bluuebunny/crossref_metadata_2025 huggingface dataset:
Extra intravenous Ustekinumab reinduction is an effective optimization strategy for patients with refractory Crohn’s disease
Authors: Yao Jiayin , Peng Xiang , Zhong Yingkui , Su Tao , Bihi Adam , Zhao Junzhang , Liu Tao , Wang Wei , Hu Pinjin , Zhang Min , Zhi Min
Published: July 2023

Objectives

Ustekinumab (UST) optimization strategies, including shortening intervals and intravenous reinduction, should be administered to patients with partial or loss of respond. Evidence comparing these types of optimization treatments is limited. We evaluated the efficacy and safety of weight-based UST intravenous reinduction in patients with refractory Crohn’s disease (CD).

Methods

This was a single-center retrospective observational study. Optimization strategies were designed for patients showing partial or loss of response to standardized UST therapy. Clinical, biochemical, and endoscopic response and remission rate were determined by Crohn’s disease activity index (CDAI), C-reactive protein (CRP) levels, and SES-CD evaluation. UST trough concentrations were detected and adverse events were recorded.

Results

A total of 128 patients receiving UST optimization therapies were included, with 105 patients administered shortening intervals of q8w or q4w, and 23 receiving intravenous reinduction followed by subcutaneous q8w or q4w. The follow-up duration for the shortening interval and reinduction cohorts were 15.0 (10.0, 31.0) and 23.0 (13.0, 70.0) weeks, respectively. A significant CDAI delta variation pre-and post-treatment could be found between groups [17.0 (−4.4, 65.9) vs. 69.0(10.7, 151.0), p = 0.013]. the trough concentration of UST increased [2.5 (1.3, 5.3) vs. 1.1 (0.5, 2.3), p = 0.001] after intravenous reinduction. Clinical and endoscopic remission were achieved in 69.6 and 31.8% of patients in the intravenous reinduction cohort, and 62.9 and 22.2% of patients in the shortening interval cohort, respectively. No significant difference was found between groups regarding safety.

Conclusion

Intravenous reinduction brought about favorable recapture of clinical and endoscopic remission, and should have significant priority over the strategy of merely shortening drug intervals, which should be launched before switching to other biologics targeting different inflammatory pathways.

Clinical Trial Registration: identifier NCT04923100. https://classic.clinicaltrials.gov/ct2/show/NCT04923100?id=04923100&draw=2&rank=1
Global trends of interstitial lung diseases from 1990 to 2019: an age–period–cohort study based on the Global Burden of Disease study 2019, and projections until 2030
Authors: Zeng Qi , Jiang Depeng
Published: July 2023

Background

Interstitial lung diseases (ILDs) are indispensable components of chronic respiratory diseases and global health challenges. We aimed to explore the global long-term changes in the prevalence, mortality, and disability-adjusted life years (DALYs) of ILDs; investigate the independent effect of age, period, and cohort; and project the disease burden over the next decade.

Methods

Data were retrieved from the Global Burden of Disease (GBD) database 2019. The joinpoint regression model was used to calculate the average annual percent change (AAPC). An age–period–cohort (APC) analysis was employed to measure the independent effect of age, period, and cohort. The Bayesian age–period–cohort (BAPC) model was used to project the global epidemiological trends until 2030.

Results

From 1990 to 2019, the age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), and age-standardized disability-adjusted life years (DALYs) rate (ASDR) of interstitial lung disease and pulmonary sarcoidosis (ILD) slightly increased from 52.66 per 100,000 [95% uncertainty interval (UI) 44.49 to 61.07] to 57.62 per 100,000 (95% UI 49.42 to 65.67), from 1.76 per 100,000 (95% UI 1.41 to 2.22) to 2.17 per 100,000 (95% UI 1.5 to 2.62), and from 41.57 per 100,000 (95% UI 33.93 to 51.92) to 46.45 per 100,000 (95% UI 35.12 to 54.98), whereas the ASPR, ASMR, and ASDR of pneumoconiosis decreased. High social-demographic index (SDI) regions possessed the highest ASPR, whereas low-middle SDI regions had the highest ASMR and ASDR, followed by low-SDI regions in ILD. Middle-SDI regions reported the highest ASPR, ASMR, and ASDR in pneumoconiosis. The age effect showed that the rate ratio (RR) was high in older adults. Period effect indicated that the RR of prevalence increased over time, whereas the RR of mortality and DALYs decreased in men but increased in women. The cohort effect exhibited that the more recent birth cohort had a higher RR than the previous cohort in prevalence. We projected that ASPR, ASMR, and ASDR would stabilize with little variation over the next decade.

