bluuebunny/crossref_metadata_2025 huggingface dataset:
CSF oligoclonal IgG bands are not associated with ALS progression and prognosis
Authors: Klose Veronika , Jesse Sarah , Lewerenz Jan , Kassubek Jan , Dorst Johannes , Tumani Hayrettin , Ludolph Albert C. , Roselli Francesco
Published: May 2023

Introduction

Amyotrophic Lateral Sclerosis (ALS) is characterized by progressive motoneuron degeneration through cell autonomous and non-cell autonomous mechanisms; and the involvement of the innate and adaptive immune system has been hypothesized based on human and murine model data. We have explored if B-cell activation and IgG responses, as detected by IgG Oligoclonal bands (OCB) in serum and cerebrospinal fluid, were associated with ALS or with a subgroup of patients with distinct clinical features.

Methods

IgG OCB were determined in patients affected by ALS (n=457), Alzheimer Disease (n=516), Mild Cognitive Impairment (n=91), Tension-type Headache (n=152) and idiopathic Facial Palsy (n=94). For ALS patients, clinico-demographic and survival data were prospectively collected in the Register Schabia.

Results

The prevalence of IgG OCB is comparable in ALS and the four neurological cohorts. When the OCB pattern was considered (highlighting either intrathecal or systemic B-cells activation), no effect of OCB pattern on clinic-demographic parameters and overall. ALS patients with intrathecal IgG synthesis (type 2 and 3) were more likely to display infectious, inflammatory or systemic autoimmune conditions.

Discussion

These data suggest that OCB are not related to ALS pathophysiology but rather are a finding possibly indicative a coincidental infectious or inflammatory comorbidity that merits further investigation.
Differences in spontaneous speech fluency between Parkinson's disease and spinocerebellar ataxia type 3
Authors: dos Santos Vanessa Brzoskowski , Ayres Annelise , Kieling Maiara Laís Mallmann , Miglorini Elaine Cristina , Jardim Laura Bannach , Schumacher-Schuh Artur Francisco , Rieder Carlos Roberto de Mello , Castilhos Raphael Machado de , Spencer Kristie , Rothe-Neves Rui , Olchik Maira Rozenfeld
Published: May 2023

Background

The basal ganglia and cerebellum both have a role in speech production although the effect of isolated involvement of these structures on speech fluency remains unclear.

Objective

The study aimed to assess the differences in the articulatory pattern in patients with cerebellar vs. basal ganglia disorders.

Methods

A total of 20 individuals with Parkinson's disease (PD), 20 with spinocerebellar ataxia type 3 (SCA3), and 40 controls (control group, CG) were included. Diadochokinesis (DDK) and monolog tasks were collected.

Results

The only variable that distinguished SCA3 carriers from the CG was the number of syllables in the monolog, with SCA3 patients of a significantly lower number. For patients with PD, the number of syllables, phonation time, DDK, and monolog were significantly lower than for CG. Patients with PD were significantly worse compared to patients with SCA3 in the number of syllables and phonation time in DDK, and phonation time in monolog. Additionally, there was a significant correlation between the number of syllables in the monolog and the MDS-UPDRS III for participants with PD, and the Friedreich Ataxia Rating Scale for participants with SCA3 suggesting a relationship between speech and general motor functioning.

Conclusion

The monolog task is better at discriminating individuals with cerebellar vs. Parkinson's diseases as well as differentiating healthy control and was related to the severity of the disease.
The fibroblast growth factor system in cognitive disorders and dementia
Authors: Zhai Wujianwen , Zhang Tong , Jin Yujing , Huang Shijing , Xu Manman , Pan Juhua
Published: May 2023

Cognitive impairment is the core precursor to dementia and other cognitive disorders. Current hypotheses suggest that they share a common pathological basis, such as inflammation, restricted neurogenesis, neuroendocrine disorders, and the destruction of neurovascular units. Fibroblast growth factors (FGFs) are cell growth factors that play essential roles in various pathophysiological processes via paracrine or autocrine pathways. This system consists of FGFs and their receptors (FGFRs), which may hold tremendous potential to become a new biological marker in the diagnosis of dementia and other cognitive disorders, and serve as a potential target for drug development against dementia and cognitive function impairment. Here, we review the available evidence detailing the relevant pathways mediated by multiple FGFs and FGFRs, and recent studies examining their role in the pathogenesis and treatment of cognitive disorders and dementia.
Orientation selective stimulation with tetrahedral electrodes of the rat infralimbic cortex to indirectly target the amygdala
Authors: Gureviciene Irina , Laakso Hanne , Narvaez Omar , Paasonen Ekaterina , Lehto Lauri , Gurevicius Kestutis , Mangia Silvia , Michaeli Shalom , Gröhn Olli , Sierra Alejandra , Tanila Heikki
Published: May 2023

Introduction

Deep brain stimulation (DBS) is a rapidly developing therapeutic intervention with constantly expanding neurological and psychiatric indications. A major challenge for the approach is the precise targeting and limitation of the effect on the desired neural pathways. We have introduced a new approach, orientation selective stimulation (OSS) that allows free rotation of the induced electric field on a plane when using a probe with three parallel electrodes forming an equilateral triangle at the tip. Here, we expand the technique by introducing a tetrahedral stimulation probe that enables adjustment of the primary electric field direction freely at any angle in a 3D space around the stimulating probe. OSS in 3D will enable better targeting of the electric field according to the local brain anatomy. We tested its utility in a rat model of DBS for treatment-resistant depression. The stimulation directed to the subgenual anterior cingulate cortex (sgACC) has yielded dramatic improvement in individual patients suffering from therapy resistant depression, but no consistent benefit in larger series. This failure has been ascribed to the challenging anatomy of sgACC with several crossing neural tracts and individual differences in the local anatomy.

