977; 95% CI −0.1632 to 0.0501). The improvement in local physical signs was 95.8% for the test group and 76.9% for the control group, with no significant difference (p = 0.0542; 95% CI −0.3697 to −0.0085). The inter-group non-inferiority comparison showed that the upper limit of the 95% CI was less than 0.15 and thus met the non-inferiority requirements of the test group to the control group. The results of clinical signs of leucorrhea and cervical secretions showed that there was no difference in the rate of improvement between the test and control groups, indicating that FUKE was non-inferior to DOXY. A total of 14 adverse events in eight subjects were observed in the trial, with an incidence rate of 4.7%. Four subjects in each group experienced seven adverse events with 4.5% and 4.8% incidence rates of adverse reactions in the test and control groups, with no statistically significant differences (p = 0.2001). No serious adverse events occurred in the trial.Conclusion: The results of this trial indicate that the test drug (Fuke Qianjin capsule) is non-inferior to the control drug (doxycycline hyclate tablet) in treating mild-to-moderate PID patients with comparable efficacy, safety, and tolerability to the control drug.Clinical Trial Registration:www.clinicaltrials.gov, identifier NCT04723069.

Abstract Background Patients who undergo gastrointestinal endoscopy often require propofol-based sedation combined with analgesics. At present, the efficacy and safety of esketamine as an adjunct to propofol for sedation during endoscopic procedures in patients remains controversial. Moreover, there is no universal agreement regarding the appropriate dose of esketamine supplementation. This study aimed to assess the efficacy and safety of esketamine as an adjunct to propofol for sedation during endoscopic procedures in patients. Methods Seven electronic databases and three clinical trial registry platforms were searched and the deadline was February 2023. Randomized controlled trials (RCTs) evaluating the efficacy of esketamine for sedation were included by two reviewers. Data from the eligible studies were combined to calculate the pooled risk ratio or standardized mean difference. Results Eighteen studies with 1962 esketamine participants were included in the analysis. As an adjunct to propofol, the administration of esketamine reduced the recovery time compared to normal saline (NS). However, there was no significant difference between the opioids group and ketamine group. For propofol dosage, the administration of esketamine required a lower propofol dosage compared to the NS group and opioids group].For complications, the esketamine group had fewer complications compared to the NS group and opioid group in patients, but there were no significant differences between the esketamine group and ketamine group. Notably, the coadministration of esketamine was associated with a higher risk of visual disturbance compared to the NS group. In addition, we used subgroup analysis to investigate whether 0.2–0.5 mg/kg esketamine was effective and tolerable for patients. Conclusion Esketamine as an adjunct to propofol, is an appropriate effective alternative for sedation in participants undergoing gastrointestinal endoscopy. However, considering the possibility of its psychotomimetic effects, esketamine should be used with caution.

Abstract Background Plant shape and structure are important factors in peanut breeding research. Constructing a three-dimension (3D) model can provide an effective digital tool for comprehensive and quantitative analysis of peanut plant structure. Fast and accurate are always the goals of the plant 3D model reconstruction research. Results We proposed a 3D reconstruction method based on dual RGB-D cameras for the peanut plant 3D model quickly and accurately. The two Kinect v2 were mirror symmetry placed on both sides of the peanut plant, and the point cloud data obtained were filtered twice to remove noise interference. After rotation and translation based on the corresponding geometric relationship, the point cloud acquired by the two Kinect v2 was converted to the same coordinate system and spliced into the 3D structure of the peanut plant. The experiment was conducted at various growth stages based on twenty potted peanuts. The plant traits’ height, width, length, and volume were calculated through the reconstructed 3D models, and manual measurement was also carried out during the experiment processing. The accuracy of the 3D model was evaluated through a synthetic coefficient, which was generated by calculating the average accuracy of the four traits. The test result showed that the average accuracy of the reconstructed peanut plant 3D model by this method is 93.42%. A comparative experiment with the iterative closest point (ICP) algorithm, a widely used 3D modeling algorithm, was additionally implemented to test the rapidity of this method. The test result shows that the proposed method is 2.54 times faster with approximated accuracy compared to the ICP method. Conclusions The reconstruction method for the 3D model of the peanut plant described in this paper is capable of rapidly and accurately establishing a 3D model of the peanut plant while also meeting the modeling requirements for other species' breeding processes. This study offers a potential tool to further explore the 3D model for improving traits and agronomic qualities of plants.