Conclusion

The global burden of ILDs remains relatively severe, especially among older adults, in low- and middle-SDI regions. Effective measurements are expected to improve this situation.
Systematic optimization of fermentation conditions for in vitro fermentations with fecal inocula
Authors: Poppe Jonas , Vieira-Silva Sara , Raes Jeroen , Verbeke Kristin , Falony Gwen
Published: July 2023

In vitro fermentation strategies with fecal inocula are considered cost-effective methods to gain mechanistic insights into fecal microbiota community dynamics. However, all in vitro approaches have their limitations due to inherent differences with respect to the in vivo situation mimicked, introducing possible biases into the results obtained. Here, we aimed to systematically optimize in vitro fermentation conditions to minimize drift from the initial inoculum, limit growth of opportunistic colonizers, and maximize the effect of added fiber products (here pectin) when compared to basal medium fermentations. We evaluated the impact of varying starting cell density and medium nutrient concentration on these three outcomes, as well as the effect of inoculation with fresh vs. stored fecal samples. By combining GC–MS metabolite profiling and 16 s rRNA gene-based amplicon sequencing, we established that starting cell densities below 1010 cells/ml opened up growth opportunities for members the Enterobacteriaceae family. This effect was exacerbated when using fecal samples that were stored frozen at −80°C. Overgrowth of Enterobacteriaceae resulted in lowered alpha-diversity and larger community drift, possibly confounding results obtained from fermentations in such conditions. Higher medium nutrient concentrations were identified as an additional factor contributing to inoculum community preservation, although the use of a less nutrient dense medium increased the impact of fiber product addition on the obtained metabolite profiles. Overall, our microbiome observations indicated that starting cell densities of 1010 cells/ml limited opportunities for exponential growth, suppressing in vitro community biases, whilst metabolome incubations should preferably be carried out in a diluted medium to maximize the impact of fermentable substrates.
High frequency of Lamivudine and Telbivudine resistance mutations in hepatitis B virus isolates from human immunodeficiency virus co-infected patients on highly active antiretroviral therapy in Bucaramanga, Colombia
Authors: Bautista-Amorocho Henry , Silva-Sayago Jorge Alexander , Picón-Villamizar Jirehl
Published: July 2023

Hepatitis B virus (HBV) antiviral Resistance-Associated Mutations (RAMs) in human immunodeficiency virus (HIV) coinfected patients undergoing highly active antiretroviral therapy (HAART) are complex and incompletely understood. We aimed to determine the prevalence of HBV coinfection, HBV genotypes, and RAMs in a cohort of people living with HIV (PLWH) in the northeastern region of Colombia. This cross-sectional study was carried out between February 2013 and February 2014. Virological, immunological and HAART data were collected from clinical records. In-house nested PCR and Sanger sequencing of the HBV pol gene were used to identify coinfections, genotypes, RAMs and HBV s antigen (HBsAg) escape mutants. Among 275 PLWH, HBV coinfection was confirmed in 32 patients (11.6%), of whom nine (28.2%) were HBsAg positive (active hepatitis B), and 23 (71.8%) were occult hepatitis B infections (OBI). All HBV sequences (n = 23) belonged to the genotype F3. Among HIV/HBV coinfections, 71.9% had CD4+ T cell counts above 200 cells/mm3 and 37.5% had undetectable HIV viral loads. The RAMs rtL80I, rtL180M, and rtM204V, which confer resistance to Lamivudine/Telbivudine and partially resistant to Entecavir, were found in all HBV isolates. An unknown rt236Y mutation to Tenofovir was also identified. Most patients under HAART received first-generation HBV antiviral therapy with a low genetic barrier to resistance. Antiviral Drug-associated Potential Vaccine-escape Mutations (ADAPVEMs) in the S gene were observed in all isolates ranging from 1–20 amino acid substitutions. However, no vaccine escape mutants were detected. In Conclusion, these findings highlight the importance of HBV molecular screening, antiviral resistance monitoring and new guidelines for PLWH to overcome RAMs and prevent HBV-related liver disease.
Microbial diversity in Antarctic Dry Valley soils across an altitudinal gradient
Authors: Mashamaite Lefentse , Lebre Pedro H. , Varliero Gilda , Maphosa Silindile , Ortiz Max , Hogg Ian D. , Cowan Don A.
Published: July 2023

Introduction

The Antarctic McMurdo Dry Valleys are geologically diverse, encompassing a wide variety of soil habitats. These environments are largely dominated by microorganisms, which drive the ecosystem services of the region. While altitude is a well-established driver of eukaryotic biodiversity in these Antarctic ice-free areas (and many non-Antarctic environments), little is known of the relationship between altitude and microbial community structure and functionality in continental Antarctica.

Methods

We analysed prokaryotic and lower eukaryotic diversity from soil samples across a 684 m altitudinal transect in the lower Taylor Valley, Antarctica and performed a phylogenic characterization of soil microbial communities using short-read sequencing of the 16S rRNA and ITS marker gene amplicons.

Results and Discussion

Phylogenetic analysis showed clear altitudinal trends in soil microbial composition and structure. Cyanobacteria were more prevalent in higher altitude samples, while the highly stress resistant Chloroflexota and Deinococcota were more prevalent in lower altitude samples. We also detected a shift from Basidiomycota to Chytridiomycota with increasing altitude. Several genera associated with trace gas chemotrophy, includingRubrobacterandOrnithinicoccus, were widely distributed across the entire transect, suggesting that trace-gas chemotrophy may be an important trophic strategy for microbial survival in oligotrophic environments. The ratio of trace-gas chemotrophs to photoautotrophs was significantly higher in lower altitude samples. Co-occurrence network analysis of prokaryotic communities showed some significant differences in connectivity within the communities from different altitudinal zones, with cyanobacterial and trace-gas chemotrophy-associated taxa being identified as potential keystone taxa for soil communities at higher altitudes. By contrast, the prokaryotic network at low altitudes was dominated by heterotrophic keystone taxa, thus suggesting a clear trophic distinction between soil prokaryotic communities at different altitudes. Based on these results, we conclude that altitude is an important driver of microbial ecology in Antarctic ice-free soil habitats.
Rhizospheric bacteria: the key to sustainable heavy metal detoxification strategies
Authors: Joshi Samiksha , Gangola Saurabh , Bhandari Geeta , Bhandari Narendra Singh , Nainwal Deepa , Rani Anju , Malik Sumira , Slama Petr
Published: July 2023