Methods

We stimulated infralimbic cortex (IL), the rat analog of sgACC, and recorded local electrical responses in amygdala (AMG) that is monosynaptically connected to IL and plays a central role in emotional states. We further traced AMG–IL connections using a viral vector and tractography using diffusion magnetic resonance imaging (MRI). Finally, we mimicked the clinical situation by delivering sustained 130 Hz stimulation at IL at the most effective field orientation and followed changes in resting-state functional connectivity with IL using functional MRI. To help interpretation of responses in functional connectivity, we stimulated only the left IL, which we did not expect to evoke measurable changes in the rat behavior.

Results

The AMG evoked responses depended systematically on the IL stimulation field orientation and yielded the maximum response in near vertical field orientation in accordance with tractography. Sustained 130 Hz stimulation at a field orientation yielding the strongest AMG evoked responses increased functional connectivity between IL and AMG on the stimulation side.

Conclusion

These findings suggest that OSS in 3D provides a new approach to optimize the DBS for every individual patient with a single stimulation probe implantation.
Developmental ethanol exposure has minimal impact on cerebellar microglial dynamics, morphology, and interactions with Purkinje cells during adolescence
Authors: Cealie MaKenna Y. , Douglas James C. , Le Linh H. D. , Vonkaenel Erik D. , McCall Matthew N. , Drew Paul D. , Majewska Ania K.
Published: May 2023

Introduction

Fetal alcohol spectrum disorders (FASD) are the most common cause of non-heritable, preventable mental disability, occurring in almost 5% of births in the United States. FASD lead to physical, behavioral, and cognitive impairments, including deficits related to the cerebellum. There is no known cure for FASD and their mechanisms remain poorly understood. To better understand these mechanisms, we examined the cerebellum on a cellular level by studying microglia, the principal immune cells of the central nervous system, and Purkinje cells, the sole output of the cerebellum. Both cell types have been shown to be affected in models of FASD, with increased cell death, immune activation of microglia, and altered firing in Purkinje cells. While ethanol administered in adulthood can acutely depress the dynamics of the microglial process arbor, it is unknown how developmental ethanol exposure impacts microglia dynamics and their interactions with Purkinje cells in the long term.

Methods

To address this question, we used a mouse model of human 3rd trimester exposure, whereby L7cre/Ai9+/−/Cx3cr1G/+ mice (with fluorescently labeled microglia and Purkinje cells) of both sexes were subcutaneously treated with a binge-level dose of ethanol (5.0 g/kg/day) or saline from postnatal days 4–9. Cranial windows were implanted in adolescent mice above the cerebellum to examine the long-term effects of developmental ethanol exposure on cerebellar microglia and Purkinje cell interactions using in vivo two-photon imaging.

Results

We found that cerebellar microglia dynamics and morphology were not affected after developmental ethanol exposure. Microglia dynamics were also largely unaltered with respect to how they interact with Purkinje cells, although subtle changes in these interactions were observed in females in the molecular layer of the cerebellum.

Discussion

This work suggests that there are limited in vivo long-term effects of ethanol exposure on microglia morphology, dynamics, and neuronal interactions, so other avenues of research may be important in elucidating the mechanisms of FASD.
Impact of zinc and iron agronomic biofortification on grain mineral concentration of finger millet varieties as affected by location and slope
Authors: Teklu Demeke , Gashu Dawd , Joy Edward J. M. , Lark R. Murray , Bailey Elizabeth H. , Wilson Lolita , Amede Tilahun , Broadley Martin R.
Published: May 2023

Background

Food crop micronutrient concentrations can be enhanced through agronomic biofortification, with the potential to reduce micronutrient deficiencies among rural population if they have access to fertilizers. Here we reported the impact of agronomic biofortification on finger millet grain zinc (Zn) and iron (Fe) concentration.

Methods

A field experiment was conducted in farmers’ fields in Ethiopia in two locations; over two seasons in one district (2019 and 2020), and over a single season (2019) in a second district. The experimental design had 15 treatment combinations comprising 3 finger millet varieties and 5 soil-applied fertilizer treatments: (T1) 20 kg ha−1 FeSO4 + 25 kg ha−1 ZnSO4 + NPKS; (T2) 25 kg ha−1 ZnSO4 + NPKS; (T3) NPKS; (T4) 30% NPKS; (T5) 20 kg ha−1 FeSO4 + NPKS. The treatments were studied at two slope positions (foot and hill), replicated four times in a randomized complete block design.

Results

Grain Zn concentration increased by 20% in response to Fe and Zn and by 18.9% due to Zn addition. Similarly, grain Fe concentration increased by 21.4% in T1 and 17.8% in T5 (Fe). Zinc fertilizer application (p < 0.001), finger millet variety (p < 0.001), and an interaction of Fe and Zn had significant effect on grain Zn concentration. Iron fertilizer (p < 0.001) and interactive effect of Fe fertilizer and finger millet variety (p < 0.01) had significant effects on grain Fe concentration. Location but not slope position was a source of variation for both grain Zn and Fe concentrations.