In this paper, the problem of energy planning in energy network is studied, and an energy optimal scheduling strategy and a dynamic two-layer distributed cooperative control method are proposed. First of all, in the upper layer, the optimal scheduling model of primary energy including renewable energy is designed, and the thermal inertia of heat load is taken into account, which reduces the cost of energy supply, improves the consumption of new energy and promotes carbon neutralization, so that the micro-energy network can operate economically and environmentally friendly. From the point of view of automatic generation control (AGC), the lower layer uses Linear Quadratic Gaussian (LQG) to realize the real-time control of single-area AGC units and ensure the stable operation of the network. Secondly, according to the control deviation of each area, a dynamic stratification strategy is designed, which can not only ensure the effect, but also save resources.

Inonotus obliquus is anatural plant fungal resource with a variety of biological activities. Triterpenoids are the main functional components. Because triterpenoids have excellent anticancer, hypoglycemic and antioxidant properties, the related research and development has attracted much attention in recent years. In this paper, the current research status of Inonotus obliquus triterpenoid compounds are summarized and analyzed from the aspects of induction fermentation production, separation and purification of sporophore triterpenoid compounds, chemical composition and structure analysis, functional characteristics and application development, among which the use of plant commensal microbial extracts as inducers in induction fermentation production is the most significant. The separation and purification techniques have respective advantages according to different purposes. The separation and purification technologies with high separation efficiency such as high-performance counter-current chromatography and high-performance liquid chromatography are more suitable for chemical composition and structure analysis, and macroporous resin has more advantages in large-scale application. Based on the above analysis, the future research direction is prospected, which provides a theoretical basis for subsequent development and research and application in that medicine and food industry.

Apple bitter rot is a serious agricultural disease caused by Colletotrichum gloeosporioides. In recent years, carbendazim-resistant C. gloeosporioides strains bearing an E198A point mutation in the β-tubulin gene (GAG to GCG) have emerged, threatening global apple production. As such, rapidly detecting the presence of this E198A mutation in C. gloeosporioides isolates is essential in order to monitor the spread of this pathogen and to prevent outbreaks of disease. Herein, we developed a simple loop-mediated isothermal amplification (LAMP) approach to detecting the E198A mutation in C. gloeosporioides isolates from ‘Gala’ apple samples. This optimized LAMP protocol was sufficient to establish the E198A genotype of a given isolate following a 60 min incubation at 63 °C by using four specific primers. The results of this reaction could be interpreted visually based on a fluorescent yellow-green color change upon the addition of the SYBR Green I dye, and were additionally confirmed via gel electrophoresis. Importantly, this LAMP assay was capable of rapidly and reliably detecting apples that were infected with carbendazim-resistant isolates harboring this E198A mutation. In conclusion, this LAMP assay in this study can rapidly, specifically, and sensitively detect cases of apple bitter rot caused by C. gloeosporioides isolates harboring the E198A mutation.

Three-dimensional (3D) matrix models using hydrogels are powerful tools to understand and predict cell behavior. The interactions between the cell and its matrix, however is highly complex: the matrix has a profound effect on basic cell functions but simultaneously, cells are able to actively manipulate the matrix properties. This (mechano)reciprocity between cells and the extracellular matrix (ECM) is central in regulating tissue functions and it is fundamentally important to broadly consider the biomechanical properties of the in vivo ECM when designing in vitro matrix models. This manuscript discusses two commonly used biopolymer networks, i.e. collagen and fibrin gels, and one synthetic polymer network, polyisocyanide gel (PIC), which all possess the characteristic nonlinear mechanics in the biological stress regime. We start from the structure of the materials, then address the uses, advantages, and limitations of each material, to provide a guideline for tissue engineers and biophysicists in utilizing current materials and also designing new materials for 3D cell culture purposes.

