bluuebunny/crossref_metadata_2025 huggingface dataset:
Lateral Habenula Beyond Avoidance: Roles in Stress, Memory, and Decision-Making With Implications for Psychiatric Disorders
Authors: Baker Phillip M. , Mathis Victor , Lecourtier Lucas , Simmons Sarah C. , Nugent Fereshteh S. , Hill Sierra , Mizumori Sheri J. Y.
Published: March 2022

In this Perspective review, we highlight some of the less explored aspects of lateral habenula (LHb) function in contextual memory, sleep, and behavioral flexibility. We provide evidence that LHb is well-situated to integrate different internal state and multimodal sensory information from memory-, stress-, motivational-, and reward-related circuits essential for both survival and decision making. We further discuss the impact of early life stress (ELS) on LHb function as an example of stress-induced hyperactivity and dysregulation of neuromodulatory systems within the LHb that promote anhedonia and motivational deficits following ELS. We acknowledge that recent technological advancements in manipulation and recording of neural circuits in simplified and well-controlled behavioral paradigms have been invaluable in our understanding of the critical role of LHb in motivation and emotional regulation as well as the involvement of LHb dysfunction in stress-induced psychopathology. However, we also argue that the use of ethologically-relevant behaviors with consideration of complex aspects of decision-making is warranted for future studies of LHb contributions in a wide range of psychiatric illnesses. We conclude this Perspective with some of the outstanding issues for the field to consider where a multi-systems approach is needed to investigate the complex nature of LHb circuitry interactions with environmental stimuli that predisposes psychiatric disorders.
Normal Variants and Pitfalls of 18F-FDG PET/CT Imaging in Pediatric Oncology
Authors: Purbhoo Khushica , Vangu Mboyo Di-Tamba
Published: March 2022

Positron emission tomography (PET) with 2-[fluorine-18] fluoro-2- deoxy-D-glucose (FDG) is a well-established modality that is used in adult oncologic imaging. Its use in pediatric oncology has increased over time. It enables increased diagnostic accuracy due to the combination of functional and morphologic imaging, resulting in optimal patient management. However, the clinician should be aware that the normal distribution of FDG uptake in children differs from adults. Also, even though FDG is used widely in oncology, it is not tumor specific. Uptake of FDG may be seen in numerous benign conditions, including inflammation, infection, and trauma. Proper interpretation of pediatric FDG PET/CT studies requires knowledge of the normal distribution of FDG uptake in children, and an insight into the physiologic variants, benign lesions, and PET/CT related artifacts. Understanding the potential causes of misinterpretation increases the confidence of image interpretation, reduce the number of unnecessary follow-up studies, optimize treatment and more importantly, reduce the radiation exposure to the patient. We review and discuss the physiological distribution of FDG uptake in children, the variation in distribution, lesions that are benign that could be misinterpreted as malignancy, and the various artifacts associated with PET/CT performed in pediatric oncology patients. We add a pictorial illustration to prompt understanding and familiarity of the above-mentioned patterns. Therefore, we believe that this review will assist in reducing possible mistakes by reading physicians and prevent incorrect interpretation.
Immune Checkpoint Inhibitor-Induced Central Diabetes Insipidus: Looking for the Needle in the Haystack or a Very Rare Side-Effect to Promptly Diagnose?
Authors: Barnabei Agnese , Strigari Lidia , Corsello Andrea , Paragliola Rosa Maria , Falzone Luca , Salvatori Roberto , Corsello Salvatore Maria , Torino Francesco
Published: March 2022

