bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical outcomes of fetal ovarian masses diagnosed by prenatal ultrasonography and literature review
Authors: Min Jie , Tang Ruze , Zhi Wenxian , Gu Zhicheng , Huang Shungen , Wang Jian
Published: October 2022

With the advancement of prenatal examination technology, more and more fetus with ovarian masses are diagnosed. However, whether such children need intervention measures after delivery, there is no more unified diagnosis and treatment measures in the world. In this study, postnatal data and clinical outcome of fetal diagnosed with ovarian masses were analyzed. We also combined with relevant literature to explore the postpartum intervention measures and timing of such children. A total of 57 cases of abdominal masses from the reproductive system were included in the study. These children were diagnosed with ovarian masses after birth. We collected from 2012 to 2020, the prenatal examination revealed the presence of abdominal masses from the reproductive system, and diagnosis was confirmed by imaging examinations after childbirth. We counted the fetal period data of these children, compared the changes in the postnatal pathology and intervention measures. A total of 57 cases of ovarian masses were diagnosed prenatally, 1 case was lost to follow-up, and 56 cases were finally included in the study. After birth a total of 21 cases of ovarian masses were treated conservatively, of which 18 cases resolved spontaneously during the follow-up process, with an average follow-up period of 30.88 ± 18.16 weeks. There were statistically significant differences in the nature and the maximum diameter of the mass between the two groups receiving conservative treatment or surgical treatment after delivery (P < .05).Univariate and multivariate Logistic regression analysis showed that there were significant differences in the nature and diameter of the mass between two groups (P < .05). In addition, we divided the children undergoing postpartum surgery into a laparoscopic surgery group and a conventional open surgery group. Through data analysis, we found that there were statistically significant differences in the age of operation, operation time, and hospitalization days in the two groups of these children (P < .05). Children diagnosed with ovarian masses prenatally generally have a good prognosis. For these children, the treatment plan should be developed according to the child general condition. If child with ovarian mass is treated with surgery, the preservation of ovarian tissue should be emphasized regardless of the size, nature, and torsion of the mass.
Evaluation of the effect of pharmaceutical care during inpatient treatment in a department of neurology: A retrospective study
Authors: Ji Wen , Xiao Ruowei , Wu Bei , Han Sheng , Duan Jinju , Meng Zhiqiang , Yang Mingxu , Wang Chen
Published: October 2022

Common drug-related problems during neurology inpatient treatment can affect expected health results. Some interventions need to be implemented to reduce DRPs. To explore the effect of care from clinical pharmacists during inpatient treatment. Inpatients treated in the department of neurology in the Second Hospital of Shanxi Medical University between January 1 to December 31, 2019, were retrospectively included. Those who received care from the clinical pharmacist service were assigned to the pharma-care group while the other patients were assigned to the control group. From the perspective of drugs, the two groups were compared in terms of types, antimicrobial use, and key monitoring of drug use. From the perspective of patients, the two groups were compared in terms of length of stay, hospital cost, drug cost and proportion. Propensity score matching was used to balance the baseline characteristics. A total of 2684 patients were included 554 in the pharma-care group and 2130 in the control group with a median of 9 days (range, 3–30 days) hospital stay. The groups showed no significant difference in age or gender. Length of stay, the proportion of drug cost, number of adverse events, cost of antibacterial agents, use of a single antibacterial agent, and use of three or more different antibacterial agents were similar between the groups. Medicine expenses cost more in the pharma-care group. The cost and types of intensive monitoring drugs were similar, but Defined Daily Doses were lower in the control group. While clinical pharmacists may play a positive role in the pharmaceutical care of inpatients, in this study the benefits were not obvious. This may be because of the small number of clinical pharmacists in the department of neurology with narrow coverage.
Safflor yellow treating angina pectoris: A pharmacoeconomic evaluation and network meta-analysis
Authors: Lu Liang , Li Yang , Jin Qiuchen , Chen Yongfa
Published: October 2022

Background:

Coronary heart disease (CHD) is a cardiovascular disease caused by myocardial ischemia. In China, safflor yellow and artemisinin-based combination therapies have been extensively used to treat angina pectoris.

Methods:

Efficacies were provided by a network meta-analysis following the PRISMA 2020 checklist. Cost-effectiveness analysis was based on patient perspectives. Two-way and probabilistic sensitivity analyses were conducted to assess the robustness of the study results.

Results:

Conventional treatment combined with safflower is a better choice against angina pectoris. Sensitivity analysis showed that the model was sensitive to the treatment efficacy rather than the drug cost.

Conclusion:

Conventional treatment combined with safflower injection is suggested to treat angina pectoris. Low molecular weight heparin or compound Danshen-dropping pills can be used to increase the recovery rate of angina pectoris, according to conventional treatment combined with safflower injection.
Evaluations of aqueous humor protein markers in different types of glaucoma
Authors: Chen Haiyan , Zheng Gang , Chen Huijie , Li Lu , Xu Zhuojun , Xu Li
Published: October 2022

To compare the concentrations of protein markers in aqueous humor (AH) of patients with primary open-angle glaucoma (POAG), chronic angle-closure glaucoma (CACG), acute primary angle closure (APAC), and cataract without glaucoma as the control group.