Apple ring rot, one of the most common apple postharvest diseases during storage, is caused by Botryosphaeria dothidea. Fungicide application is the most widely used method to control this disease, but the increasing environmental and food safety concerns greatly limit their use. The present study aimed to examine the biocontrol activity and underlying action mechanism of Bacillus halotolerans strain Pl7 against B. dothidea. The results revealed that B. halotolerans strain Pl7 exhibited strong inhibitory activity against B. dothidea by 69% in vitro. The culture filtrate of strain Pl7 possessed cellulase, β-1, 3-glucanase, protease activity and mediated the antifungal activity against B. dothidea. Further analysis demonstrated that culture filtrate of strain Pl7 could cause cell membrane permeabilization of B. dothidea. Apple fruit suffering from ring rot induced by a carbendazim (CBZ)-sensitive or -resistant B. dothidea isolate was much suppressed after being treated with strain Pl7, maintaining postharvest quality. The ability of strain Pl7 to swiftly colonize and thrive in apple fruit wounds was demonstrated by a re-isolation assay. Additional transcriptome studies of untreated and treated apple fruit with strain Pl7 revealed that strain Pl7 mostly changed the expression of genes functioning in plant secondary metabolite biosynthesis and plant-pathogen interaction. In light of these outcomes, the underlying antagonistic mechanism was investigated, and B. halotolerans strain Pl7 was identified as a promsing microbial biocontrol agent against apple postharvest decay.

Abstract Background Acute kidney injury (AKI) is a frequent complication of community acquired pneumonia (CAP). However, the impact of AKI on in-hospital outcomes of patients with CAP in the Chinese population remains unclear. Methods Patients diagnosed with CAP were evaluated in this retrospective observational study. Multiple Cox regression models were employed to identify the association between AKI and in-hospital mortality and 30-day mortality, respectively. Results A total of 4213 patients were recruited; 950 (22.5%) patients were diagnosed with AKI. Independent risk factors for AKI were age, male gender, hypertension, cardiac dysfunction, diabetes, chronic kidney disease, acute respiratory failure, use of diuretics, use of vasoactive drugs, and CURB-65. Cox proportional hazards regression revealed AKI, use of angiotensin receptor blocker, hypertension, CURB-65, acute respiratory failure, and use of vasoactive drugs to be independent risk factors for both in-hospital and 30-day mortality. Compared to patients without AKI, those suffering AKI were found to have 1.31-fold (HR 1.31, 95% CI, 1.04–1.66; P = 0.023) and 1.29-fold (HR 1.29, 95% CI, 1.02–1.62; P = 0.033) increased in-hospital and 30-day mortality risks, respectively. In addition, patients with AKI were likely to require admission to intensive care unit (ICU) (42.9% versus 11.4%; P

Abstract The powdery mildew fungi secrete numerous Candidate Secreted Effector Proteins (CSEPs) to manipulate host immunity during infection of host plants. However, the function of most of these CSEPs in cell death suppression has not yet been established. Here, we identified several CSEPs from Blumeria graminis f. sp. hordei (Bgh) that have the potential to suppress BAX- and NtMEK2DD-triggered cell death in Nicotiana benthamiana. We further characterized two effector candidates, CSEP0139 and CSEP0182, from family six and thirty-two, respectively. CSEP0139 and CSEP0182 contain a functional signal peptide and are likely secreted effectors. Expression of either CSEP0139 or CSEP0182 suppressed cell death triggered by BAX and NtMEK2DD but not by the AVRa13/MLA13 pair in N. benthamiana. Transient overexpression of CSEP0139 or CSEP0182 also inhibited BAX-induced cell death and collapse of cytoplasm in barley cells. Furthermore, overexpression of either CSEPs significantly increased Bgh haustorial formation in barley, whereas host-induced gene silencing (HIGS) of the CSEP genes reduced haustorial formation, suggesting both CSEPs promote Bgh virulence in barley. In addition, expression of CSEP0139 and CSEP0182 reduced size of the lesions caused by the necrotrophic Botrytis cinerea in N. benthamiana. Our findings suggest that CSEP0139 and CSEP0182 may target cell death components in plants to promote fungal virulence, which extends the current understanding of the functions of Bgh CSEPs and provides an opportunity for further investigation of fungal virulence in relation to cell death pathways in host plants.