Immune checkpoint inhibitors have improved the survival in patients affected by an increasing number of malignancies, but they may also trigger various autoimmune side-effects, including endocrinopathies. Very rarely, immune checkpoint inhibitors have been reported to cause central diabetes insipidus. However, with their expanding use, the likelihood that oncologists will face this endocrine adverse event is expected to increase. By reviewing the limited literature on central diabetes insipidus induced by immune checkpoint inhibitors, some inconsistencies emerge in the diagnosis and the management of patients presenting with this toxicity, together with difficulties related to classifying its severity. Until now, specific guidelines on the management of central diabetes insipidus induced by immune checkpoint inhibitors are lacking. In clinical practice, endocrinological consultation may relieve medical oncologists from difficulties in treating this side-effect; oncologists, however, remain responsible for its early diagnose and the management of the causative drugs. To this aim, some practical suggestions are advised for the multidisciplinary management of cancer patients presenting with central diabetes insipidus induced by immune checkpoint inhibitors.
Accuracy Improvement Method Based on Characteristic Database Classification for IMRT Dose Prediction in Cervical Cancer: Scientifically Training Data Selection
Authors: Peng Yiru , Liu Yaoying , Chen Zhaocai , Zhang Gaolong , Ma Changsheng , Xu Shouping , Yin Yong
Published: March 2022

Purpose

Consistent training and testing datasets can lead to good performance for deep learning (DL) models. However, a large high-quality training dataset for unusual clinical scenarios is usually not easy to collect. The work aims to find optimal training data collection strategies for DL-based dose prediction models.

Materials and Methods

A total of 325 clinically approved cervical IMRT plans were utilized. We designed comparison experiments to investigate the impact of (1) beam angles, (2) the number of beams, and (3) patient position for DL dose prediction models. In addition, a novel geometry-based beam mask generation method was proposed to provide beam setting information in the model training process. What is more, we proposed a new training strategy named “full-database pre-trained strategy”.

Results

The model trained with a homogeneous dataset with the same beam settings achieved the best performance [mean prediction errors of planning target volume (PTV), bladder, and rectum: 0.29 ± 0.15%, 3.1 ± 2.55%, and 3.15 ± 1.69%] compared with that trained with large mixed beam setting plans (mean errors of PTV, bladder, and rectum: 0.8 ± 0.14%, 5.03 ± 2.2%, and 4.45 ± 1.4%). A homogeneous dataset is more accessible to train an accurate dose prediction model (mean errors of PTV, bladder and rectum: 2.2 ± 0.15%, 5 ± 2.1%, and 3.23 ± 1.53%) than a non-homogeneous one (mean errors of PTV, bladder and rectum: 2.55 ± 0.12%, 6.33 ± 2.46%, and 4.76 ± 2.91%) without other processing approaches. The added beam mask can constantly improve the model performance, especially for datasets with different beam settings (mean errors of PTV, bladder, and rectum improved from 0.8 ± 0.14%, 5.03 ± 2.2%, and 4.45 ± 1.4% to 0.29 ± 0.15%, 3.1 ± 2.55%, and 3.15 ± 1.69%).

Conclusions

A consistent dataset is recommended to form a patient-specific IMRT dose prediction model. When a consistent dataset is not accessible to collect, a large dataset with different beam angles and a training model with beam information can also get a relatively good model. The full-database pre-trained strategies can rapidly form an accuracy model from a pre-trained model. The proposed beam mask can effectively improve the model performance. Our study may be helpful for further dose prediction studies in terms of training strategies or database establishment.
Real-World First-Line Treatment Patterns and Outcomes in Hormone Receptor-Positive Advanced Breast Cancer Patients: A Multicenter, Retrospective Study in China
Authors: Chen Zhanhong , Ouyang Quchang , Wang Yongsheng , Wang Junsheng , Wang Haixue , Wu Xiaohong , Zhang Peili , Huang Jian , Zheng Yabing , Cao Wenming , Shao Xiying , Xie Ning , Tian Can , Liang Hao , Wang Cailing , Zhang Ying , Ren Dianquan , Wang Xiaojia
Published: March 2022

Background

Recent data on first-line treatment patterns administered to hormone receptor-positive (HR+) advanced breast cancer (ABC) patients in the real-world setting are limited. This study aimed to report the first-line treatment patterns and outcomes of HR+ ABC patients in China.

Methods

This was a multicenter, noninterventional study. Eligible patients were cytologically or histologically confirmed to have HR+ ABC with ≥2 complete medical records and received first-line therapies between January 2015 and June 2019. Treatment patterns and outcomes were extracted from structured or unstructured electronic medical records. Progression-free survival (PFS) was analyzed with the Kaplan-Meier method.