AH samples were collected at the beginning of surgery from 82 eyes of 82 patients who were divided into POAG (n = 23), CACG (n = 21), APAC (n = 19), and cataract groups (n = 19). The expression levels of interferon-gamma (IFN-γ), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-17A (IL-17A), lymphotoxin-alpha (LT-α), monocyte chemotactic protein-1 (MCP-1), matrix metalloproteinase-2 (MMP-2), brain derived neurotrophic factor (BDNF), basic fibroblast growth factor (bFGF), platelet-derived growth factor-AA (PDGF-AA), vascular endothelial growth factor (VEGF), tissue inhibitor of metalloproteinases-1 (TIMP-1), and tumor necrosis factor-alpha (TNF-α) in AH were detected using a microsphere-based immunoassay.

The AH levels of TNF-α, MMP-2, MCP-1, IFN-γ, and TIMP-1 in the APAC and CACG groups were significantly higher than those in control eyes. Additionally, the AH levels of interleukin-6 (IL-6) and VEGF in the APAC group were significantly higher than those in the control group (CG). The interleukin-8 (IL-8) levels in patients with POAG were significantly higher than those in control eyes, whereas the LT-α levels were significantly lower than those in control eyes. IL-6 levels were significantly correlated with the coefficient of variation (CV), whereas IL-6 levels were significantly negatively correlated with the frequency of hexagonal cells (HEX) and corneal endothelial cell density (CD).

The levels of TNF-α, MMP-2, MCP-1, IFN-γ, TIMP-1, IL-6, IL-8, VEGF, and LT-α were different among the three types of glaucoma. These different types of glaucoma may be caused by various pathogeneses, which opens avenues for further investigation into the pathogenesis of glaucoma and discoveries new targets and pathways for the treatment of glaucoma.
Construction of a transcription factor-miRNA-mRNA interactive network elucidates underlying pathogenesis for osteosarcoma and validation by qRT-PCR
Authors: Tang Fuxing , Jiang Xiaohong , Liao Shijie , Liu Yun , He Maolin
Published: October 2022

Purpose:

Osteosarcoma is characterized by features of rapid growth and early metastasis with a poor prognosis. The aim of our research is to investigate the potential transcription factor (TF)-miRNA-mRNA regulatory mechanism in osteosarcoma utilizing bioinformatics methods and validate by qRT-PCR.

Methods:

The microRNA (miRNA) expression profiling datasets (GSE28423 and GSE65071) and mRNA expression profiling dataset GSE33382 were collected from the Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) were screened using the limma package. Then, the TransmiR v2.0, miRDB, and Targetscan 7.2 database were applied for the acquisition of TF-miRNA and miRNA-mRNA interaction relationships, respectively. Finally, we built a TF-miRNA-mRNA interactive network. Furthermore, survival analysis was performed to identify sub-network with prognostic value and validate through qRT-PCR.

Results:

Eight overlapping DEMs and 682 DEGs were identified. Based on bioinformatics methods, 30 TF-miRNA interaction pairs and 25 miRNA-mRNA interaction pairs were screened. Finally, we constructed a TF-miRNA-mRNA regulatory network. Furthermore, laminin subunit gamma 1 (LAMC1) and thrombospondin-1 (THBS1), which involved in the network, were determined to have prognostic value and the corresponding subnetwork was identified. qRT-PCR results showed that LAMC1 mRNA expression was higher in osteosarcoma cells.

Conclusion:

Based on the survival analysis, a TF-miRNA–mRNA sub-network, that is TFs (SPI1, HEY1, and CEBPB)-hsa-miR-338-3p-target genes (LAMC1 and THBS1) was established. In conclusion, the construction of a potential TF-related regulatory network will help elucidate the underlying pathological mechanisms of osteosarcoma, and may provide novel insights for the diagnosis and treatment of osteosarcoma.
Risk factors for in-hospital systemic thromboembolism in myocardial infarction patients with left-ventricular thrombus: A multicenter retrospective study
Authors: Zhou Wei , Shi Shun-Yi , Ye Fei , Ji Yuan , Huang Jun , Yang Song , Yang Lin , Huang Shenglan
Published: October 2022

Left-ventricular thrombus (LVT) is a potentially life-threatening disease. However, few studies have explored the risk factors of in-hospital systemic thromboembolism (ST) in LVT patients. In this multicenter retrospective study, we enrolled myocardial infarction patients with LVT from January 2008 to September 2021. Multivariable logistic regression analysis was applied to identify the independent risk factors for ST in LVT patients. A total number of 160 hospitalized LVT patients [median follow-up period 50 months (18.3–82.5 months)] were subjected to analysis. Of them, 54 (33.8%) patients developed acute myocardial infarction, 16 (10%) had ST, and 33 (20.6%) died. Comparable baseline characteristics were established between the ST and non-ST groups, except for the heart failure classification (P = .014). We obtained the following results from our multivariable analysis, based on the use of HFrEF as a reference: HFpEF [odd ratio (OR), 6.2; 95% confidence interval (CI), 1.4–26.3; P = .014] and HFmrEF (OR, 5.0; 95%CI, 1.1–22.2; P = .033). In conclusion, HFpEF, and HFmrEF may be independent risk factors for in-hospital ST development.
Vision loss due to uncommon “red eye”: A case report
Authors: Xu-yuan Tang , Rui-nan Qi , Ze-yong Wu , Juan Li , Tao Xie , Yi-qun Yuan
Published: October 2022

Rationale:

Phacolytic glaucoma is a rare complication induced by hypermature cataracts and may occasionally be encountered in some rural areas. It tends to be misdiagnosed and induces a risk of permanent vision impairment.