Pear Valsa canker caused by Valsa pyri is among the most destructive diseases of pear, which causes significant economic loss. The present study was developed to explore the biocontrol efficiency and underlying antagonistic mechanism of Paenibacillus polymyxa strain Nl4 against V. pyri. P. polymyxa strain Nl4, one of the 120 different endophytic bacterial strains from pear branches, exhibited strong inhibitory effects against the mycelial growth of V. pyri and caused hyphal malformation. Culture filtrate derived from strain Nl4 was able to effectively suppress mycelial growth of V. pyri, and was found to exhibit strong protease, cellulase and β-1, 3-glucanase activity. Through re-isolation assay, strain Nl4 was confirmed to be capable of colonizing and surviving in pear branch. Treatment with strain NI4 effectively protected against pear Valsa canker symptoms on detached pear twigs inoculated with V. pyri. Moreover, strain Nl4 promoted enhanced plant growth probably through the solubilization of phosphorus. Comparative transcriptomic analyses revealed that strain NI4 was able to suppress V. pyri growth in large part through the regulation of the expression of membrane- and energy metabolism-related genes in this pathogen. Further transcriptomic analyses of pear trees indicated that strain NI4 inoculation was associated with changes in the expression of genes associated with secondary metabolite biosynthesis, signal transduction, and cutin, suberine, and wax biosynthesis. Together, these data highlighted P. polymyxa strain Nl4 as a promising biocontrol agent against pear Valsa canker and investigated the possible mechanisms of strain Nl4 on control of this devastating disease.

Triticum urartu, a diploid wild wheat and progenitor of the A genome of bread wheat, is an important resource for resistance to powdery mildew fungus caused by Blumeria graminis f. sp. tritici (Bgt). In the present study we systematically characterized the interaction between the Bgt fungus and T. urartu at the microscopic level. We also tested 227 T. urartu accessions for reaction to Bgt isolate E09 and discovered previously uncategorized powdery mildew resistance in this collection. Pm60 is a CC-NB-LRR type powdery mildew resistance gene that has at least three functional alleles, Pm60, Pm60a, and Pm60b. A marker-assisted screen targeting the Pm60 locus identified a non-functional allele of Pm60a, designated as Pm60a′. A sequence comparison of Pm60a′ and Pm60a revealed that they differed by 58 SNPs and one 3-nucleotide deletion. Based on the sequence variations two molecular markers were developed to differentiate the functional Pm60a allele from the non-functional Pm60a′. Our screen revealed the presence of a previously uncharacterized powdery mildew resistance in T. urartu and provides new insights into the Pm60 locus. We believe that the two molecular markers developed here and new T. urartu resistant accessions will facilitate further identification of novel powdery mildew resistance genes and benefit breeding for powdery mildew resistance. Keywords: Blumeria graminis, Diploid wheat, Molecular marker, Pm60 alleles

The common method for evaluating the extent of grape disease is to classify the disease spots according to the area. The prerequisite for this operation is to accurately segment the disease spots. This paper presents an improved DeepLab v3+ deep learning network for the segmentation of grapevine leaf black rot spots. The ResNet101 network is used as the backbone network of DeepLab v3+, and a channel attention module is inserted into the residual module. Moreover, a feature fusion branch based on a feature pyramid network is added to the DeepLab v3+ encoder, which fuses feature maps of different levels. Test set TS1 from Plant Village and test set TS2 from an orchard field were used for testing to verify the segmentation performance of the method. In the test set TS1, the improved DeepLab v3+ had 0.848, 0.881, and 0.918 on the mean intersection over union (mIOU), recall, and F1-score evaluation indicators, respectively, which was 3.0, 2.3, and 1.7% greater than the original DeepLab v3+. In the test set TS2, the improved DeepLab v3+ improved the evaluation indicators mIOU, recall, and F1-score by 3.3, 2.5, and 1.9%, respectively. The test results show that the improved DeepLab v3+ has better segmentation performance. It is more suitable for the segmentation of grape leaf black rot spots and can be used as an effective tool for grape disease grade assessment.

Background: Ticagrelor belongs to a new class of P2Y12 receptor inhibitor that has been widely used for antiplatelet therapy. This study aimed to explore the effect of single nucleotide polymorphisms (SNPs) in metabolic enzymes, transporters, and other relevant variants on the pharmacokinetics (PK) of ticagrelor and its active metabolite, AR-C124910XX.Methods: The study population comprised 68 healthy Chinese volunteers who were enrolled in a ticagrelor bioequivalence clinical trial. The PK profile of ticagrelor was evaluated after orally administering a single 90-mg dose of ticagrelor in tablet form. The plasma concentrations of ticagrelor and AR-C124910XX were determined through liquid chromatography–tandem mass spectrometry. Plasma DNA samples were used to explore the effect of gene polymorphisms on the PK of ticagrelor and AR-C124910XX with whole-exome sequencing.Results: Female participants had a higher maximum plasma concentration/weight ratio (Cmax/W; p