Results

In total, 1072 patients with HR+ ABC were enrolled at 6 treatment sites: 327 human epidermal growth factor receptor 2-positive (HER2+) patients, 696 HER2-negative (HER2-) patients and 49 HER2-unknown patients. Overall, 62.41% of patients received first-line chemotherapy (CT), 21.08% received targeted therapy (TT) and 15.49% received endocrine therapy (ET). For HR+/HER2+ patients, 65.14% received TT, 28.44% received CT, and 5.81% received ET. Compared with patients who received TT, patients who received CT alone, had a significantly worse median PFS (adjusted hazard ratio [HR] =2.59, 95% confidence interval [CI], 1.64-4.10, p<0.001). For HR+/HER2- patients, 77.01% received CT, 20.69% received ET and 1.15% received TT. Compared with patients who received ET, patients who received CT with maintenance therapy had a significantly prolonged median PFS (adjusted HR =0.57, 95% CI, 0.44-0.76, p<0.001). Among HR+/HER2- patients who received CT with maintenance treatment, those with maintenance ET had a longer median PFS than those with maintenance CT, but the difference was not significant (adjusted HR=0.92, 95% CI, 0.64-1.33, p=0.66).

Conclusions

This real-world study demonstrates that CT remains the mainstream first-line treatment option for HR+ patients in China. Among patients with HR+/HER2+ ABC, the majority received first-line TT and experienced a PFS benefit. A high percentage of HR+/HER2- patients received CT as first-line therapy in clinical practice. PFS benefit was significantly longer in patients who received CT with maintenance therapy. Moreover, there was no obvious difference in PFS between maintenance ET and CT. Maintenance ET may be a better choice considering its lower toxicity and better quality of life.
Effects of High-Frequency Oscillatory Ventilation With Volume Guarantee During Surfactant Treatment in Extremely Low Gestational Age Newborns With Respiratory Distress Syndrome: An Observational Study
Authors: Tana Milena , Paladini Angela , Tirone Chiara , Aurilia Claudia , Lio Alessandra , Bottoni Anthea , Costa Simonetta , Tiberi Eloisa , Pastorino Roberta , Vento Giovanni
Published: March 2022

Objective

To evaluate the effect of volume guarantee (VG) combined with high-frequency oscillatory ventilation (HFOV) on respiratory and other physiological parameters immediately after lung recruitment and surfactant administration in HFOV elective ventilated extremely low gestational age newborns (ELGAN) with respiratory distress syndrome (RDS).

Design

Observational study.

Setting

Tertiary neonatal intensive care unit.

Patients

Twenty-two ELGANs of 25.5 ± 1.1 weeks of gestational age requiring invasive mechanical ventilation and surfactant administration for RDS during the first 6 h of life.

Interventions

All infants intubated in delivery room, were managed with elective HFOV and received surfactant after a lung recruitment manoeuver. Eleven infants received HFOV + VG and were compared with a control group of 11 infants receiving HFOV alone. HFOV was delivered in both groups by Dräger Babylog VN500 ventilator (Dräger, Lubeck, Germany).

Main Outcome Measures

Variations and fluctuations of delivered high-frequency tidal volume (VThf), fluctuation of pressure amplitude (ΔP) and partial pressure of CO2 (pCO2) levels after recruitment manoeuver and immediately after surfactant administration, in HFOV + VG vs. HFOV ventilated infants.

Results

There were no significant differences in the two groups at starting ventilation with or without VG. The mean applied VThf per kg was 1.7 ± 0.3 ml/kg in the HFOV group and 1.7 ± 0.1 ml/kg in the HFOV + VG group. Thirty minutes after surfactant administration, HFOV group had a significant higher VThf/Kg than HFOV + VG (2.1 ± 0.3 vs. 1.6 ± 0.1 ml/kg, p < 0.0001) with significantly lower pCO2 levels (43.1 ± 3.8 vs. 46.8 ± 1.5 mmHg, p = 0.01), 54.4% of patients having pCO2 below 45 mmHg. Measured post-surfactant ΔP values were higher in HFOV group (17 ± 3 cmH2O) than in HFOV + VG group (13 ± 3 cmH2O, p = 0.01).