The increasing rate of industrialization, anthropogenic, and geological activities have expedited the release of heavy metals (HMs) at higher concentration in environment. HM contamination resulting due to its persistent nature, injudicious use poses a potential threat by causing metal toxicities in humans and animals as well as severe damage to aquatic organisms. Bioremediation is an emerging and reliable solution for mitigation of these contaminants using rhizospheric microorganisms in an environmentally safe manner. The strategies are based on exploiting microbial metabolism and various approaches developed by plant growth promoting bacteria (PGPB) to minimize the toxicity concentration of HM at optimum levels for the environmental clean-up. Rhizospheric bacteria are employed for significant growth of plants in soil contaminated with HM. Exploitation of bacteria possessing plant-beneficial traits as well as metal detoxifying property is an economical and promising approach for bioremediation of HM. Microbial cells exhibit different mechanisms of HM resistance such as active transport, extra cellular barrier, extracellular and intracellular sequestration, and reduction of HM. Tolerance of HM in microorganisms may be chromosomal or plasmid originated. Proteins such as MerT and MerA of mer operon and czcCBA, ArsR, ArsA, ArsD, ArsB, and ArsC genes are responsible for metal detoxification in bacterial cell. This review gives insights about the potential of rhizospheric bacteria in HM removal from various polluted areas. In addition, it also gives deep insights about different mechanism of action expressed by microorganisms for HM detoxification. The dual-purpose use of biological agent as plant growth enhancement and remediation of HM contaminated site is the most significant future prospect of this article.
Digital in-memory stochastic computing architecture for vector-matrix multiplication
Authors: Agwa Shady , Prodromakis Themis
Published: July 2023

The applications of the Artificial Intelligence are currently dominating the technology landscape. Meanwhile, the conventional Von Neumann architectures are struggling with the data-movement bottleneck to meet the ever-increasing performance demands of these data-centric applications. Moreover, The vector-matrix multiplication cost, in the binary domain, is a major computational bottleneck for these applications. This paper introduces a novel digital in-memory stochastic computing architecture that leverages the simplicity of the stochastic computing for in-memory vector-matrix multiplication. The proposed architecture incorporates several new approaches including a new stochastic number generator with ideal binary-to-stochastic mapping, a best seeding approach for accurate-enough low stochastic bit-precisions, a hybrid stochastic-binary accumulation approach for vector-matrix multiplication, and the conversion of conventional memory read operations into on-the-fly stochastic multiplication operations with negligible overhead. Thanks to the combination of these approaches, the accuracy analysis of the vector-matrix multiplication benchmark shows that scaling down the stochastic bit-precision from 16-bit to 4-bit achieves nearly the same average error (less than 3%). The derived analytical model of the proposed in-memory stochastic computing architecture demonstrates that the 4-bit stochastic architecture achieves the highest throughput per sub-array (122 Ops/Cycle), which is better than the 16-bit stochastic precision by 4.36x, while still maintaining a small average error of 2.25%.
Outcome after intracranial hemorrhage under dabigatran and reversal with idarucizumab versus under vitamin-K-antagonists – the RIC-ICH study
Authors: Kuklik Nils , Hüsing Anika , Stang Andreas , Brinkmann Marcus , Eschenfelder Christoph C. , Weimar Christian , Diener Hans-Christoph
Published: July 2023

Background

Intracranial hemorrhage (ICH) is a rare but serious side effect associated with the use of oral anticoagulants, such as dabigatran. The specific reversal agent for dabigatran, idarucizumab, is available for the management of individuals with ICH. The aim of this study was to provide real-world evidence on patients with ICH and effective treatment with dabigatran and reversal with idarucizumab in clinical routine compared to those under effective treatment with vitamin-K-antagonist (VKA).

Methods

Registration of Idarucizumab for Patients with IntraCranial Hemorrhage (RIC-ICH) is a non-interventional study conducted in 22 German stroke units that prospectively enrolled dabigatran patients treated with idarucizumab. Retrospective data from VKA patients served as reference population. Main objective was in-hospital mortality. Further objectives included change in bleeding volume, stroke severity, and functional status.

Result

In-hospital mortality was 26.7% in 15 dabigatran and 27.3% in 88 VKA patients (hazard ratio 1.00, 95% CI 0.29–2.60). In patients with bleeding volume > 60 ml, mortality was lower in the dabigatran group (N = 6, 33%) compared to the VKA group (N = 15, 67%; HR 0.24, 95% CI 0.04–0.96). No differences were observed in secondary endpoints between dabigatran and VKA patients.