Conclusion

Soil application of Zn and Fe could be a viable strategy to enhance grain Zn and Fe concentration to finger millet grain. If increased grain Zn and Fe is bioavailable, it could help to combat micronutrient deficiencies.
The influence of conventional and novel blanching methods on potato granules, phytochemicals, and thermal properties of colored varieties
Authors: Saini Rajni , Kaur Sukhpreet , Aggarwal Poonam , Dhiman Atul
Published: May 2023

Introduction

Colored potatoes comprise many bioactive compounds that potentially support human health. Polyphenols present in them have associated therapeutic benefits like antimutagenic and anticarcinogenic properties.

Method

The current study aimed to explore the effects of different blanching methods (steam blanching, hot water blanching, and microwave-assisted blanching) on the phytochemical and structural aspects of PP-1901 and Lady Rosetta (LR) potato varieties. Changes in the antioxidant activity, color, total ascorbic acid, phenolic, and flavonoid content were based on the variations in parameters including temperature (blanching using hot water and steam) and capacity 100– 900 W (blanching using microwave).

Results

For both PP-1901 and LR varieties, all the blanching methods led to a significant reduction in residual peroxidase activity, as well as affecting their color. The preservation of bioactive substances exhibited a microwave steam>hot water blanching trend. Blanching significantly increased the antioxidant activity of all the samples. Additionally, Fourier-transform infrared spectroscopy revealed that phytocompounds were retained to their maximum in microwave-blanched samples, especially at 300 W. The type of blanching method significantly affected the thermal properties of potatoes by disrupting the ordered structure of the matrix.

Discussion

Microwaves at 300 W can be used as a novel and suitable alternative technique for blanching potatoes, which successfully retained the original quality of it in comparison to steam and hot water blanching.
Risk factors for early-onset colorectal cancer: systematic review and meta-analysis
Authors: Hua Hongmei , Jiang Qiuping , Sun Pan , Xu Xing
Published: May 2023

Background

The incidence of early-onset colorectal cancer (EOCRC), which means colorectal cancer diagnosed in patients under 50 years, has been increasing around the world. However, the etiology remains unclear. This study aims to identify risk factors for EOCRC.

Methods

This systematic review was conducted in PubMed, Embase, Scopus, and Cochrane Library databases from inception to November 25, 2022. We examined risk factors for EOCRC, including demographic factors, chronic conditions, and lifestyle behaviors or environmental factors. Random-effects/fixed-effects meta-analysis was adopted to combine effect estimates from published data. Study quality was evaluated with the Newcastle-Ottawa Scale (NOS). Statistical analysis was performed Revman5.3. Studies not suitable for the meta-analysis were analyzed by a systematic review.

Results

A total of 36 studies were identified for this review, and 30 studies were included in the meta-analysis. Significant risk factors for EOCRC included male (OR=1.20; 95% CI, 1.08-1.33), Caucasian (OR=1.44; 95% CI, 1.15-1.80), a family history of CRC (OR=5.90; 95% CI, 3.67-9.48), inflammatory bowel disease (OR=4.43; 95% CI, 4.05-4.84), obesity (OR=1.52; 95%CI, 1.20-1.91), overweight (OR=1.18; 95% CI, 1.12-1.25), triglycerides (OR=1.12; 95% CI, 1, 08-1.18), hypertension (OR=1.16; 95% CI, 1.12-1.21), metabolic syndrome (OR=1.29; 95% CI, 1.15-1.45), smoking (OR=1.44; 95% CI, 1.10-1.88), alcohol consumption (OR=1.41; 95% CI, 1.22-1.62), a sedentary lifestyle (OR=1.24; 95% CI, 1.05-1.46), red meat (OR=1.10; 95% CI, 1.04-1.16), processed meat (OR=1.53; 95% CI, 1.13-2.06), Western dietary patterns (OR=1.43; 95% CI, 1.18-1.73) and sugar-sweetened beverages (OR=1.55; 95% CI, 1.23-1.95). However, no statistical differences were found for hyperlipidemia and hyperglycemia. Vitamin D may be a protective factor (OR=0.72; 95% CI, 0.56-0.92). There was considerable heterogeneity among studies (I2>60%).

Conclusions

The study provides an overview of the etiology and risk factors of EOCRC. Current evidence can provide baseline data for risk prediction models specific to EOCRC and risk-tailored screening strategies.
Machine learning models combining computed tomography semantic features and selected clinical variables for accurate prediction of the pathological grade of bladder cancer
Authors: Deng Zhikang , Dong Wentao , Xiong Situ , Jin Di , Zhou Hongzhang , Zhang Ling , Xie LiHan , Deng Yaohong , Xu Rong , Fan Bing
Published: May 2023

Objective

The purpose of this research was to develop a radiomics model that combines several clinical features for preoperative prediction of the pathological grade of bladder cancer (BCa) using non-enhanced computed tomography (NE-CT) scanning images.

Materials and methods

The computed tomography (CT), clinical, and pathological data of 105 BCa patients attending our hospital between January 2017 and August 2022 were retrospectively evaluated. The study cohort comprised 44 low-grade BCa and 61 high-grade BCa patients. The subjects were randomly divided into training (n = 73) and validation (n = 32) cohorts at a ratio of 7:3. Radiomic features were extracted from NE-CT images. A total of 15 representative features were screened using the least absolute shrinkage and selection operator (LASSO) algorithm. Based on these characteristics, six models for predicting BCa pathological grade, including support vector machine (SVM), k-nearest neighbor (KNN), gradient boosting decision tree (GBDT), logical regression (LR), random forest (RF), and extreme gradient boosting (XGBOOST) were constructed. The model combining radiomics score and clinical factors was further constructed. The predictive performance of the models was evaluated based on the area under the receiver operating characteristic (ROC) curve, DeLong test, and decision curve analysis (DCA).