Conclusion

HFOV + VG maintains pCO2 levels within target range and reduces VThf delivered variations more consistently than HFOV alone after surfactant administration.
Interprofessional Teamwork to Promote Health: First-Time Parents' Experiences of a Combined Home Visit by Midwife and Child Health Care Nurse
Authors: Sjögren Forss Katarina , Mangrio Elisabeth , Hellström Lisa
Published: March 2022

Background

To achieve the requisites for a child's healthy development and to reduce health inequalities, it is important to promote health initiatives at an early stage in a child's life and to include the parents. Home visits by healthcare professionals have been found to have positive health effects for both the baby and the parents. From an extended home visit programme in Sweden, our aim was to illuminate first-time parents' experience of a home visit conducted by a midwife and a child health care nurse 1–2 weeks postnatal.

Methods

Data was collected by interviews (n = 13) with first-time parents. The transcribed texts were analyzed using inductive content analysis.

Results

The participants' experiences could be understood from the two themes, A trust in the professionals and Feeling safe as a new parent. The participants experienced that the midwives and the child health care nurses complemented each other and appreciated to get knowledge and information from both professions. In their own home, they felt secured and relaxed, and the professionals could help them provide a safe home environment for the child.

Conclusion

By meeting both professionals at the same time and in their own home, the participants experienced that the needs of the baby and their needs and concerns as new parents were included and supported.
Case Report and Literature Review: Clinical Characteristics of 10 Children With Mycoplasma pneumoniae-Induced Rash and Mucositis
Authors: Chen Ning , Li Miao
Published: March 2022

Mycoplasma pneumoniae-induced rash and mucositis (MIRM) is a rare disease, which has not been reported in northern China previously. We retrospectively analyzed the clinical characteristics, diagnosis and treatment of 10 cases of MIRM in order to help clinicians to identify MIRM and to distinguish it from the similar mucositis and cutaneous characteristics of Stevens-Johnson syndrome. All 10 children included in the study had MIRM with skin and mucosal symptoms, but the characteristics of the skin and mucosal lesions differed by age. Most of the older children had sparse erythema and a vesicular rash, but the younger children had dense erythema without blisters but with purulent exudation. The mucositis was relatively mild in the younger children. The erythrocyte sedimentation rate, the levels of C-reactive protein, lactate dehydrogenase, and D-dimer were significantly elevated in most children with MIRM. Concomitant treatment of glucocorticoids and/or IVIG with macrolides may shorten the duration of fever and accelerate the clinical recovery. Additional case reports are needed to improve knowledge of the characteristics of MIRM and its response to therapy.
Type 2 Diabetes Complicated With Heart Failure: Research on Therapeutic Mechanism and Potential Drug Development Based on Insulin Signaling Pathway
Authors: Ye Hui , He Yanan , Zheng Chuan , Wang Fang , Yang Ming , Lin Junzhi , Xu Runchun , Zhang Dingkun
Published: March 2022

Type 2 diabetes mellitus (T2DM) and heart failure (HF) are diseases characterized by high morbidity and mortality. They often occur simultaneously and increase the risk of each other. T2DM complicated with HF, as one of the most dangerous disease combinations in modern medicine, is more common in middle-aged and elderly people, making the treatment more difficult. At present, the combination of blood glucose control and anti-heart failure is a common therapy for patients with T2DM complicated with HF, but their effect is not ideal, and many hypoglycemic drugs have the risk of heart failure. Abnormal insulin signaling pathway, as a common pathogenic mechanism in T2DM and HF, could lead to pathological features such as insulin resistance (IR), myocardial energy metabolism disorders, and vascular endothelial disorders. The therapy based on the insulin signaling pathway may become a specific therapeutic target for T2DM patients with HF. Here, we reviewed the mechanisms and potential drugs of insulin signaling pathway in the treatment of T2DM complicated with HF, with a view to opening up a new perspective for the treatment of T2DM patients with HF and the research and development of new drugs.
A Polysaccharide From Eupolyphaga sinensis Walker With Anti-HBV Activities In Vitro and In Vivo
Authors: Zhang Xue , Su Huiling , Yu Haifei , Ding Jialu , Deng Wanyu , Qin Bo , Zhou Changlin , Dou Jie , Guo Min
Published: March 2022