Botryosphaeria dothidea causes apple ring rot, which is among the most prevalent postharvest diseases of apples and causes significant economic loss during storage. In this study, we investigated the biocontrol activity and possible mechanism of Bacillus velezensis strain P2-1 isolated from apple branches against B. dothidea in postharvest apple fruit. The results showed strain P2-1, one of the 80 different endophytic bacterial strains from apple branches, exhibited strong inhibitory effects against B. dothidea growth and resulted in hyphal deformity. B. velezensis P2-1 treatment significantly reduced the ring rot caused by B. dothidea. Additionally, the supernatant of strain P2-1 exhibited antifungal activity against B. dothidea. Re-isolation assay indicated the capability of strain P2-1 to colonize and survive in apple fruit. PCR and qRT-PCR assays revealed that strain P2-1 harbored the gene clusters required for biosynthesis of antifungal lipopeptides and polyketides. Strain P2-1 treatment significantly enhanced the expression levels of pathogenesis-related genes (MdPR1 and MdPR5) but did not significantly affect apple fruit qualities (measured in fruit firmness, titratable acid, ascorbic acid, and soluble sugar). Thus, our results suggest that B. velezensis strain P2-1 is a biocontrol agent against B. dothidea-induced apple postharvest decay. It acts partially by inhibiting mycelial growth of B. dothidea, secreting antifungal substances, and inducing apple defense responses.

Powdery mildew is one of the most important fungal pathogen diseases. The genome of barley mildew fungus, Blumeria graminis f. sp. hordei (Bgh), encodes a large number of candidate secreted effector proteins (CSEPs). So far, the function and mechanism of most CSEPs remain largely unknown. Here, we identify a Bgh effector CSEP0027, a member of family 41, triggering cell death in Nicotiana benthamiana. CSEP0027 contains a functional signal peptide (SP), verified by yeast secretion assay. We show that CSEP0027 promotes Bgh virulence in barley infection using transient gene expression and host-induced gene silencing (HIGS). Barley catalase HvCAT1 is identified as a CSEP0027 interactor by yeast two-hybrid (Y2H) screening, and the interaction is verified in yeast, in vitro and in vivo. The coexpression of CSEP0027 and HvCAT1 in barley cells results in altered localization of HvCAT1 from the peroxisome to the nucleus. Barley stripe mosaic virus (BSMV)-silencing and transiently-induced gene silencing (TIGS) assays reveal that HvCAT1 is required for barley immunity against Bgh. We propose that CSEP0027 interacts with barley HvCAT1 to regulate the host immunity and likely reactive oxygen species (ROS) homeostasis to promote fungal virulence during barley infection.

The disease spots on the grape leaves can be detected by using the image processing and deep learning methods. However, the accuracy and efficiency of the detection are still the challenges. The convolutional substrate information is fuzzy, and the detection results are not satisfactory if the disease spot is relatively small. In particular, the detection will be difficult if the number of pixels of the spot is

Objective To determine whether assessment tools for non-randomised studies (NRS) address critical elements that influence the validity of NRS findings for comparative safety and effectiveness of medications.Design Systematic review and Delphi survey.Data sources We searched PubMed, Embase, Google, bibliographies of reviews and websites of influential organisations from inception to November 2019. In parallel, we conducted a Delphi survey among the International Society for Pharmacoepidemiology Comparative Effectiveness Research Special Interest Group to identify key methodological challenges for NRS of medications. We created a framework consisting of the reported methodological challenges to evaluate the selected NRS tools.Study selection Checklists or scales assessing NRS.Data extraction Two reviewers extracted general information and content data related to the prespecified framework.Results Of 44 tools reviewed, 48% (n=21) assess multiple NRS designs, while other tools specifically addressed case–control (n=12, 27%) or cohort studies (n=11, 25%) only. Response rate to the Delphi survey was 73% (35 out of 48 content experts), and a consensus was reached in only two rounds. Most tools evaluated methods for selecting study participants (n=43, 98%), although only one addressed selection bias due to depletion of susceptibles (2%). Many tools addressed the measurement of exposure and outcome (n=40, 91%), and measurement and control for confounders (n=40, 91%). Most tools have at least one item/question on design-specific sources of bias (n=40, 91%), but only a few investigate reverse causation (n=8, 18%), detection bias (n=4, 9%), time-related bias (n=3, 7%), lack of new-user design (n=2, 5%) or active comparator design (n=0). Few tools address the appropriateness of statistical analyses (n=15, 34%), methods for assessing internal (n=15, 34%) or external validity (n=11, 25%) and statistical uncertainty in the findings (n=21, 48%). None of the reviewed tools investigated all the methodological domains and subdomains.Conclusions The acknowledgement of major design-specific sources of bias (eg, lack of new-user design, lack of active comparator design, time-related bias, depletion of susceptibles, reverse causation) and statistical assessment of internal and external validity is currently not sufficiently addressed in most of the existing tools. These critical elements should be integrated to systematically investigate the validity of NRS on comparative safety and effectiveness of medications.Systematic review protocol and registration https://osf.io/es65q.