Conclusion

These results, based on data from routine clinical practice, suggest that in-hospital mortality after idarucizumab treatment is comparable to that in patients pretreated with VKA. Due to the low precision of estimates, the results must be interpreted with caution.
Changes in functional connectivity among vestibulo-visuo-somatosensory and spatial cognitive cortical areas in persistent postural-perceptual dizziness: resting-state fMRI studies before and after visual stimulation
Authors: Yagi Chihiro , Morita Yuka , Yamagishi Tatsuya , Ohshima Shinsuke , Izumi Shuji , Takahashi Kuniyuki , Watanabe Masaki , Itoh Kosuke , Suzuki Yuji , Igarashi Hironaka , Horii Arata
Published: July 2023

Introduction

Persistent postural-perceptual dizziness (PPPD) is a functional chronic vestibular syndrome with symptom exacerbation by upright posture, motion, and complex visual stimuli. Among these exacerbating factors, visual exacerbation is the most specific characteristic of PPPD requiring further investigation. We hypothesized that stimulus-induced changes occur in the functional connectivity (FC) rather than simple neural activation that is involved in visual stimulation. The present study aimed to identify the neural basis of PPPD by investigating FC before and after visual stimulation.

Methods

Eleven patients with PPPD and 11 age- and sex-matched healthy controls (HCs) underwent resting-state fMRI (rs-fMRI) before and after task-based fMRI with visual stimuli.

Results

At pre-stimulus, FC between the vestibular cortex and visual areas was low, while that between the somatosensory and visual areas was high in PPPD compared with that in HCs. FC between the visuospatial (parahippocampal gyrus) and spatial cognitive areas (inferior parietal lobule) was elevated in PPPD even in the pre-stimulus condition, which no longer increased at post-stimulus as observed in HCs. In the post-stimulus condition, FC between the visual and spatial cognitive areas and that between the visual and prefrontal areas increased compared with that in the pre-stimulus condition in PPPD. Task-based fMRI demonstrated that no brain regions showed different activities between the HC and PPPD groups during visual stimulation.

Discussion

In PPPD, vestibular inputs may not be fully utilized in the vestibulo-visuo-somatosensory network. Given that the FC between visuospatial and spatial cognitive areas increased even in HCs after visual stimuli, elevated status of this FC in combination with the high FC between the somatosensory and visual areas would be involved in the visual exacerbation in PPPD. An increase in FC from the visual areas to spatial cognitive and prefrontal areas after visual stimuli may account for the prolonged symptoms after visual exacerbation and anxious status in PPPD.
Value of a preoperative prognostic nutritional index for the prognostic evaluation of gastric neuroendocrine carcinoma patients
Authors: Wei Jiangpeng , Lu Ju , Jia Hanxiang , Yang Xisheng , Guo Xin , Liu Jinqiang , Li Xiaohua
Published: July 2023

Objective

To study the value of Onodera’s prognostic nutrition index (PNI) in patients with gastric neuroendocrine cancer (G-NEC).

Methods

The clinical data on 148 cases of G-NEC presented between March 2010 and April 2022 were retrospectively analyzed. The relationship between the clinical characteristics of the patients and PNI was analyzed. Optimal PNI cutoff values for G-NEC prognosis prediction were calculated using the X-tile software. The survival curves were created using the Kaplan–Meier method. A Cox proportional hazards model was also established to identify independent prognostic factors that impact the prognosis of patients with G-NEC.

Results

The median overall survival (OS) rate was 30 months (range 6–127 months), and the OS rates at 1, 3 and 5 years were 89.2, 71.6 and 68.2%, respectively. The mean PNI of the 148 patients before the operation was 49.5 ± 8.0. The mean PNI of patients with anemia (p < 0.001) and abnormal carcinoembryonic antigen (p = 0.039) was significantly lower than that of patients without such comorbidities. The mean PNI of patients with Stage III tumors (p < 0.001) and postoperative complications was significantly lower (p = 0.005). PNI optimal cutoff values were 50 (p < 0.001). Based on the cut-off value of the PNI, these patients were divided into a PNI-high group (PNI ≥ 50.0, n = 77) and a PNI-low group (PNI < 50.0, n = 71). The PNI-high group had a significantly better 5-years OS rate compared with the PNI-low group (76.6% vs. 59.2%, χ2 = 14.7, p < 0. 001). Multivariate analysis demonstrated that PNI and pathological stage were independent prognostic factors for patients with G-NEC. In the subgroup analysis, OS rates were significantly lower in the PNI-low group than in the PNI-high group among patients with stage I and stage III of the disease.

Conclusion

The PNI is a simple and useful marker for predicting long-term outcomes in G-NEC patients regardless of tumor stage. Based on our results, we suggest that PNI should be included in routine assessments of patients with G-NEC.
A pregnant woman with a giant bilateral parietal hemangiopericytoma underwent multiple surgeries and radiotherapy: a case report and literature review
Authors: Wu Yingxi , Xue Yafei , Wang Xinqi , Li Junting , Qu Yan , Zhao Tianzhi
Published: July 2023

Intracranial hemangiopericytoma is a rare invasive tumor originating from mesenchymal fibroblasts and is prone to local recurrence and distant metastasis. This study reports a case of a 27-year-old woman who presented with severe headache, nausea and vomiting for two weeks at thirty-three weeks of gestation. Cranial magnetic resonance imaging (MRI) demonstrated a giant lesion in the bilateral parietal lobe with a size of 5.12x9.19x6.03 cm and severe edema in the surrounding brain tissue. The patient underwent four operations and 3 gamma knife radiosurgery procedures and is recovering well now. The histopathology findings showed hemangiopericytoma and STAT6 and CD34 positivity after the first and second surgeries. Because of tumor progression, the patient received gamma knife radiosurgery at 1, 3, and 4 years after the first operation. Total tumor resection was achieved in the fourth surgery. Nevertheless, the patient showed malignant transformation to from low-grade to high-grade hemangiopericytoma.
Next-generation sequencing-based detection in a breast MMPMN patient with EGFR T790M mutation: a rare case report and literature review
Authors: Lv Huiyun , Tian Aijuan , Zhao Shanshan , Zhao Jinbo , Song Chen
Published: July 2023