Patient concerns:

A 63-year-old Uighur woman complained of redness and decreased vision in her right eye and was treated for endophthalmitis at a primary hospital before being referred to our hospital.

Diagnosis:

On admission, the patient had weak light perception in the right eye, an intraocular pressure of 65 mmHg, and slit-lamp examination revealed swelling of the eyelids and significant injection of conjunctiva. The entire cornea was cloudy and edematous, whereas the aqueous humor was milky turbid. Cytological examination of the aqueous liquid confirmed the presence of lens protein-laden macrophages. A Morgagnian cataract was observed after anterior chamber irrigation. So the final diagnosis was phacolytic glaucoma.

Interventions:

The patient received anterior chamber irrigation and extracapsular cataract extraction with intraocular lens implantation successively.

Outcomes:

Final visual acuity was limited to 6/120 due to secondary optic nerve damage.

Lessons:

Phacolytic glaucoma can mimic endophthalmitis and tend to be misdiagnosed, causing permanent vision impairment. Improving awareness of phacolytic glaucoma and enhancing public health education regarding cataracts are ways to prevent phacolytic glaucoma and phacolytic glaucoma-related vision loss.
Clinical significance of asymmetric venous vasculature on minimum-intensity projection in patients with moyamoya disease
Authors: Han Min Jeong , Kim Sun Jun
Published: October 2022

This study analyzed the clinical significance and characteristics of asymmetric venous blood flow in patients with Moyamoya disease (MMD) using minimum intensity projection (minIP) susceptibility-weighted imaging. The minIP views of 30 patients diagnosed with MMD were retrospectively analyzed using clinical features, brain magnetic resonance angiography, electroencephalography, and brain single-photon emission computed tomography (SPECT). Simultaneously, differences between patients with acute cerebral infarction and non-MMD causes were analyzed. Twelve (40.0%) of the 30 patients had asymmetrical venous flow, which is usually seen in patients with acute cerebral infarction (P = .146). They also had significantly higher Suzuki stages than symmetric patients (P = .014), with five (41.7%) and three (25.0%) of them in stages 4 and 5, respectively. When the Suzuki stages of both hemispheres were different, more veins were found in the stenotic hemisphere (88.9%). Brain SPECT showed more severe hypoperfusion on the side with prominent vascularity in the minIP view (100.0%). Additionally, asymmetric blood flow was observed in 66.7% of the patients with cerebral infarction caused by MMD, whereas only 11.1% of the children with cerebral infarction caused by non-MMD had asymmetry (P = .005). Patients with MMD showed asymmetric hypointensity of the cortical veins with a minIP appearance. The venous structure showed greater signal loss on SWI and was more prominent in the hemisphere where stenosis was advanced or infarction occurred in other examinations. Cerebral infarction in patients with MMD tended to occur with asymmetrically prominent venous patterns with damaged areas in minIP images, which had distinct characteristics from those of patients without MMD.
Puerperium could have better intensive care outcomes with acute respiratory distress syndrome caused by COVID-19
Authors: Tulubas Evrim Kucur , Çetingök Halil
Published: October 2022

Acute respiratory distress syndrome (ARDS) with (COVID-19 often result in mortality. Treatment outcomes among puerperant, when compared with non-pregnant women (NPW) with the same syndrome. Physiological changes underwent within the gestation period have a considerable impact on the immune system, respiratory system, cardiovascular function, and coagulation. Through this research, it was aimed to compare intensive care unit (ICU) follow-up and treatment results of postpartum-period patients with those of non-pregnant ones. During the first week of ICU, 23 puerperant COVID-19 patients with ARDS and 34 non-pregnant COVID-19 patients took part in the study. Age, height, and predictive body weight (PBW) at admission to the ICU were compared with the clinical parameters of disease severity, such as FiO2 (fraction of inspired oxygen), PaO2 (arterial oxygen partial pressure), Horowitz index (PaO2/FiO2), procalcitonin (PCT), and C-reactive protein (CRP). Respiration parameters were recorded a meta-vision back server. Demographic data, FiO2, PaO2, Horowitz index, PCT, CRP and respiration parameters values were similar in both groups. The duration of non-mechanical ventilation and number of patients were seen to be significantly greater among the puerperant group than control group (P; .04 and .002, respectively). The duration of mechanical ventilation was similar in both groups (P; .07), while the mortality rate was lower in the puerperant group (P; .004). The postpartum women with COVID-19 induced ARDS were observed to have better ICU follow-up results and lower mortality. However, it is considered that the present results need to be supported greater number of participants.
Aerobic exercises and cognitive function in post-stroke patients: A systematic review with meta-analysis
Authors: Li Xiaogang , Geng Di , Wang Siyue , Sun Guotao
Published: October 2022

Objective:

To study the effect of aerobic exercise on cognitive function of post-stroke patients, especially to identify specific interventions that the most likely to maximize cognitive benefits of stroke patients.

Methods:

According to the PRISMA principle, the databases of Web of Science, EMBASE, PubMed and Cochrane library were searched to collect randomized controlled trial data of aerobic exercise on cognitive function intervention of post-stroke patients. The Cochrane bias risk evaluation instrument was used to assess the methodological quality of included studies. Review Manager 5.4.1 software was used to analyze heterogeneity and potential publication bias.

Results:

A total of 11 criteria studies that satisfied the association between aerobic exercise and cognitive function following stroke were selected to be included in the review. Global cognition ability was significantly improved after aerobic exercise intervention (0.51; 95% confidence interval [CI] 0.16–0.86; P = .004), moderate intensity had the largest effect size on improving global cognition ability (0.98; 95% CI 0.48–1.47; P = .0001), none of cognitive flexibility, working memory, selective attention and conflict resolution showed the significant difference from zero.