Plant architecture characteristics contribute significantly to the microclimate within peanut canopies, affecting weed suppression as well as incidence and severity of foliar and soil-borne diseases. However, plant canopy architecture is difficult to measure and describe quantitatively. In this study, a ground-based LiDAR sensor was used to scan rows of peanut plants in the field, and a data processing and analysis algorithm was developed to extract feature indices to describe the peanut canopy architecture. A data acquisition platform was constructed to carry the ground-based LiDAR and an RGB camera during field tests. An experimental field was established with three peanut cultivars at Oklahoma State University's Caddo Research Station in Fort Cobb, OK in May and the data collections were conducted once each month from July to September 2015. The ground-based LiDAR used for this research was a line-scan laser scanner with a scan-angle of 100°, an angle resolution of 0.25°, and a scanning speed of 53 ms. The collected line-scanned data were processed using the developed image processing algorithm. The canopy height, width, and shape/density were evaluated. Euler number, entropy, cluster count, and mean number of connected objects were extracted from the image and used to describe the shape of the peanut canopies. The three peanut cultivars were then classified using the shape features and indices. A high correlation was also observed between the LiDAR and ground-truth measurements for plant height. This approach should be useful for phenotyping peanut germplasm for canopy architecture.

Valsa canker caused by Valsa pyri is one of the most destructive diseases of commercial pear. For the present analysis, 29 different endophytic fungal strains were isolated from the branches of a healthy pear tree. In dual culture assays, strain ZZ1 exhibited robust antifungal activity against all tested pathogens including Valsa pyri. Microscopic analyses suggested that following co-culture with ZZ1, the hyphae of V. pyri were ragged, thin, and ruptured. ZZ1 also induced significant decreases in lesion length and disease incidence on detached pear branches inoculated with V. pyri. ZZ1 isolate-derived culture filtrates also exhibited antifungal activity against V. pyri, decreasing mycelial growth and conidium germination and inhibiting V. pyri-associated lesion development on pear branches. These results suggest that the ZZ1 isolate has the potential for use as a biological control agent against V. pyri. The strain was further identified as Penicillium citrinum based on its morphological characteristics and molecular analyses. Overall, these data highlight a potentially valuable new biocontrol resource for combating pear Valsa canker.

Kiwifruit is very popular among consumers due to its high nutritional value. The increasing expansion in kiwifruit cultivation has led to the spread of rot diseases. To identify the pathogens causing kiwifruit ripe rots in China, 24 isolates were isolated from the diseased fruit and wart in trees. Botryosphaeria dothidea was recognized as the pathogen causing kiwifruit ripe rot and wart in the tree through internal transcribed spacer (ITS) sequencing, pathogenicity testing, morphological and microscopic characteristics. The rapid and accurate detection of this pathogen will lead to better disease monitoring and control efforts. A loop-mediated isothermal amplification (LAMP) method was then developed to rapidly and specifically identify B. dothidea. These results offer value to further research into kiwifruit ripe rot, such as disease prediction, pathogen rapid detection, and effective disease control.