Multiple primary malignant neoplasms (MPMNs) are difficult to identify from the metastasis or recurrence of malignant tumors. Additionally, the genetic mutations in each primary tumor vary from each other; therefore, it is critical to explore potential abnormal genes. Next-generation sequencing (NGS) technology has emerged as a reliable approach for detecting mutated genes in primary tumors and can provide several targeted therapeutic options for patients with MPMNs. Here, we report a case of metachronous multiple primary malignant neoplasm (MMPMN) patient with primary ovarian and breast cancer. Targeted NGS genetic profiling revealed a rare EGFR T790M mutation in this patient’s primary breast tumor tissue, which has only been reported previously in breast cancer (BC). Based on the NGS results, osimertinib was recommended for this patient. Although this patient did not receive osimertinib because of gastrointestinal hemorrhage, this case highlights the significance of NGS technology in the diagnosis and treatment of MPMNs.
Impact of interval progression before autologous stem cell transplant in patients with multiple myeloma
Authors: Bao Alicia , Zhao Qiuhong , Kudalkar Ruchi , Rodriguez Jose , Sharma Nidhi , Bumma Naresh , Devarakonda Srinivas S. , Khan Abdullah M. , Umyarova Elvira , Rosko Ashley E. , Benson Don , Cottini Francesca
Published: July 2023

In transplant-eligible patients who undergo upfront autologous stem cell transplant (ASCT) for multiple myeloma (MM), standard practice is to treat with six to eight cycles of induction therapy followed by high-dose chemotherapy with ASCT. A gap between the end of induction and the day of ASCT exists to allow stem cell mobilization and collection. Despite attempts to limit the length of this interval, we noticed that some patients experience interval progression (IP) of disease between the end of induction therapy and the day of ASCT. We analyzed 408 MM patients who underwent ASCT between 2011 and 2016. The median length of the interval between end of induction and ASCT was 38 days. We observed that 26% of patients in the entire cohort and 23.6% of patients who received induction with bortezomib-lenalidomide-dexamethasone (VRD) experienced IP. These patients deepened their responses with ASCT, independently of induction regimen. In the entire cohort, IP was significantly associated with shorter PFS in the univariable analysis (Hazard Ratio, HR = 1.37, P = 0.022) but not in the multivariable analysis (HR = 1.14, P = 0.44). However, analyzing only patients who received VRD as induction, progression-free survival (PFS) remained inferior in both the univariable (HR = 2.02; P = 0.002) and the multivariable analyses (HR = 1.96; P = 0.01). T cells and natural killer (NK) cells are increasingly studied targets of immunomodulatory therapy, as immune dysfunction is known to occur in patients with MM. Peripheral blood from 35 MM patients were analyzed. At time of ASCT, patients with IP had significantly increased percentages of CD3+CD8+CD57+ CD28- (P = 0.05) and CD3+CD4+LAG3+ (P = 0.0022) T-cells, as well as less CD56bright and CD56dim NK cells bearing activated markers such as CD69, NKG2D, and CD226. These data suggest that IP can impact the length of response to ASCT; therefore, further studies on the management of these patients are needed.
Target identification and validation of the alpha7 nicotinic acetylcholine receptor as a potential therapeutic target in retinal disease
Authors: Linn David M.
Published: July 2023

The role of acetylcholine (ACh) in visual processing in the mammalian retina has been the focus of research for many decades. Pioneering work on the localization of ACh discovered that the neurotransmitter is synthesized and stored in a distinct subpopulation of amacrine (starburst) cells. It has been shown that ACh release is regulated to a low resting “tonic” level, much like what is observed at the neuromuscular junction (NMJ). If there were a dysfunction in the tonic release of ACh, might post-synaptic changes render the targets of ACh [i.e., retinal ganglion cells (RGCs)] vulnerable to disease? During my time at Pharmacia & Upjohn (PNU), selective nicotinic ACh receptor (nAChR) agonists (e.g., PNU-282987) were developed as a possible therapy for central nervous system (CNS) diseases. As RGCs are the main targets of neurodegeneration in glaucoma, could the activation of this target provide neuroprotection? In response to this question, experiments to identify alpha7 nAChRs in the retina (i.e., target ID studies) followed by “proof-of-concept” experiments were conducted. Target ID studies included binding studies with retinal homogenates, [125I]-alpha-bungarotoxin (α-BTX) autoradiography, and fluorescently tagged α-BTX binding in retinal slices. Imaging studies of intracellular calcium dynamics in the retinal slice were conducted. Reverse transcription-polymerase chain reaction (RT-PCR) analysis with alpha7 nAChR knockout mice using the “laser-capture microdissection” technique,in situhybridization studies, and RT-PCR analysis of the human retina were conducted. Collectively, these experiments confirmed the presence of alpha7 nAChRs on specific cells in the retina. “Proof-of-concept” neuroprotection studies demonstrated that PNU-282987 provided significant protection for RGCs. This protection was dose dependent and was blocked with selective antagonists. More recently, evidence for the generation of new RGCs has been reported with PNU-282987 in rodents. Interestingly, the appearance of new RGCs is more pronounced with eye-drop application than with intravitreal injection. One could postulate that this reflects the neurogenic activation of alpha7 receptors on the retinal pigment epithelium (RPE) (eye drops) vs. a neuroprotective effect on RGCs (injections). In conclusion, there does appear to be a cholinergic retinal “tone” associated with RGCs that could be utilized as a neuroprotective therapy. However, a distinct cholinergic neurogenic mechanism also appears to exist in the outer retina that could possibly be exploited to generate new RGCs lost through various disease processes.
A comprehensive review of summer savory (Satureja hortensis L.): promising ingredient for production of functional foods
Authors: Ejaz Afaf , Waliat Sadaf , Arshad Muhammad Sajid , Khalid Waseem , Khalid Muhammad Zubair , Rasul Suleria Hafiz Ansar , Luca Marian-Ilie , Mironeasa Costel , Batariuc Ana , Ungureanu-Iuga Mădălina , Coţovanu Ionica , Mironeasa Silvia
Published: July 2023