Conclusion:

Aerobic exercise has a good impact on enhancing the cognitive dysfunction of patients after stroke, which stroke patients were found to benefit the most from moderate-intensity exercise. However, our studies did not found that aerobic exercise had an active result on cognitive flexibility, working memory, selective attention and contention resolution.
Clinical study on the treatment of male infertility with Wuwei Fuzheng Yijing decoction based on microplastics: Study protocol for a randomized controlled trial
Authors: Ma Miaomiao , Ju Baojun , Li Xiao , Yao Junchao , Li Luyu , Zhang Yongtao , Tang Shuotong , Zhang Chenming
Published: October 2022

Background:

Environmental pollution and male infertility have become global public health problems. The presence of microplastics (MPs) has been detected in the human body, and it has also been demonstrated that MPs can cause damage to the reproductive system. Wuwei Fuzheng Yijing Decoction (WWFZYJ) is effective in treating male infertility. Therefore, we designed a clinical randomized controlled trial to observe the effect of WWFZYJ on the content of MPs and semen quality in male infertility patients, and to evaluate its security.

Methods:

In this randomized controlled study, 66 eligible patients were randomly assigned in a 1:1 ratio to a treatment group (WWFZYJ Decoction) and a control group (Coenzyme Q10 tablets combined with vitamin E soft capsules) for 8 weeks. The content of MPs in semen, sperm DNA Fragmentation Index (DFI), and semen analysis (including sperm density, sperm count, forward motile sperm, sperm motility, etc) will be used as primary indicators, and Traditional Chinese Medicine (TCM) syndrome scores will be used as secondary indicators. Vital signs (such as respiration, heart rate, body temperature, blood pressure, electrocardiogram, etc), blood routine, urine routine, stool routine, liver function, and renal function will be used as safety indicators. The primary and secondary indicators will be performed at 0th and 8th week, and the safety indicators will be performed at 0th, 4th, and 8th week.

Discussion:

This study will provide evidence for the efficacy and safety of WWFZYJ in treating male infertility and reducing the content of MPs in semen, and further explore the effects of MPs on male fertility.
Diagnostic evaluation for adrenal tumors – What does the urologist need to know about endocrine metabolic work up?
Authors: Garstka Nathalie , Remzi Mesut
Published: October 2022

Purpose of review

Adrenal lesions are commonly discovered on abdominal imaging studies, whereas some patients with adrenal tumors present with symptoms of homonal excess. They are categorized as either hormone active or inactive and either as benign or malignant. This review is focused on the endocrine work up in patients with adrenal tumors. Knowledge of the use and limitations of hormonal assessment is essential for propper interpretation of the obtained test results. This article reviews which diagnostics are necessary to identify adrenal masses requiring treatment.

Recent findings

Delayed hormonal assessment is not uncommon and associated with delayed treatment. The endocrine work up is guided by data from prospective and retrospective observational studies. Adrenal tumors include a wide spectrum of diseases and as a principle, most patients require biochemical testing to select the appropriate treatment.

The most important factor for the outcome in the management of adrenal masses is, beside the exclusion of malignancy, a structured evaluation of the patients endocrine status.
Standardizing Tobacco Cessation Counseling Using the 5 A's Intervention
Authors: Affentranger Ashley , Mulkey David
Published: October 2022

Background:

Tobacco use is the leading cause of preventable death due to cardiovascular disease.

Local problem:

Tobacco cessation counseling (TCC) is varied among providers, leading to suboptimal willingness to make a quit attempt.

Methods:

We used a quality improvement framework to pilot the 5 A's for TCC from April 2021 to August 2021 in our outpatient cardiology clinic.

Interventions:

Providers implemented TCC using the 5 A's intervention. Patient follow-up phone calls were conducted 30 days after receiving TCC.

Results:

Of 629 patient encounters, the mean TCC rate increased by 27.5%, and the mean reported cessation rates improved by 3.9%. Variation among providers decreased for TCC rates when they used the 5 A's intervention.

Conclusions:

The 5 A's intervention standardized TCC efforts. Using the 5 A's led to an increase in patients who reported smoking cessation 30 days after TCC was received.
Barriers to Implementing Weight Management Recommendations
Authors: Metcalf Kevin , Wright Lauri , Arikawa Andrea Y. , Ross Jenifer
Published: October 2022

Dietitians are responsible for using evidence-based practice to mitigate the effects of obesity; however, it is unclear how dietitians use research to guide weight management interventions. The aim of this pilot study was to identify the barriers of research utilization and implementation of evidence-based practice in adult weight management. A survey was disseminated to dietitians working at least part-time with people with obesity. Dietitians seem to value research and evidence-based practice; however, implementation may be an issue. The pilot study found that workplace setting may provide a barrier to research utilization, but dietitian opinion of current screening and referral guidelines may also be a significant barrier to implementing best practices in adult weight management.
Differential Detection of Hepatic Metastases on 68Ga-DOTATATE PET/CT and 177Lu-DOTATATE SPECT/CT
Authors: Zahed Hanan , Beauregard Jean-Mathieu , Abikhzer Gad , Rush Christopher , Probst Stephan
Published: October 2022