Hepatitis B virus (HBV) infection remains a major global threat to human health worldwide. Recently, the Chinese medicines with antiviral properties and low toxicity have been a concern. In our previous study, Eupolyphaga sinensis Walker polysaccharide (ESPS) has been isolated and characterized, while its antiviral effect on HBV remained unclear. The anti-HBV activity of ESPS and its regulatory pathway were investigated in vitro and in vivo. The results showed that ESPS significantly inhibited the production of HBsAg, HBeAg, and HBV DNA in the supernatants of HepG2.2.15 in a dose-dependent manner; HBV RNA and core protein expression were also decreased by ESPS. The in vivo studies using HBV transgenic mice further revealed that ESPS (20 and 40 mg/kg/2 days) significantly reduced the levels HBsAg, HBeAg, and HBV DNA in the serum, as well as HBV DNA and HBV RNA in mice liver. In addition, ESPS activated the Toll-like receptor 4 (TLR4) pathway; elevated levels of IFN-β, TNF-α, and IL-6 in the serum were observed, indicating that the anti-HBV effect of ESPS was achieved by potentiating innate immunity function. In conclusion, our study shows that ESPS is a potential anti-HBV ingredient and is of great value in the development of new anti-HBV drugs.
Chlorin e6-Induced Photodynamic Effect Polarizes the Macrophage Into an M1 Phenotype Through Oxidative DNA Damage and Activation of STING
Authors: Yu Ting-Ting , Han Ning , Li Liu-Gen , Peng Xing-Chun , Li Qi-Rui , Xu Hua-Zhen , Wang Xi-Yong , Yang Zi-Yi , Chen Xiao , Wang Mei-Fang , Li Tong-Fei
Published: March 2022

The tumor-associated macrophage (TAM) serves as an immunosuppressive agent in the malignant tumor microenvironment, facilitating the development and metastasis of lung cancer. The photodynamic effect destabilizes cellular homeostasis owing to the generation of reactive oxygen species (ROS), resulting in the enhanced pro-inflammatory function of immunocytes. In our previous study, the Ce6-mediated photodynamic effect was found to have kept the viability of macrophages and to remodel them into the M1 phenotype. However, the mechanism remains unrevealed. The present study now explores the mechanism of photodynamic therapy (PDT)-mediated reprogramming of macrophages. As expected, Ce6-mediated PDT was capable of generating reactive oxygen species, which was continuously degraded, causing “low intensity” damage to DNA and thereby triggering subsequent DNA damage response in macrophages. The autophagy was thus observed in Ce6-treated macrophages and was shown to protect cells from being photodynamically apoptotic. More importantly, Ce6 PDT could activate the stimulator of interferon genes (STING) molecule, a sensor of DNA damage, which could activate the downstream nuclear factor kappa-B (NF-κB) upon activation, mediating the polarization of macrophages towards the M1 phenotype thereupon. In addition, inhibition of ROS induced by PDT attenuated the DNA damage, STING activation, and M1-phenotype reprogramming. Furthermore, the silence of the STING weakened Ce6 treatment-mediated M1 remodeling of macrophages as well. Altogether, these findings indicate the Ce6-induced photodynamic effect polarizes macrophages into an M1 phenotype through oxidative DNA damage and subsequent activation of the STING. This work reveals the crucial mechanism by which photodynamic therapy regulates the macrophage phenotype and also provides a novel intervenable signaling target for remodeling macrophages into the M1 phenotype.
Protective Effect of Renin-Angiotensin System Inhibitors on Parkinson’s Disease: A Nationwide Cohort Study
Authors: Jo Youngkwon , Kim Seungyeon , Ye Byoung Seok , Lee Euni , Yu Yun Mi
Published: March 2022

Background: Renin-angiotensin system (RAS) inhibitors have been suggested as protective agents in Parkinson’s disease (PD). However, epidemiological evidence on the association between RAS inhibitors and the development of PD is inconsistent.

Objectives: To investigate the effect of RAS inhibitors on PD risk in patients with ischemic heart disease (IHD) by type and cumulative duration of RAS inhibitors and their degree of blood-brain barrier (BBB) penetration ability.