Results

The selected clinical factors for the model included age and tumor size. LASSO regression analysis identified 15 features most linked to BCa grade, which were included in the machine learning model. The SVM analysis revealed that the highest AUC of the model was 0.842. A nomogram combining the radiomics signature and selected clinical variables showed accurate prediction of the pathological grade of BCa preoperatively. The AUC of the training cohort was 0.919, whereas that of the validation cohort was 0.854. The clinical value of the combined radiomics nomogram was validated using calibration curve and DCA.

Conclusion

Machine learning models combining CT semantic features and the selected clinical variables can accurately predict the pathological grade of BCa, offering a non-invasive and accurate approach for predicting the pathological grade of BCa preoperatively.
Clinical application of indocyanine green fluorescence imaging navigation for pediatric renal cancer
Authors: Feng Jun , Yang Wei , Qin Hong , Xu Jiatong , Liu Shan , Han Jianyu , Li Ning , He Lejian , Wang Huanmin
Published: May 2023

Background

Indocyanine Green (ICG) fluorescence imaging has been widely used in the surgical treatment of adult renal cancers, but its application in pediatric renal cancers has rarely been reported. This study aims to summarize the experience of ICG fluorescence imaging in pediatric renal cancers and explores its safety and feasibility.

Methods

The clinical features, surgical information, ICG administration regimen, near infrared radiography data in vivo and ex vivo and pathological results of children with renal cancers using ICG navigation were analyzed and summarized.

Results

There were 7 cases of renal cancer, including 4 cases of Wilms tumor (WT), 1 case of malignant rhabdoid tumor of the kidney (MRTK) and 2 cases of renal cell carcinoma (RCC). By intraoperative intravenous injection of ICG from 2.5 to 5 mg (0.05–0.67 mg/kg), the tumors were visualized in 6 cases in vivo or ex vivo, and the tumor visualization failed in 1 case due to renal artery embolization before operation. By injecting 5 mg ICG into the normal renal tissue during the operation, 3 patients achieved fluorescent localization of sentinel lymph nodes. No ICG-related adverse reactions were found in any of the patients during or after operation.

Conclusions

ICG fluorescence imaging is safe and feasible for renal cancers in children. Intraoperative administration can achieve tumor and sentinel lymph node visualization which will facilitate the development of nephron sparing surgery (NSS). However, the technique is affected by ICG dose, anatomical conditions around the tumor, and renal blood flow. A proper dose of ICG and the complete removal of perirenal fat are helpful for the fluorescence imaging of the tumor. It has potential in the operation of renal cancer in children.
Curtailing virus-induced inflammation in respiratory infections: emerging strategies for therapeutic interventions
Authors: Globenko Alexander A. , Kuzin Gennady V. , Rydlovskaya Anastasia V. , Isaeva Elena I. , Vetrova Elizaveta N. , Pritchina Tat’yana N. , Baranova Ancha , Nebolsin Vladimir E.
Published: May 2023

Acute respiratory viral infections (ARVI) are the most common illnesses worldwide. In some instances, mild cases of ARVI progress to hyperinflammatory responses, which are damaging to pulmonary tissue and requiring intensive care. Here we summarize available information on preclinical and clinical effects of XC221GI (1-[2-(1-methyl imidazole-4-yl)-ethyl]perhydroazin-2,6-dione), an oral drug with a favorable safety profile that has been tested in animal models of influenza, respiratory syncytial virus, highly pathogenic coronavirus strains and other acute viral upper respiratory infections. XC221GI is capable of controlling IFN-gamma-driven inflammation as it is evident from the suppression of the production of soluble cytokines and chemokines, including IL-6, IL-8, CXCL10, CXCL9 and CXCL11 as well as a decrease in migration of neutrophils into the pulmonary tissue. An excellent safety profile of XC221GI, which is not metabolized by the liver, and its significant anti-inflammatory effects indicate utility of this compound in abating conversion of ambulatory cases of respiratory infections into the cases with aggravated presentation that require hospitalization. This drug is especially useful when rapid molecular assays determining viral species are impractical, or when direct antiviral drugs are not available. Moreover, XC221GI may be combined with direct antiviral drugs to enhance their therapeutic effects.
Hydroxychloroquine and azithromycin alter the contractility of living porcine heart slices
Authors: Wu Qin , Ross Abigail J. , Ipek Tugce , Thompson Georgina H. , Johnson Robert D. , Wu Changhao , Camelliti Patrizia
Published: May 2023