Ethnopharmacological relevance: Pelvic inflammatory disease (PID) is a frequently occurring gynecological disorder mainly caused by the inflammation of a woman's upper genital tract. Generally, antibiotics are used for treating PID, but prolonged use poses potential risks of gut bacterial imbalance, bacterial resistance, super bacteria production, and associated adverse reactions. Traditional Chinese medicine (TCM) has shown unique advantages in various ailments and has received widespread clinical research attention. Fuke Qianjin (FUKE) capsule is an approved National Medical Products Administration (NMPA License No. Z20020024) Chinese herbal prescription that has been widely used individually or in combination with other Western medicines for the treatment of various gynecological inflammatory diseases, including chronic cervicitis, endometritis, and chronic PID. Aim: This clinical trial was designed to assess the safety and efficacy of FUKE capsule in mild-to-moderate symptomatic PID patients. Materials and methods: This phase 2, randomized, double-blind, positive controlled clinical trial was conducted in mild-to-moderate symptomatic PID patients at a single center in Pakistan from 21 September 2021 to 11 March 2022. Eligible female participants were randomly assigned to a test and a control group with a ratio of 1:1. The test group subjects received two metronidazole (METRO) tablets and one doxycycline hyclate (DOXY) simulant at a time, twice daily for 14 days, and two Fuke Qianjin (FUKE) capsules, three times a day after a meal for 28 days. Subjects in the control group received two METRO tablets and one DOXY tablet at a time, twice daily for 14 days, and two FUKE simulant capsules, three times a day after meal for 28 days. The primary efficacy outcome was an improvement in pelvic pain symptoms assessed through a visual analog scale (VAS). The secondary outcomes were the improvement in secondary efficacy symptoms like local physical signs, clinical assessment of leucorrhea and cervical secretions through laboratory examination, and improvement in the maximum area of pelvic effusion assessed through gynecological ultrasound after the treatment. The safety outcomes were assessed through vital signs, laboratory tests, electrocardiogram findings, and adverse events/serious adverse events. Results: A total of 198 subjects with active PID were randomly assigned to a test group (n = 99) and a control group (n = 99). The baseline characteristics of the subjects in the two groups were similar. In the intention-to-treat analysis, the primary efficacy was 84.9% for the test group and 71.6% for the control group, with a statistically significant difference (p = 0.0370; 95% CI -0.2568 to -0.0088). The secondary clinical efficacy was 88.4% for the test group and 82.7% for the control group, with no significant difference (p = 0.2977; 95% CI -0.1632 to 0.0501). The improvement in local physical signs was 95.8% for the test group and 76.9% for the control group, with no significant difference (p = 0.0542; 95% CI -0.3697 to -0.0085). The inter-group non-inferiority comparison showed that the upper limit of the 95% CI was less than 0.15 and thus met the noninferiority requirements of the test group to the control group. The results of clinical signs of leucorrhea and cervical secretions showed that there was no difference in the rate of improvement between the test and control groups, indicating that FUKE was non-inferior to DOXY. A total of 14 adverse events in eight subjects were observed in the trial, with an incidence rate of 4.7%. Four subjects in each group experienced seven adverse events with 4.5% and 4.8% incidence rates of adverse reactions in the test and control groups, with no statistically significant differences (p = 0.2001). No serious adverse events occurred in the trial. Conclusion: The results of this trial indicate that the test drug (Fuke Qianjin capsule) is non-inferior to the control drug (doxycycline hyclate tablet) in treating mild-tomoderate PID patients with comparable efficacy, safety, and tolerability to the control drug. [ABSTRACT FROM AUTHOR]

Cells continuously sense external forces from their microenvironment, the extracellular matrix (ECM). In turn, they generate contractile forces, which stiffen and remodel this matrix. Although this bidirectional mechanical exchange is crucial for many cell functions, it remains poorly understood. Key challenges are that the majority of available matrices for such studies, either natural or synthetic, are difficult to control or lack biological relevance. Here, we use a synthetic, yet highly biomimetic hydrogel based on polyisocyanide (PIC) polymers to investigate the effects of the fibrous architecture and the nonlinear mechanics on cell-matrix interactions. Live-cell rheology was combined with advanced microscopy-based approaches to understand the mechanisms behind cell-induced matrix stiffening and plastic remodeling. We demonstrate how cell-mediated fiber remodeling and the propagation of fiber displacements are modulated by adjusting the biological and mechanical properties of this material. Moreover, we validate the biological relevance of our results by demonstrating that cellular tractions in PIC gels develop analogously to those in the natural ECM. This study highlights the potential of PIC gels to disentangle complex bidirectional cell-matrix interactions and to improve the design of materials for mechanobiology studies. [ABSTRACT FROM AUTHOR]