Methods: This was a propensity score-matched retrospective cohort study using 2008–2019 healthcare claims data from the Korean Health Insurance Review and Assessment database. The association between RAS inhibitor use and PD in patients with IHD was evaluated using multivariate Cox proportional hazard regression analysis. The risks are presented as adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs).

Results: Over a 10-year follow-up, 1,086 of 62,228 IHD patients developed PD. The Cox regression model showed that the use of RAS inhibitors was significantly associated with a lower risk of PD (aHR = 0.75; 95% CI 0.66–0.85) than the non-use of RAS inhibitors. Specifically, this reduced risk of PD only remained with the use of BBB-crossing angiotensin II receptor blockers (ARBs) (aHR = 0.62; 95% CI = 0.53–0.74), and this association was more definite with an increasing cumulative duration. A significantly reduced risk of PD was not observed with the use of BBB-crossing angiotensin-converting enzyme inhibitors.

Conclusions: The use of ARBs with BBB-penetrating properties and a high cumulative duration significantly reduces the risk of PD in IHD patients. This protective effect could provide insight into disease-modifying drug candidates for PD.
Inflammation and Cancer: From the Development of Personalized Indicators to Novel Therapeutic Strategies
Authors: Ballerini Patrizia , Contursi Annalisa , Bruno Annalisa , Mucci Matteo , Tacconelli Stefania , Patrignani Paola
Published: March 2022

Colorectal (CRC) and hepatocellular carcinoma (HCC) are associated with chronic inflammation, which plays a role in tumor development and malignant progression. An unmet medical need in these settings is the availability of sensitive and specific noninvasive biomarkers. Their use will allow surveillance of high-risk populations, early detection, and monitoring of disease progression. Moreover, the characterization of specific fingerprints of patients with nonalcoholic fatty liver disease (NAFLD) without or with nonalcoholic steatohepatitis (NASH) at the early stages of liver fibrosis is necessary. Some lines of evidence show the contribution of platelets to intestinal and liver inflammation. Thus, low-dose Aspirin, an antiplatelet agent, reduces CRC and liver cancer incidence and mortality. Aspirin also produces antifibrotic effects in NAFLD. Activated platelets can trigger chronic inflammation and tissue fibrosis via the release of soluble mediators, such as thromboxane (TX) A2 and tumor growth factor (TGF)-β, and vesicles containing genetic material (including microRNA). These platelet-derived products contribute to cyclooxygenase (COX)-2 expression and prostaglandin (PG)E2 biosynthesis by tumor microenvironment cells, such as immune and endothelial cells and fibroblasts, alongside cancer cells. Enhanced COX-2-dependent PGE2 plays a crucial role in chronic inflammation and promotes tumor progression, angiogenesis, and metastasis. Antiplatelet agents can indirectly prevent the induction of COX-2 in target cells by inhibiting platelet activation. Differently, selective COX-2 inhibitors (coxibs) block the activity of COX-2 expressed in the tumor microenvironment and cancer cells. However, coxib chemopreventive effects are hampered by the interference with cardiovascular homeostasis via the coincident inhibition of vascular COX-2-dependent prostacyclin biosynthesis, resulting in enhanced risk of atherothrombosis. A strategy to improve anti-inflammatory agents’ use in cancer prevention could be to develop tissue-specific drug delivery systems. Platelet ability to interact with tumor cells and transfer their molecular cargo can be employed to design platelet-mediated drug delivery systems to enhance the efficacy and reduce toxicity associated with anti-inflammatory agents in these settings. Another peculiarity of platelets is their capability to uptake proteins and transcripts from the circulation. Thus, cancer patient platelets show specific proteomic and transcriptomic expression profiles that could be used as biomarkers for early cancer detection and disease monitoring.
Morus alba L. (Sangzhi) Alkaloids Promote Insulin Secretion, Restore Diabetic β-Cell Function by Preventing Dedifferentiation and Apoptosis
Authors: Lei Lei , Huan Yi , Liu Quan , Li Caina , Cao Hui , Ji Wenming , Gao Xuefeng , Fu Yaxin , Li Pingping , Zhang Ruiping , Abliz Zeper , Liu Yuling , Liu Shuainan , Shen Zhufang
Published: March 2022

Background:Morus alba L. (Sangzhi) alkaloids (SZ-A), extracted from the Chinese herb Morus alba L. (mulberry twig), have been shown to ameliorate hyperglycemia in type 2 diabetes and have been approved for diabetes treatment in the clinic. However, their versatile pharmacologic effects and regulatory mechanisms are not yet completely understood.