The cardiotoxicity risk of hydroxychloroquine (HCQ) and azithromycin (AZM) has been the subject of intensive research triggered by safety concerns in COVID-19 patients. HCQ and AZM have been associated with QT interval prolongation and drug-induced arrhythmias, however other cardiotoxicity mechanisms remain largely unexplored. Our group has pioneered the living heart slice preparation, an ex-vivo platform that maintains native cardiac tissue architecture and physiological electrical and contractile properties. Here, we evaluated the cardiotoxic effect of HCQ and AZM applied alone or in combination on cardiac contractility by measuring contractile force and contraction kinetics in heart slices prepared from porcine hearts. Our results show that clinically relevant concentrations of HCQ monotherapy (1–10 µM) reduced contractile force and contraction kinetics in porcine slices in a dose-dependent manner. However, AZM monotherapy decreased contractile force and contraction kinetics only at higher concentrations (30 µM). Combination of HCQ and AZM induced a dose-dependent effect similar to HCQ alone. Furthermore, pre-treating porcine heart slices with the L-type calcium channel agonist Bay K8644 prevented the effect of both drugs, while administration of Bay K8644 after drugs interventions largely reversed the effects, suggesting a mechanism involving inhibition of L-type calcium channels. These findings indicate that HCQ and AZM alter cardiac function beyond QT prolongation with significant contractile dysfunction in intact cardiac tissue. Our porcine heart slices provide a powerful platform to investigate mechanisms of drug cardiotoxicity.
Sacubitril/valsartan: research progress of multi-channel therapy for cardiorenal syndrome
Authors: Wang Shuangcui , Wang Yuli , Deng Yun , Zhang Jiaqi , Jiang Xijuan , Yu Jianchun , Gan Jiali , Zeng Wenyun , Guo Maojuan
Published: May 2023

Cardiorenal syndrome (CRS) results from complex interaction between heart and kidneys, inducing simultaneous acute or chronic dysfunction of these organs. Although its incidence rate is increasing with higher mortality in patients, effective clinical treatment drugs are currently not available. The literature suggests that renin-angiotensin-aldosterone system (RAAS) and diuretic natriuretic peptide (NP) system run through CRS. Drugs only targeting the RAAS and NPs systems are not effective. Sacubitril/valsartan contains two agents (sacubitril and valsartan) that can regulate RAAS and NPs simultaneously. In the 2017 American College of Cardiology/American Heart Association/American Heart Failure (HF) ssociation (ACC/AHA/HFSA) guideline, sacubitril/valsartan was recommended as standard therapy for HF patients. The latest research shows that Combined levosimendan and Sacubitril/Valsartan markets are protected the heart and kidney against cardiovascular syndrome in rat. However, fewer studies have reported its therapeutic efficacy in CRS treatment, and their results are inconclusive. Therefore, based on RAAS and NPs as CRS biomarkers, this paper summarizes possible pathophysiological mechanisms and preliminary clinical application effects of sacubitril/valsartan in the prevention and treatment of CRS. This will provide a pharmacological justification for expanding sacubitril/valsartan use to the treatment of CRS.
Examining the paradoxical effects of kratom: a narrative inquiry
Authors: Smith Kirsten E. , Feldman Jeffrey D. , Dunn Kelly E. , McCurdy Christopher R. , Weiss Stephanie T. , Grundmann Oliver , Garcia-Romeu Albert , Nichels Janeen , Epstein David H.
Published: May 2023

Introduction: Surveys and case reports have documented kratom use in the United States (US) for over a decade. However, those reports have generally not examined in depth the role kratom plays in the lives of those who use it regularly for sustained periods. Until there are controlled studies of the pharmacology and subjective effects of kratom alkaloids in humans, one of the best sources of insight on kratom-product use remains qualitative data with nuanced descriptions of kratom effects from those who use it regularly.

Method: We conducted semistructured qualitative interviews with adults who regularly use kratom products, as part of a laboratory study of kratom-product self-administration. This qualitative component of the study was conducted as a narrative case-report series (n = 10).

Results: Despite some differences among participants, all experienced acute combination effects that were largely, even simultaneously, analgesic and stimulatory. Most participants had decreased their dosages over time, and one planned to quit. Five of the 10 participants met DSM-5-based criteria for kratom-use disorder (3 mild, 1 moderate, 1 severe, by symptoms counts). When kratom was inadvertently taken in larger than intended doses, participants described a constellation of symptoms that they called “the wobbles” (a jittery feeling accompanied by what seemed to be nystagmus); this was rare, but could be of scientific and clinical interest as a possible manifestation of serotonin syndrome. Most participants described tolerance but considered kratom generally safe at low-moderate doses, providing perceived benefits with less potential risk for adverse effects compared to pharmaceuticals or illicit drugs.

Discussion: In-depth interview data like these help confirm and clarify findings from larger survey studies and clinician-driven case reports. They are needed to inform the policy practice regarding kratom and may also help inform future experimental designs.
Effects of early adjunctive pharmacotherapy on serum levels of brain injury biomarkers in patients with traumatic brain injury: a systematic review of randomized controlled studies
Authors: Mansour Noha O. , Elnaem Mohamed Hassan , Abdelaziz Doaa H. , Barakat Muna , Dehele Inderpal Singh , Elrggal Mahmoud E. , Abdallah Mahmoud S.
Published: May 2023

Objectives: Traumatic brain injury (TBI) is one of the top causes of morbidity and mortality worldwide. The review aimed to discuss and summarize the current evidence on the effectiveness of adjuvant neuroprotective treatments in terms of their effect on brain injury biomarkers in TBI patients.

Methods: To identify relevant studies, four scholarly databases, including PubMed, Cochrane, Scopus, and Google Scholar, were systematically searched using predefined search terms. English-language randomized controlled clinical trials reporting changes in brain injury biomarkers, namely, neuron-specific enolase (NSE), glial fibrillary acid protein (GFAP), ubiquitin carboxyl-terminal esterase L1 (UCHL1) and/or S100 beta (S100 ß), were included. The methodological quality of the included studies was assessed using the Cochrane risk-of-bias tool.