68Ga-DOTATATE PET/CT is indicated for selecting patients for peptide receptor radionuclide therapy (PRRT). Although highly sensitive, the detectability of smaller lesions, particularly in the liver, is lower. We present the case of a 58-year-old man with metastatic well-differentiated pancreatic neuroendocrine tumor whose MRI revealed progression of hepatic metastases. 68Ga-DOTATATE PET/CT performed to determine eligibility for PRRT did not demonstrate DOTATATE-avid disease within the liver. 18F-FDG PET/CT was also negative at the liver and the patient proceeded to 177Lu-DOTATATE PRRT, where multi–time point posttherapy planar imaging and SPECT/CT showed intense uptake in the known liver metastases.
SARS-CoV-2 Vaccination in Kidney Transplant Recipients—Stratified Analysis of the Humoral Immune Response
Authors: Lammert Alexander , Schnuelle Peter , Rabenau Holger F. , Ciesek Sandra , Krämer Bernhard K. , Göttmann Uwe , Drüschler Felix , Keller Christine , Rose Daniela , Blume Carsten , Thomas Michael , Kohmer Niko , Lammert Anne
Published: October 2022

Background.

Kidney transplant recipients are at increased risk of SARS-CoV-2 infection and a more severe course of COVID-19.

Methods.

We conducted a quantitative serologic testing of antibodies specific for the wild type of SARS-CoV-2 and the Omicron variant of concern before and after a third-dose vaccination, either mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) in a cohort of 103 stable kidney transplant recipients (median [range] age, 58 [22–84] y, 57 men [55.3%]).

Results.

Third-dose vaccination increased the seroconversion rate from 57.3% to 71.8%. However, despite a marked rise of the antibody concentrations after the booster, 55.4% and 11.6% only formed neutralizing antibodies against the SARS-CoV-2 wild type and Omicron, respectively. Treatment with mycophenolic acid/mycophenolate mofetil (in strata of the dose quartiles), advanced age, and‚ above all‚ impaired renal function (eGFR <60 mL/min) adversely influenced the humoral immunity regarding seroconversion and inhibition of the wild type of SARS-CoV-2.

Conclusions.

Apart from immunosuppressive therapy, the humoral vaccination response is largely affected by nonmodifiable factors in kidney transplant recipients. With the currently leading and clinically easier Omicron variant, this puts into perspective the strategy to significantly enhance the protective efficacy of the available vaccines by reducing or temporarily stopping proliferation inhibitors, not least considering the inherent rejection risk with a possible deterioration of graft function.
Is shape in the eye of the beholder? Assessing landmarking error in geometric morphometric analyses on live fish
Authors: Moccetti Paolo , Rodger Jessica R. , Bolland Jonathan D. , Kaiser-Wilks Phoebe , Smith Rowan , Nunn Andy D. , Adams Colin E. , Bright Jen A. , Honkanen Hannele M. , Lothian Angus J. , Newton Matthew , Joyce Domino A.
Published: October 2022

Geometric morphometrics is widely used to quantify morphological variation between biological specimens, but the fundamental influence of operator bias on data reproducibility is rarely considered, particularly in studies using photographs of live animals taken under field conditions. We examined this using four independent operators that applied an identical landmarking scheme to replicate photographs of 291 live Atlantic salmon (Salmo salarL.) from two rivers. Using repeated measures tests, we found significant inter-operator differences in mean body shape, suggesting that the operators introduced a systematic error despite following the same landmarking scheme. No significant differences were detected when the landmarking process was repeated by the same operator on a random subset of photographs. Importantly, in spite of significant operator bias, small but statistically significant morphological differences between fish from the two rivers were found consistently by all operators. Pairwise tests of angles of vectors of shape change showed that these between-river differences in body shape were analogous across operator datasets, suggesting a general reproducibility of findings obtained by geometric morphometric studies. In contrast, merging landmark data when fish from each river are digitised by different operators had a significant impact on downstream analyses, highlighting an intrinsic risk of bias. Overall, we show that, even when significant inter-operator error is introduced during digitisation, following an identical landmarking scheme can identify morphological differences between populations. This study indicates that operators digitising at least a sub-set of all data groups of interest may be an effective way of mitigating inter-operator error and potentially enabling data sharing.
Water Stress Effect on the Growth of Lettuce (Lactuca sativa) and Moth Plant (Araujia sericifera)
Authors: Adebanjo Oluwatosin , Aku Setordjie Elikplim , Li Rong Wei
Published: October 2022

Water is the medium through which nutrients are transported from the soil into plants’ systems. Without soil water, the growth and yield of plants are negatively affected. This experiment compares the effect of water stress on the biomass production and chlorophyll content of lettuce (Lactuca sativa) and a weed species - moth plant (Araujia sericifera).The seedlings of the two plant species each were given three irrigation levels: 100% (T1), 50% (T2) and 0% (T3) field capacity of the growth medium - a mixture of peat moss (SuliFlor SF1®) and perlite (Perlindustria®) at ratio (3:1). The treatments for each plant were replicated five times, and the treatment lasted six weeks. Data were collected on moisture content and salinity of growing media, fresh and dry weight of shoot and root of plants, height, number of leaves, leaf area and chlorophyll content of leaf. The result showed that the water stress conditions have no significant effect on the chlorophyll, plant height and number of leaves of the two plant species. While the moth plant was not significantly affected by the stress conditions, lettuce recorded a significant reduction in leaf area, and in the dry weight of root and aerial part of the totally stressed plants, this shows that lettuce growth is significantly affected by water stress. Hence, moth plant tolerates water stress conditions more than the lettuce plant and this result may also be indicative of the survival of the moth plant if it infests a lettuce field.
Macro-scale patterns in functional connectivity associated with ongoing thought patterns and dispositional traits
Authors: Hardikar Samyogita , Mckeown Bronte , Schaare H Lina , Wallace Raven Star , Xu Ting , Lauckner Mark , Valk Sofie , Margulies Daniel , Turnbull Adam , Bernhardt Boris , Vos de Wael Reinder , Villringer Arno , smallwood jonathan
Published: October 2022