Purpose: This study explored the protective effects of SZ-A on islet β cells and the underlying mechanism.

Methods: Type 2 diabetic KKAy mice were orally administered SZ-A (100 or 200 mg/kg, once daily) for 11 weeks, and oral glucose tolerance, insulin tolerance, intraperitoneal glucose tolerance and hyperglycemia clamp tests were carried out to evaluate the potency of SZ-A in vivo. The morphology and β-cell dedifferentiation marker of KKAy mouse islets were detected via immunofluorescence. The effect of SZ-A on glucose-stimulated insulin secretion was investigated in both the islet β-cell line MIN6 and mouse primary islets. Potential regulatory signals and pathways in insulin secretion were explored, and cell proliferation assays and apoptosis TUNEL staining were performed on SZ-A-treated MIN6 cells.

Results: SZ-A alleviated hyperglycemia and glucose intolerance in type 2 diabetic KKAy mice and improved the function and morphology of diabetic islets. In both MIN6 cells and primary islets, SZ-A promoted insulin secretion. At a normal glucose level, SZ-A decreased AMPKα phosphorylation, and at high glucose, SZ-A augmented the cytosolic calcium concentration. Additionally, SZ-A downregulated the β-cell dedifferentiation marker ALDH1A3 and upregulated β-cell identifying genes, such as Ins1, Ins2, Nkx2.2 and Pax4 in KKAy mice islets. At the same time, SZ-A attenuated glucolipotoxicity-induced apoptosis in MIN6 cells, and inhibited Erk1/2 phosphorylation and caspase 3 activity. The major active fractions of SZ-A, namely DNJ, FAG and DAB, participated in the above regulatory effects.

Conclusion: Our findings suggest that SZ-A promotes insulin secretion in islet β cells and ameliorates β-cell dysfunction and mass reduction under diabetic conditions both in vivo and in vitro, providing additional supportive evidence for the clinical application of SZ-A.
Difficulty in Repurposing Selective Serotonin Reuptake Inhibitors and Other Antidepressants with Functional Inhibition of Acid Sphingomyelinase in COVID-19 Infection
Authors: Le Corre Pascal , Loas Gwenolé
Published: March 2022

The rapid spread of COVID-19 has become a health emergency causing an urgent need for drug treatments to control the outbreak, especially in more vulnerable individuals. This is reinforced by the fact that prophylactic vaccines and neutralizing monoclonal antibodies may not be fully effective against emerging variants. Despite all efforts made by the scientific community, efficient therapeutic options currently remain scarce, either in the initial, as well as in the advanced forms of the disease. From retrospective observational studies and prospective clinical trials, selective serotonin reuptake inhibitors (SSRIs), and other antidepressants with functional inhibition of acid sphingomyelinase (FIASMAs), have emerged as potential treatments of COVID-19. This has led to some prematurely optimistic points of view, promoting a large prescription of fluvoxamine in patients with COVID-19, that we think should be reasonably tempered.
Pharmacological Effects and Molecular Protective Mechanisms of Astragalus Polysaccharides on Nonalcoholic Fatty Liver Disease
Authors: Zhang Jing , Feng Quansheng
Published: March 2022