Results: A total of eleven studies with eight different therapeutic options were investigated; of them, tetracyclines, metformin, and memantine were discovered to be promising choices that could improve neurological outcomes in TBI patients. The most utilized serum biomarkers were NSE and S100 ß followed by GFAP, while none of the included studies quantified UCHL1. The heterogeneity in injury severity categories and measurement timing may affect the overall evaluation of the clinical efficacy of potential therapies. Therefore, unified measurement protocols are highly warranted to inform clinical decisions.

Conclusion: Few therapeutic options showed promising results as an adjuvant to standard care in patients with TBI. Several considerations for future work must be directed towards standardizing monitoring biomarkers. Investigating the pharmacotherapy effectiveness using a multimodal biomarker panel is needed. Finally, employing stratified randomization in future clinical trials concerning potential confounders, including age, trauma severity levels, and type, is crucial to inform clinical decisions.

Clinical Trial Registration: [https://www.crd.york.ac.uk/prospero/dis], identifier [CRD42022316327].
Dynamical behaviors of an epidemic model for malware propagation in wireless sensor networks
Authors: Zhou Ying , Wang Yan , Zhou Kai , Shen Shou-Feng , Ma Wen-Xiu
Published: May 2023

To explore malware propagation mechanisms in networks and to develop optimal strategies for controlling the spread of malware, we propose a susceptible-unexposed-infected-isolation-removed epidemic model. First, we establish a non-linear dynamic equation of malware propagation. Then, the basic reproductive number is derived by using the next-generation method. Finally, we carry out numerical simulations to observe the malware spreading in WSNs to verify the obtained theoretical results. Furthermore, we investigate the communication range of the nodes to make the results more complete. The optimal range of the nodes is designed to control malware propagation.
Allosteric modulators of solute carrier function: a theoretical framework
Authors: Boytsov D. , Schicker K. , Hellsberg E. , Freissmuth M. , Sandtner W.
Published: May 2023

Large-scale drug screening is currently the basis for the identification of new chemical entities. This is a rather laborious approach, because a large number of compounds must be tested to cover the chemical space in an unbiased fashion. However, the structures of targetable proteins have become increasingly available. Thus, a new era has arguably been ushered in with the advent of methods, which allow for structure-based docking campaigns (i.e., virtual screens). Solute carriers (SLCs) are among the most promising drug targets. This claim is substantiated by the fact that a large fraction of the 400 solute carrier genes is associated with human diseases. The ability to dock large ligand libraries into selected structures of solute carriers has set the stage for rational drug design. In the present study, we show that these structure-based approaches can be refined by taking into account how solute carriers operate. We specifically address the feasibility of targeting solute carriers with allosteric modulators, because their actions differ fundamentally from those of ligands, which bind to the substrate binding site. For the pertinent analysis we used transition state theory in conjunction with the linear free energy relationship (LFER). These provide the theoretical framework to understand how allosteric modulators affect solute carrier function.
Detecting different pesticide residues on Hami melon surface using hyperspectral imaging combined with 1D-CNN and information fusion
Authors: Hu Yating , Ma Benxue , Wang Huting , Zhang Yuanjia , Li Yujie , Yu Guowei
Published: May 2023

Efficient, rapid, and non-destructive detection of pesticide residues in fruits and vegetables is essential for food safety. The visible/near infrared (VNIR) and short-wave infrared (SWIR) hyperspectral imaging (HSI) systems were used to detect different types of pesticide residues on the surface of Hami melon. Taking four pesticides commonly used in Hami melon as the object, the effectiveness of single-band spectral range and information fusion in the classification of different pesticides was compared. The results showed that the classification effect of pesticide residues was better by using the spectral range after information fusion. Then, a custom multi-branch one-dimensional convolutional neural network (1D-CNN) model with the attention mechanism was proposed and compared with the traditional machine learning classification model K-nearest neighbor (KNN) algorithm and random forest (RF). The traditional machine learning classification model accuracy of both models was over 80.00%. However, the classification results using the proposed 1D-CNN were more satisfactory. After the full spectrum data was fused, it was input into the 1D-CNN model, and its accuracy, precision, recall, and F1-score value were 94.00%, 94.06%, 94.00%, and 0.9396, respectively. This study showed that both VNIR and SWIR hyperspectral imaging combined with a classification model could non-destructively detect different pesticide residues on the surface of Hami melon. The classification result using the SWIR spectrum was better than that using the VNIR spectrum, and the classification result using the information fusion spectrum was better than that using SWIR. This study can provide a valuable reference for the non-destructive detection of pesticide residues on the surface of other large, thick-skinned fruits.
Classification and localization of maize leaf spot disease based on weakly supervised learning
Authors: Yang Shuai , Xing Ziyao , Wang Hengbin , Gao Xiang , Dong Xinrui , Yao Yu , Zhang Runda , Zhang Xiaodong , Li Shaoming , Zhao Yuanyuan , Liu Zhe
Published: May 2023