Complex macro-scale patterns of brain activity that emerge during periods of wakeful rest provide insight into the organisation of neural function, how these differentiate individuals based on their traits, and the neural basis of different types of self-generated thoughts. Although brain activity during wakeful rest is valuable for understanding important features of human cognition, its unconstrained nature makes it difficult to disentangle neural features related to personality traits from those related to the thoughts occurring at rest. Our study builds on recent perspectives from work on ongoing conscious thought that highlight the interactions between three brain networks - ventral and dorsal attention networks, as well as the default mode network. We combined measures of personality with state-of-the-art indices of ongoing thoughts at rest and brain imaging analysis and explored whether this tripartite view can provide a framework within which to understand the contribution of states and traits to observed patterns of neural activity at rest. To capture macro-scale relationships between different brain systems, we calculated cortical gradients to describe brain organisation in a low dimensional space. Our analysis established that for more introverted individuals, regions of the ventral attention network were functionally more aligned to regions of the somatomotor system and the default mode network. At the same time, a pattern of detailed self-generated thought was associated with a decoupling of regions of dorsal attention from regions in the default mode network. Our study, therefore, establishes interactions between attention systems and the default mode network are important influences on ongoing thought at rest and highlights the value of integrating contemporary perspectives on conscious experience when understanding patterns of brain activity at rest.
Leveraging functional genomic annotations and genome coverage to improve polygenic prediction of complex traits within and between ancestries
Authors: Zheng Zhili , Liu Shouye , Sidorenko Julia , Yengo Loic , Turley Patrick , Ani Alireza , Wang Rujia , Nolte Ilja M. , Snieder Harold ,   Lifelines Cohort Study, Yang Jian , Wray Naomi R , Goddard Michael E , Visscher Peter M , Zeng Jian
Published: October 2022

We develop a new method, SBayesRC, that integrates GWAS summary statistics with functional genomic annotations to improve polygenic prediction of complex traits. Our method is scalable to whole-genome variant analysis and refines signals from functional annotations by allowing them to affect both causal variant probability and causal effect distribution. We analyse 28 traits in the UK Biobank using ∼7 million common SNPs and 96 annotations. SBayesRC improves prediction accuracy by 14% in European ancestry and by up to 33% in trans-ancestry prediction, compared to the baseline method SBayesR which does not use annotations, and outperforms state-of-the-art methods LDpred-funct, PolyPred-S and PRS-CSx by 12-15%. Investigation of factors affecting prediction accuracy identified a significant interaction between SNP density and annotation information, encouraging future use of whole-genome sequence variants for prediction. Functional partitioning analysis highlights a major contribution of evolutionary constrained regions to prediction accuracy and the largest per-SNP contribution from non-synonymous SNPs.
Cleavage of α-1,4-Glycosidic Linkages by the Glycosylphosphatidylinositol-Anchored α-Amylase AgtA Decreases the Molecular Weight of Cell Wall α-1,3-Glucan inAspergillus oryzae
Authors: Koizumi Ami , Miyazawa Ken , Ogata Makoto , Takahashi Yuzuru , Yano Shigekazu , Yoshimi Akira , Sano Motoaki , Hidaka Masafumi , Nihira Takanori , Nakai Hiroyuki , Kimura Satoshi , Iwata Tadahisa , Abe Keietsu
Published: October 2022

Aspergillusfungi contain α-1,3-glucan with a low proportion of α-1,4-glucan as a major cell wall polysaccharide. Glycosylphosphatidylinositol (GPI)-anchored α-amylases are conserved inAspergillusfungi. The GPI-anchored α-amylase AmyD inAspergillus nidulanshas been reported to directly suppress the biosynthesis of cell wall α-1,3-glucan but not to degrade itin vivo. However, the detailed mechanism of cell wall α-1,3-glucan biosynthesis regulation by AmyD remains unclear. Here we focused on AoAgtA, which is encoded by theAspergillus oryzae agtAgene, an ortholog of theA. nidulans amyDgene. Similar to findings inA. nidulans, agtAoverexpression inA. oryzaegrown in submerged culture decreased the amount of cell wall α-1,3-glucan and led to the formation of smaller hyphal pellets in comparison with the wild-type strain. We analyzed the enzymatic properties of recombinant (r)AoAgtA produced inPichia pastorisand found that it degraded soluble starch, but not linear bacterial α-1,3-glucan. Furthermore, rAoAgtA cleaved 3-α-maltotetraosylglucose with a structure similar to the predicted boundary structure between the α-1,3-glucan main chain and a short spacer composed of α-1,4-linked glucose residues in cell wall α-1,3-glucan. Interestingly, rAoAgtA randomly cleaved only the α-1,4-glycosidic bonds of 3-α-maltotetraosylglucose, indicating that AoAgtA may cleave the spacer in cell wall α-1,3-glucan. Consistent with this hypothesis, heterologous overexpression ofagtAinA. nidulansdecreased the molecular weight (MW) of cell wall α-1,3-glucan. Thesein vitroandin vivoproperties of AoAgtA suggest that GPI-anchored α-amylases can degrade the spacer α-1,4-glycosidic linkages in cell wall α-1,3-glucan before its insolubilization, and this spacer cleavage decreases the MW of cell wall α-1,3-glucanin vivo.
A pluripotent stem cell atlas of multilineage differentiation revealsTMEM88as a developmental regulator of mammalian blood pressure
Authors: Shen Sophie , Werner Tessa , Lukowski Samuel W. , Andersen Stacey , Sun Yuliangzi , Shim Woo Jun , Mizikovsky Dalia , Kobayashi Sakurako , Outhwaite Jennifer , Chiu Han Sheng , Chen Xiaoli , Chapman Gavin , Martin Ella M. M. A. , Xia Di , Pham Duy , Su Zezhuo , Kim Daniel , Yang Pengyi , Tan Men Chee , Sinniah Enakshi , Zhao Qiongyi , Negi Sumedha , Redd Meredith A. , Powell Joseph E. , Dunwoodie Sally L. , Tam Patrick P. L. , Bodén Mikael , Ho Joshua W. K. , Nguyen Quan , Palpant Nathan J.
Published: October 2022