This review aims to measure the different aspects of summer savory including biological activity, medicinal properties, nutritional value, food application, prospective health benefits, and its use as an additive in broiler feed. Furthermore, toxicity related to this is also overviewed. Summer savory leaves are abundant in total phenolic compounds (rosmarinic acid and flavonoids) that have a powerful antioxidant impact. Rosmarinic (α-O-caffeoyl-3,4-dihydroxy-phenyl lactic) acid has been identified in summer savory as a main component. According to phytochemical investigations, tannins, volatile oils, sterols, acids, gums, pyrocatechol, phenolic compounds, mucilage, and pyrocatechol are the primary compounds of Satureja species. Summer savory extract shows considerable biological potential in antioxidant, cytotoxic, and antibacterial assays. Regarding antioxidant activity, summer savory extract displays an inhibitory effect on lipid peroxidation. Summer savory also has Fe (III) reductive and free radical scavenging properties and contains minerals and vitamins. Summer savory has important biological properties, including antimicrobial activity and antioxidant activity, and protective effects against Jurkat T Cells, Alzheimer’s disease, cancer, infection, cardiovascular diseases, diabetes, and cholesterol. The leaves and stems of this plant are employed in the food, feed, and pharmacological industries due to their antioxidant properties and substantial nutritional content. Conclusively, summer savory is widely considered beneficial for human health due to its versatile properties and medicinal use.
The efficacy and safety of cuttlebone for lowering serum phosphate in patients with end-stage renal disease: a meta-analysis of randomized controlled trials
Authors: Chen Hsiao-Tien , Hung Kuo-Chuan , Hsu Chin-Wei , Chen Jui-Yi , Liu Chien-Cheng , Chen I-Wen , Sun Cheuk-Kwan
Published: July 2023

Background: The efficacy of cuttlebone for treating hyperphosphatemia in patients with end-stage renal disease and its safety remained unclear.

Methods: Randomized controlled trials comparing the efficacy of cuttlebone with conventional interventions were retrieved from MEDLINE, EMBASE, Cochrane Library, Airiti Library, and other major Chinese databases until 1 February 2023. The primary outcome was circulating phosphate concentration, while secondary outcomes included circulating calcium and intact parathyroid hormone levels, calcium–phosphorus product, and treatment-related side-effects.

Results: Analysis of nine studies published between 2000 and 2019 including 726 participants showed a lower circulating phosphate concentration in the cuttlebone group than in controls [mean difference (MD) = −0.23, 95% CI: −0.39 to −0.06, p = 0.006, I2 = 94%, 726 patients] and a dose-dependent effect of cuttlebone against hyperphosphatemia. Therapeutic benefits were noted after both short-term (1–2 months) and long-term (3–6 months) treatments. Besides, patients receiving hemodialysis showed a better response to cuttlebone than those receiving peritoneal dialysis. There was no difference in circulating calcium level (mean difference = 0.03, 95% CI: −0.01 to 0.07, p = 0.17, I2 = 34%, 654 patients), while patients receiving cuttlebone showed lower circulating iPTH level and calcium-phosphorus product (MD = −43.63, 95% CI: −74.1 to −13.16, p = 0.005, I2 = 76%, 654 patients), (MD = −0.38, 95% CI: −0.38 to −0.01, p = 0.04, I2 = 83%, 520 patients). No difference in the risks of constipation, gastrointestinal discomfort, and elevated blood calcium was noted between the two groups.

Conclusion: Compared with conventional phosphate-binding agents, cuttlebone more efficiently suppressed hyperphosphatemia with a dose-dependent effect. The limited number of included studies warrants further clinical investigations to verify our findings.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier CRD42023396300.
The development of a zero-dimensional collisional-radiative model for interpreting plasma emission in low temperature divertor plasmas in tokamaks
Authors: Fox-Widdows Ella , Bowden Mark D. , Hoshino Kazuo , Hatayama Akiyoshi , Osawa Ryoko , Tsubotani Yuka
Published: July 2023