Precisely discerning disease types and vulnerable areas is crucial in implementing effective monitoring of crop production. This forms the basis for generating targeted plant protection recommendations and automatic, precise applications. In this study, we constructed a dataset comprising six types of field maize leaf images and developed a framework for classifying and localizing maize leaf diseases. Our approach involved integrating lightweight convolutional neural networks with interpretable AI algorithms, which resulted in high classification accuracy and fast detection speeds. To evaluate the performance of our framework, we tested the mean Intersection over Union (mIoU) of localized disease spot coverage and actual disease spot coverage when relying solely on image-level annotations. The results showed that our framework achieved a mIoU of up to 55.302%, indicating the feasibility of using weakly supervised semantic segmentation based on class activation mapping techniques for identifying disease spots in crop disease detection. This approach, which combines deep learning models with visualization techniques, improves the interpretability of the deep learning models and achieves successful localization of infected areas of maize leaves through weakly supervised learning. The framework allows for smart monitoring of crop diseases and plant protection operations using mobile phones, smart farm machines, and other devices. Furthermore, it offers a reference for deep learning research on crop diseases.
Comprehensive analysis of HSF genes from celery (Apium graveolens L.) and functional characterization of AgHSFa6-1 in response to heat stress
Authors: Li Mengyao , Zhang Ran , Zhou Jin , Du Jiageng , Li Xiaoyan , Zhang Yong , Chen Qing , Wang Yan , Lin Yuanxiu , Zhang Yunting , He Wen , Wang Xiaorong , Xiong Aisheng , Luo Ya , Tang Haoru
Published: May 2023

High temperature stress is regarded as one of the significant abiotic stresses affecting the composition and distribution of natural habitats and the productivity of agriculturally significant plants worldwide. The HSF family is one of the most important transcription factors (TFs) families in plants and capable of responding rapidly to heat and other abiotic stresses. In this study, 29 AgHSFs were identified in celery and classified into three classes (A, B, and C) and 14 subgroups. The gene structures of AgHSFs in same subgroups were conserved, whereas in different classes were varied. AgHSF proteins were predicted to be involved in multiple biological processes by interacting with other proteins. Expression analysis revealed that AgHSF genes play a significant role in response to heat stress. Subsequently, AgHSFa6-1, which was significantly induced by high temperature, was selected for functional validation. AgHSFa6-1 was identified as a nuclear protein, and can upregulate the expression of certain downstream genes (HSP98.7, HSP70-1, BOB1, CPN60B, ADH2, APX1, GOLS1) in response to high-temperature treatment. Overexpression of AgHSFa6-1 in yeast and Arabidopsis displayed higher thermotolerance, both morphologically and physiologically. In response to heat stress, the transgenic plants produced considerably more proline, solute protein, antioxidant enzymes, and less MDA than wild-type (WT) plants. Overall, this study revealed that AgHSF family members perform a key role in response to high temperature, and AgHSFa6-1 acts as a positive regulator by augmenting the ROS-scavenging system to maintain membrane integrity, reducing stomatal apertures to control water loss, and upregulating the expression level of heat-stress sensitive genes to improve celery thermotolerance.
Mesophyll conductance and N allocation co-explained the variation in photosynthesis in two canola genotypes under contrasting nitrogen supply
Authors: Liu Jiahuan , Zhang Kangkang , Bi Junguo , Yu Xinqiao , Luo Lijun , Hu Liyong
Published: May 2023

The application of nitrogen fertilizer within a normal range has been found to increase the leaf nitrogen content and photosynthetic rate of canola plants (Brassica napus L.). Despite numerous studies on the separate effects of CO2 diffusion limitation and nitrogen allocation trade-off on photosynthetic rate, few have examined both these factors in relation to the photosynthetic rate of canola. In this study, two genotypes of canola with varying leaf nitrogen content were analyzed to determine the impact of nitrogen supply on leaf photosynthesis, mesophyll conductance, and nitrogen partitioning. The results showed that the CO2 assimilation rate (A), mesophyll conductance (gm), and photosynthetic nitrogen content (Npsn) increased with an increase in nitrogen supply in both genotypes. The relationship between nitrogen content and A followed a linear-plateau regression, while A had linear relationships with both photosynthetic nitrogen content and gm, indicating that the key to enhancing A is increasing the distribution of leaf nitrogen into the photosynthetic apparatus and gm, rather than just increasing nitrogen content. Under high nitrogen treatment, the genotype (QZ) with high nitrogen content had 50.7% more nitrogen than the other genotype (ZY21), but had similar A, which was primarily due to ZY21’s higher photosynthetic nitrogen distribution ratio and stomatal conductance (gsw). On the other hand, QZ showed a higher A than ZY21 under low nitrogen treatment as QZ had higher Npsn and gm compared to ZY21. Our results indicate that, in selecting high PNUE rapeseed varieties, it is important to consider the higher photosynthetic nitrogen distribution ratio and CO2 diffusion conductance.
Drought-triggered leaf transcriptional responses disclose key molecular pathways underlying leaf water use efficiency in sugarcane (Saccharum spp.)
Authors: Contiliani Danyel F. , Nebó João Felipe C. de O. , Ribeiro Rafael V. , Landell Marcos G. de A. , Pereira Tiago C. , Ming Ray , Figueira Antonio , Creste Silvana
Published: May 2023