Pluripotent stem cells provide a scalable approach to analyse molecular regulation of cell differentiation across multiple developmental lineage trajectories. In this study, we engineered barcoded iPSCs to generate an atlas of multilineage differentiation from pluripotency, encompassing a time-course of WNT-induced differentiation perturbed using modulators of WNT, BMP, and VEGF signalling. Computational mapping ofin vitrocell types toin vivodevelopmental lineages revealed a diversity of iPSC-derived cell types comprising mesendoderm lineage cell types including lateral plate and paraxial mesoderm, neural crest, and primitive gut. Coupling this atlas ofin vitrodifferentiation with Summary data-based Mendelian Randomisation analysis of human complex traits, we identify the WNT-inhibitor proteinTMEM88as a putative regulator of mesendodermal cell types governing development of diverse cardiovascular and anthropometric traits. Using genetic loss of function models, we show thatTMEM88is required for differentiation of diverse endoderm and mesoderm cell lineagesin vitroand thatTMEM88knockoutin vivoresults in a significant dysregulation of arterial blood pressure. This study provides an atlas of multilineage iPSC differentiation coupled with new molecular, computational, and statistical genetic tools to dissect genetic determinants of mammalian developmental physiology.
An RNA modification enzyme directly senses reactive oxygen species for translational regulation inEnterococcus faecalis
Authors: Lee Wei Lin , Sinha Ameya , Lam Ling Ning , Loo Hooi Linn , Liang Jiaqi , Ho Peiying , Cui Liang , Chan Cheryl Siew Choo , Begley Thomas , Kline Kimberly , Dedon Peter
Published: October 2022

Bacteria possess elaborate systems to manage reactive oxygen and nitrogen species (ROS) arising from exposure to the mammalian immune system and environmental stresses. Here we report the discovery of an ROS-sensing RNA-modifying enzyme that regulates translation of stress-response proteins in the gut commensal and opportunistic pathogenEnterococcus faecalis. We analyzed the tRNA epitranscriptome ofE. faecalisin response to reactive oxygen species (ROS) or sublethal doses of ROS-inducing antibiotics and identified large decreases in N2-methyladenosine (m2A) in both 23S ribosomal RNA and transfer RNA. This we determined to be due to ROS-mediated inactivation of the Fe-S cluster-containing methyltransferase, RlmN. Genetic knockout of RlmN gave rise to a proteome that mimicked the oxidative stress response, with increased levels of superoxide dismutase and decreased virulence proteins. While tRNA modifications are established to be dynamic for fine-tuning translation, here we report the first instance of a dynamically regulated, environmentally responsive rRNA modification. These studies lead to model in which RlmN serves as a redox-sensitive molecular switch, directly relaying oxidative stress to modulating translation through the rRNA and the tRNA epitranscriptome, revealing a new paradigm for understanding direct regulation of the proteome by RNA modifications.
IRE-1α is a key switch of pyroptosis and necroptosis in mice by dominating Gasdermin D
Authors: Zeng Xin , Zheng Qing , Li Deyong , Li Yumeng , Xu Qing , Liu Xiaohong , Zhu Min , Liu Wen , Li Lan , Lu Yanrong , Cheng Jingqiu , Chen Younan
Published: October 2022

Necroptosis and pyroptosis are lytic and inflammatory types of programmed cell death that require the membrane destruction predominantly driven by the mixed lineage kinase domain-like (MLKL) and gasdermin D (GSDMD) proteins, respectively. However, the crosstalk between them remains largely unknown. Here, our research discloses that endoplasmic reticulumn transmembrane protein inositol-requiring enzyme-1α (IRE-1α) is a potential modulator of both necroptosis and pyroptosis, paricularly in liver pathology. Interestingly, enhanced expression of IRE-1α triggers hepatic pyroptosis, while defective IRE-1α level activates hepatic necroptosis, and both processes are closed related to the activity of GSDMD in mice. To elucidate unknown crosstalk, by using pharmacological and genetic methods, we first demonstrated that IRE-1α suppresses necroptosis by promoting the expression of GSDMD and cleaves caspase-8 and by inhibiting the expression of receptor-interacting serine/threonine-protein kinase 1 (RIPK1), RIPK3 and MLKL. Unexpectedly, excess IRE-1α initiates pyroptosis by increasing GSDMD and NLRP3 levels. Our work clearly provides insight into the modulation of IRE-1α to dominate necroptosis and pyroptosis and suggests that IRE-1α may be a promising therapeutic target for drug discovery in both types of tissue injuries.
Taxonomy of introns, their evolution, and the role of minor introns in stress response
Authors: Olthof Anouk M , Schwoerer Charles F , Weber Audrey L , Arokiadhas Iswarya , Doggett Karen , Mieruszynski Stephen , Cnaani Avner , Heath Joan K , Biran Jakob , Kanadia Rahul N
Published: October 2022