Collisional-radiative models are commonly used to analyse atomic and molecular processes in low temperature plasmas by determining the distribution functions of excited states as functions of various plasma parameters. This paper outlines the improvements to a zero-dimensional collisional-radiative model, developed at Keio University, for purposes relevant to the analysis of emission measurements in low temperature hydrogen plasmas. The extension of this 0D model centres on the inclusion of additional molecular species and reactions, a calculation of emission intensity in order to directly compare with experimental work, and the addition of a simple wall model to allow for a deeper understanding of recycling of atoms and molecules in low temperature plasmas close to plasma facing components in fusion machines. Results from the improved model are then compared with both an existing CR model for benchmarking and experimental emission spectroscopy data from an inductively-coupled plasma device at the University of Liverpool. These results show how the developments to the model have increased the relevance to experimental plasmas, such as those in the power exhaust regions of fusion machines, with the ratio of the Hβ/Hα line intensities outputted from the improved CR model mirroring more closely the emission measured experimentally in the ICP device.
Amplitude and phase noise in two-membrane cavity optomechanics
Authors: Marzioni Francesco , Rasponi Francesco , Piergentili Paolo , Natali Riccardo , Di Giuseppe Giovanni , Vitali David
Published: July 2023

Cavity optomechanics is a suitable field to explore quantum effects on macroscopic objects and develop quantum technology applications. A perfect control of the laser noise is required to operate the system in such extreme conditions necessary to reach the quantum regime. In this paper, we consider a Fabry–Perót cavity, driven by two laser fields, with two partially reflective SiN membranes inside it. We describe the effects of amplitude and phase noise on the laser introducing two additional noise terms in the Langevin equations of the system’s dynamics. Experimentally, we add an artificial source of noise on the laser. We calibrate the intensity of the noise, inject it into the system, and check the validity of the theoretical model. This procedure provides an accurate description of the effects of a noisy laser in the optomechanical setup and allows for quantifying the amount of noise.
Black sheep, dark horses, and colorful dogs: a review on the current state of the Gene Ontology with respect to iron homeostasis in Arabidopsis thaliana
Authors: Mai Hans-Jörg , Baby Dibin , Bauer Petra
Published: July 2023

Cellular homeostasis of the micronutrient iron is highly regulated in plants and responsive to nutrition, stress, and developmental signals. Genes for iron management encode metal and other transporters, enzymes synthesizing chelators and reducing substances, transcription factors, and several types of regulators. In transcriptome or proteome datasets, such iron homeostasis-related genes are frequently found to be differentially regulated. A common method to detect whether a specific cellular pathway is affected in the transcriptome data set is to perform Gene Ontology (GO) enrichment analysis. Hence, the GO database is a widely used resource for annotating genes and identifying enriched biological pathways in Arabidopsis thaliana. However, iron homeostasis-related GO terms do not consistently reflect gene associations and levels of evidence in iron homeostasis. Some genes in the existing iron homeostasis GO terms lack direct evidence of involvement in iron homeostasis. In other aspects, the existing GO terms for iron homeostasis are incomplete and do not reflect the known biological functions associated with iron homeostasis. This can lead to potential errors in the automatic annotation and interpretation of GO term enrichment analyses. We suggest that applicable evidence codes be used to add missing genes and their respective ortholog/paralog groups to make the iron homeostasis-related GO terms more complete and reliable. There is a high likelihood of finding new iron homeostasis-relevant members in gene groups and families like the ZIP, ZIF, ZIFL, MTP, OPT, MATE, ABCG, PDR, HMA, and HMP. Hence, we compiled comprehensive lists of genes involved in iron homeostasis that can be used for custom enrichment analysis in transcriptomic or proteomic studies, including genes with direct experimental evidence, those regulated by central transcription factors, and missing members of small gene families or ortholog/paralog groups. As we provide gene annotation and literature alongside, the gene lists can serve multiple computational approaches. In summary, these gene lists provide a valuable resource for researchers studying iron homeostasis in A. thaliana, while they also emphasize the importance of improving the accuracy and comprehensiveness of the Gene Ontology.
WeedNet-R: a sugar beet field weed detection algorithm based on enhanced RetinaNet and context semantic fusion
Authors: Guo Zhiqiang , Goh Hui Hwang , Li Xiuhua , Zhang Muqing , Li Yong
Published: July 2023

Accurate and dependable weed detection technology is a prerequisite for weed control robots to do autonomous weeding. Due to the complexity of the farmland environment and the resemblance between crops and weeds, detecting weeds in the field under natural settings is a difficult task. Existing deep learning-based weed detection approaches often suffer from issues such as monotonous detection scene, lack of picture samples and location information for detected items, low detection accuracy, etc. as compared to conventional weed detection methods. To address these issues, WeedNet-R, a vision-based network for weed identification and localization in sugar beet fields, is proposed. WeedNet-R adds numerous context modules to RetinaNet’s neck in order to combine context information from many feature maps and so expand the effective receptive fields of the entire network. During model training, meantime, a learning rate adjustment method combining an untuned exponential warmup schedule and cosine annealing technique is implemented. As a result, the suggested method for weed detection is more accurate without requiring a considerable increase in model parameters. The WeedNet-R was trained and assessed using the OD-SugarBeets dataset, which is enhanced by manually adding the bounding box labels based on the publicly available agricultural dataset, i.e. SugarBeet2016. Compared to the original RetinaNet, the mAP of the proposed WeedNet-R increased in the weed detection job in sugar beet fields by 4.65% to 92.30%. WeedNet-R’s average precision for weed and sugar beet is 85.70% and 98.89%, respectively. WeedNet-R outperforms other sophisticated object detection algorithms in terms of detection accuracy while matching other single-stage detectors in terms of detection speed.
The Norwegian CDI-III as an assessment tool for lexical and grammatical development in preschoolers
Authors: Holm Elisabeth , Hansen Pernille Bonnevie , Romøren Anna Sara H. , Garmann Nina Gram
Published: July 2023