Drought is a major constraint to sugarcane (Saccharum spp.) production and improving the water use efficiency (WUE) is a critical trait for the sustainability of this bioenergy crop. The molecular mechanism underlying WUE remains underexplored in sugarcane. Here, we investigated the drought-triggered physiological and transcriptional responses of two sugarcane cultivars contrasting for drought tolerance, ‘IACSP97-7065’ (sensitive) and ‘IACSP94-2094’ (tolerant). After 21 days without irrigation (DWI), only ‘IACSP94-2094’ exhibited superior WUE and instantaneous carboxylation efficiency, with the net CO2 assimilation being less impacted when compared with ‘IACSP97-7065’. RNA-seq of sugarcane leaves at 21 DWI revealed a total of 1,585 differentially expressed genes (DEGs) for both genotypes, among which ‘IACSP94-2094’ showed 617 (38.9%) exclusive transcripts (212 up- and 405 down-regulated). Functional enrichment analyses of these unique DEGs revealed several relevant biological processes, such as photosynthesis, transcription factors, signal transduction, solute transport, and redox homeostasis. The better drought-responsiveness of ‘IACSP94-2094’ suggested signaling cascades that foster transcriptional regulation of genes implicated in the Calvin cycle and transport of water and carbon dioxide, which are expected to support the high WUE and carboxylation efficiency observed for this genotype under water deficit. Moreover, the robust antioxidant system of the drought-tolerant genotype might serve as a molecular shield against the drought-associated overproduction of reactive oxygen species. This study provides relevant data that may be used to develop novel strategies for sugarcane breeding programs and to understand the genetic basis of drought tolerance and WUE improvement of sugarcane.
Genome-wide characterization of ascorbate peroxidase gene family in pepper (Capsicum annuum L.) in response to multiple abiotic stresses
Authors: Pang Xin , Chen Jun , Xu Yang , Liu Jia , Zhong Yangmin , Wang Linlin , Zheng Jiaqiu , Wan Hongjian
Published: May 2023

Pepper is widely grown all over the world, so it faces many abiotic stresses, such as drought, high temperature, low temperature, salt damage, and so on. Stresses causing the accumulation of reactive oxidative species (ROS) in plants are removed by antioxidant defense systems, and ascorbate peroxidase (APX) is an important antioxidant enzyme. Therefore, the present study performed genome-wide identification of the APX gene family in pepper. We identified nine members of the APX gene family in the pepper genome according to the APX proteins’ conserved domain in Arabidopsis thaliana. The physicochemical property analysis showed that CaAPX3 had the longest protein sequence and the largest molecular weight of all genes, while CaAPX9 had the shortest protein sequence and the smallest MW. The gene structure analysis showed that CaAPXs were composed of seven to 10 introns. The CaAPX genes were divided into four groups. The APX genes of groups I and IV were localized in the peroxisomes and chloroplasts, respectively; the group II genes were localized in the chloroplasts and mitochondria; and the group III genes were located in the cytoplasm and extracell. The conservative motif analysis showed that all APX genes in the pepper had motif 2, motif 3, and motif 5. The APX gene family members were distributed on five chromosomes (Chr. 2, 4, 6, 8, and 9). The cis-acting element analysis showed that most CaAPX genes contain a variety of cis-elements related to plant hormones and abiotic stress. RNA-seq expression analysis showed that the expression patterns of nine APXs were different in vegetative and reproductive organs at different growth and development stages. In addition, the qRT-PCR analysis of the CaAPX genes revealed significant differential expression in response to high temperature, low temperature, and salinity stresses in leaf tissue. In conclusion, our study identified the APX gene family members in the pepper and predicted the functions of this gene family, which would provide resources for further functional characterization of CaAPX genes.
Glucagon-like peptide-1 receptor-agonists treatment for cardio-metabolic parameters in schizophrenia patients: a systematic review and meta-analysis
Authors: Khaity Abdulrhman , Mostafa Al-dardery Nada , Albakri Khaled , Abdelwahab Omar A. , Hefnawy Mahmoud Tarek , Yousef Yaman A. S. , Taha Ruaa E. , Swed Sarya , Hafez Wael , Hurlemann Rene , Elsayed Mohamed E. G.
Published: May 2023

Aims

We performed this meta-analysis to evaluate the efficacy and safety of glucagon-like peptide-1 receptor-agonists (GLP-1RA) treatment on cardio-metabolic parameters among antipsychotic-treated patients with schizophrenia.

Methods

We searched the Web of Science, Cochrane Central Register of Controlled Trials, PubMed, PsycINFO, and Scopus for relevant Randomized Clinical trials (RCTs) from inception until 1 August 2022. Documents were screened for qualified articles, and all concerned outcomes were pooled as risk ratios (RR) or mean difference (MD) in the meta-analysis models using Review Manager (RevMan version 5.4).

Results

Pooling data from 7 RCTs (398 patients) showed that GLP-1 RA was superior to placebo with regard to body weight [MD = - 4.68, 95% CI (-4.90,−4.46), P < 0.00001], waist circumference [MD = - 3.66, 95% CI (-3.89,−3.44), P < 0.00001], body mass index (BMI) [MD = - 1.09, 95% CI (-1.25,−0.93), P < 0.00001], systolic blood pressure (SBP) [MD = - 3.07, 95% CI (-3.61,−2.53), P < 0.00001], and diastolic blood pressure (DBP) [MD = - 2.02, 95% CI (-2.42,−1.62), P < 0.00001]. The total effect did not favor either of the two groups with respect to insulin and respiratory adverse events {[MD = - 0.06, 95% CI (-0.36, 0.24), p = 0.70], [RR = 0.66, 95% CI (0.31, 1.40), p = 0.28]; respectively}.

Conclusion

Our analysis revealed that GLP-1 RA treatment is safe and effective on cardio-metabolic parameters over control in antipsychotic-treated patients with schizophrenia. Nevertheless, the present evidence is not sufficient to confirm the safety and efficacy of GLP-1RA treatment on insulin and respiratory adverse events. Therefore, further studies are recommended.

Systematic review registration

http://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022333040.