Despite the high conservation of minor introns across eukaryotic supergroups, specific lineages have completely lost minor intron splicing, which has raised questions about their evolution and purpose. Addressing these questions requires identification of the introns that are affected by minor spliceosome inhibition. To this end, we applied principles of Linnaean taxonomy combined with position-weight matrices to produce five intron classes: minor, minor-like, hybrid, major-like and major. We classified introns across the genomes of 263 species of six eukaryotic supergroups, which can be viewed at the Minor Intron Database (MIDB). Transcriptomic analysis revealed that ∼40% of the minor introns are responsive to minor spliceosome inhibition, while an additional 5% of the minor-like and hybrid introns are also affected. We propose that minor-like introns represent an intermediate in the conversion of minor to major introns and uncover the importance of a guanine at the −1 position of the 5’ splice site in facilitating this shift in spliceosome dependence. Finally, we find that minor introns are aberrantly spliced in fish and plants upon cold stress, thereby providing a potential explanation for their high degree of conservation in these lineages.
Expression ofMicrocystisbiosynthetic gene clusters in natural populations suggests temporally dynamic synthesis of novel and known secondary metabolites in western Lake Erie
Authors: Yancey Colleen E. , Yu Fengan , Tripathi Ashootosh , Sherman David H. , Dick Gregory J.
Published: October 2022

Microcystisspp. produces diverse secondary metabolites within freshwater cyanoHABs around the world. In addition to the biosynthetic gene clusters (BGCs) encoding known compounds,Microcystisgenomes harbor numerous BGCs of unknown function, indicating its poorly understood chemical repertoire. While recent studies show thatMicrocystisproduces several metabolites in the lab and field, little work has focused on analyzing the abundance and expression of its broader suite of BGCs during cyanoHAB events. Here, we use metagenomic and metatranscriptomic approaches to track the relative abundance ofMicrocystisBGCs and their transcripts throughout the 2014 western Lake Erie cyanoHAB. Results indicate the presence of several transcriptionally active BGCs that are predicted to synthesize both known and novel secondary metabolites. The abundance and expression of these BGCs shifted throughout the bloom, with transcript abundance levels correlating with temperature, nitrate and phosphorus concentrations, and the abundance of co-occurring predatory and competitive eukaryotic microorganisms, suggesting the importance of both abiotic and biotic controls in regulating expression. This work highlights the need for understanding the chemical ecology and potential risks to human and environmental health posed by secondary metabolites that are produced but unmonitored, as well as the potential discovery of pharmaceutical compounds from cyanoHAB-derived BGCs.

Originality-Statement of Significance

Microcystis spp. dominate cyanobacterial harmful algal blooms (cyanoHABs) worldwide and pose significant threats to water quality through the production of numerous secondary metabolites, many of which are toxic. While the toxicity and biochemistry of microcystins and several other compounds have been well studied, the broader suite of secondary metabolites produced byMicrocystisremains poorly understood, leaving gaps in our understanding of their impacts on ecology, human and ecosystem health, or potential pharmaceutical application. In this study, we use metagenomic and transcriptomic datasets to examine the diversity of genes encoding synthesis of secondary metabolites in naturalMicrocystispopulations and assess their patterns of transcription in the context of biotic and abiotic conditions in western Lake Erie cyanoHABs. Our results reveal the presence of a large diversity of both known gene clusters that encode toxic secondary metabolites as well as novel ones that encode cryptic compounds. This research highlights the need for targeted studies of the secondary metabolite diversity in western Lake Erie, a vital freshwater source to the United States and Canada.
Reduction in RBD Binding Affinity to Glycosylated ACE2 is Entropic in Origin
Authors: Mugnai Mauro L. , Shin Sucheol , Thirumalai D.
Published: October 2022

The spike protein in the virus SARS-CoV-2 (the causative agent of COVID-19) recognizes the host cell by binding to the peptidase domain (PD) of the extracellular enzyme Angiotensin-converting Enzyme 2 (ACE2). A variety of carbohydrates could be attached to the six asparagines in the PD, resulting in a heterogeneous population of ACE2 glycoforms. Experiments have shown that the binding affinity of glycosylated and deglycosylated ACE2 to the virus is virtually identical. In most cases, the reduction in glycan size correlates with stronger binding, which suggests that volume exclusion, and hence entropic forces, determine the binding affinity. Here, we quantitatively test the entropy-based hypothesis by developing a lattice model for the complex between ACE2 and the SARS-CoV-2 spike protein Receptor-binding Domain (RBD). Glycans are treated as branched polymers with only volume exclusion, which we justify using all atom molecular dynamics simulations in explicit water. We show that the experimentally measured changes in the ACE2-RBD dissociation constants for a variety of engineered ACE2 glycoforms are well accounted for by our theory, thus affirming that ACE2 glycans have only a weak, entropic effect on RBD binding.