Parental report instruments are a non-invasive way to assess children’s language development and have proved to give both valid and reliable results when used with children under the age of 2;6 (and in some cases up to 3). In this study we examine the newly developed Norwegian edition of a language assessment tool for older preschoolers: MacArthur-Bates Communicative Development Inventory III (CDI-III), investigating whether this parental report tool can be used for assessing the language of monolingual Norwegian-speaking children between 2;6 and 4 years. NCDI-III results for 100 children between 2;6 and 4.0 are presented. All sections were significantly intercorrelated. All sections except Pronunciation showed growth with age. Internal consistency was measured both in terms of Cronbach’s alpha and corrected item-scale correlation, and the results are discussed considering features of item difficulty distribution. Methodological considerations are discussed, as well as implications relevant both for possible later revisions and for CDI-III adaptations to new languages.
Physically real and virtual reality exposed line bisection response patterns: visuospatial attention allocation in virtual reality
Authors: Kállai János , Páll Tamás , Topa Kristóf , Zsidó András Norbert
Published: July 2023

Introduction

To understand the nature of hemispatial attention allocation in virtual reality (VR), a line bisection task (LBT) was administered both in a real environment and a virtual environment to assess the rate of pseudoneglect. The mental construction of real and virtual environments was assumed to increase visuospatial activity in right hemisphere-related cognitive processes; an alteration in the activity that manifests in the direction and rate of line bisection lateral error.

Methods

In the present study, fifty-one right-handed healthy college students were recruited. They performed a line bisection task in real and virtual environments.

Results

The obtained data showed that LBT errors in real and VR environments were correlated and individually consistent. Furthermore, a leftward LBT error was found in the physically real environment, however, in a VR the line bisection bias drifted towards the right hemispace. Participants with a lower right-handedness score showed a lower rate of left LBT bias in a real environment, but in VR, their LBT error showed a stronger rightwards error.

Discussion

Participants showed an individually consistent pattern in both real and VR environments, but VR-induced visuospatial reality construction was associated with rightward LBT bias in a virtual environment.
The decision-making in dribbling: a video analysis study of U10 soccer players’ skills and coaches’ quality evaluation
Authors: Iuliano Enzo , Bonavolontà Valerio , Ferrari Dafne , Bragazzi Nicola , Capasso Benito , Kuvačić Goran , De Giorgio Andrea
Published: July 2023

Introduction

Dribbling is an important soccer skill that, when effective, allows players to overcome opponents. It can provide a strong tactical advantage; for this reason, all of its components (sprint, speed, and ball control) are fundamental to the development of young players. Dribbling can also be considered a decision-making process, and due to its characteristics, it is not always easy to study ecologically. Using a video analysis study, this research aimed to determine whether dribbling skills, specifically dribbling choice (i.e., decision-making), were related to U10 soccer players’ quality.

Methods

Several outcomes measures, divided into three categories, were taken during video analyses: (i) measures related to the efficacy of dribbling skill; (ii) measures related to the ability of players without the ball to support the player in possession; and (iii) measures related to ball circulation. These data were retrospectively assessed to whether the coaches had formed the teams in training through an implicit knowledge of the players’ dribbling skills.

Results

The percentage of accurate dribbling (that is, the ability to perform correct passes after a successful dribble) was found to be the variable that coaches may have implicitly used in creating the three groups differentiated by technical skills (p < 0.05). In fact, this percentage was 12.9%, 24.0%, and 48.1% for the groups with lower, average, and higher technical skills, respectively.

Conclusion

Overall, the results demonstrate that dribbling accuracy has an important weight in the coach’s evaluation of the technical skills level of young soccer players.
Association between housework and the risk of dementia among older Chinese adults: a prospective cohort study
Authors: Wang Yuanlong , Luo Xinxin , Long Xiangyun , Shao Yuan , Zhang Song , Zhang Yingli , Wang Yongjun
Published: July 2023

Objectives

Physical activity (PA) is known to improve physical functioning and mental health and to reduce the incidence of dementia. However, studies of the effects of non-recreational PA on the incidence of dementia, especially in East Asian populations, remain limited. In this study, we evaluate the association of doing housework with the risk of dementia among participants in the Chinese Longitudinal Healthy Longevity Survey (CLHLS).

Methods

The analysis was conducted with data from 7,237 CLHLS participants age over 65 obtained in 2008/2009, 2011/2012, 2014, and 2018. The frequency of housework performance was classified into four groups. A Cox proportional-hazards model was used to examine the association of the baseline housework frequency with the incidence of dementia, with adjustment for demographic and socioeconomic characteristics and lifestyle and health conditions.

Results

The adjusted multivariate model showed that the incidence of dementia was lower among participants who did housework almost every day than among those who rarely or never did housework (hazard ratio = 0.49; 95% confidence interval, 0.39–0.61). The subgroup and sensitivity analyses yielded similar results.

Conclusion

A high frequency of housework performance was associated with a reduced incidence of dementia among older Chinese adults, especially those who did not exercise regularly. The encouragement of engagement in housework would be a cost-effective measure promoting healthy aging in the Chinese population.