Nonalcoholic fatty liver disease (NAFLD) has been renamed metabolic dysfunction-associated fatty liver disease (MAFLD), a condition for which there is now no authorized treatment. The search for new medications to treat MAFLD made from natural substances is gaining traction. The function of anti-oxidant, anti-inflammation, hypoglycaemic, antiviral, hypolipidemic, and immunomodulatory actions of Astragalus polysaccharides (APS), a chemical molecule isolated from Astragalus membranaceus, has become the focus of therapeutic attention. We have a large number of papers on the pharmacological effects of APS on NAFLD that have never been systematically reviewed before. According to our findings, APS may help to slow the progression of non-alcoholic fatty liver disease (NAFL) to non-alcoholic steatohepatitis (NASH). Lipid metabolism, insulin resistance (IR), oxidative stress (OS), endoplasmic reticulum stress (ERS), inflammation, fibrosis, autophagy, and apoptosis are some of the pathogenic pathways involved. SIRT1/PPARα/FGF21, PI3K/AKT/IRS-1, AMPK/ACC, mTOR/4EBP-1/S6K1, GRP78/IRE-1/JNK, AMPK/PGC-1/NRF1, TLR4/MyD88/NF-κB, and TGF-β/Smad pathways were the most common molecular protective mechanisms. All of the information presented in this review suggests that APS is a natural medication with a lot of promise for NAFLD, but more study, bioavailability studies, medicine type and dosage, and clinical proof are needed. This review could be useful for basic research, pharmacological development, and therapeutic applications of APS in the management of MAFLD.
Multi-Pass Free Electron Laser Assisted Spectral and Imaging Applications in the Terahertz/Far-IR Range Using the Future Superconducting Electron Source BriXSinO
Authors: Koral Can , Mazaheri Zahra , Papari Gian Paolo , Andreone Antonello , Drebot Illya , Giove Dario , Masullo Maria Rosaria , Mettivier Giovanni , Opromolla Michele , Paparo Domenico , Passarelli Andrea , Petrillo Vittoria , Piccirillo Bruno , Rubano Andrea , Ruijter Marcel , Russo Paolo , Serafini Luca
Published: March 2022

Free-Electron Lasers are a rapidly growing field for advanced science and applications, and worldwide facilities for intense field generation, characterization and usage are becoming increasingly popular due to their peculiarities, including extremely bright, coherent, wide band tunable ultra-short pulses which are not achievable with other techniques up to now. In this review we give a thorough survey of the latest advances in the Free-Electron Laser-based field generation and detection methodologies and then present the main characteristics of a future THz/IR source, named TerRa@BriXSinO, based on a superconducting linear accelerator. The foreseen source is strongly monochromatic, with a bandwidth of 1% or smaller, highly coherent both transversally and longitudinally, with extreme versatility and high frequency tunability. After introducing the most recent and novel FEL-assisted scientific investigations, including fundamental explorations into complex systems and time-dependent interactions and material dynamics, we present our vision on the potential use of the TerRa facility and analyze some possible applications, ranging from non-linear physics under extreme conditions to polarization sensitive imaging and metamaterial-based sensing.
The Eccentric Phase in Unilateral Resistance Training Enhances and Preserves the Contralateral Knee Extensors Strength Gains After Detraining in Women: A Randomized Controlled Trial
Authors: Coratella Giuseppe , Galas Annalisa , Campa Francesco , Pedrinolla Anna , Schena Federico , Venturelli Massimo
Published: March 2022

The current randomized controlled study investigated whether or not the inclusion of the eccentric phase in resistance training favors the contralateral strength gains after different unilateral protocols, and whether such gains are retained after detraining. Sixty healthy women were randomly assigned to a unilateral concentric-only (CONC), eccentric-only (ECC), concentric–eccentric (TRAD) volume-equated knee extension training or control group (CON). The participants trained 2 days/week for 8 weeks and then did not train for further 8 weeks. Knee extensors isokinetic concentric, eccentric, and isometric peak torque and vastus lateralis muscle thickness were assessed in the contralateral limb at baseline, post-training, and post-detraining. At post-training, concentric peak torque increased in CONC [+9.2%, 95%CI (+6.2/+12.3), p < 0.001, ES: 0.70, 95%CI (0.01/1.39)], ECC [+11.0% (+7.7/+14.2), p < 0.001: ES: 0.66(0.09/1.23)] and TRAD [+8.5%(+5.7/+11.6), p < 0.001, ES: 0.50(0.02/0.98)]. Eccentric peak torque increased in ECC in ECC [+15.0%(+11.4/+20.7), p < 0.001, ES: 0.91(0.14/1.63)] and TRAD [+5.5%(+0.3/10.7), p = 0.013, ES: 0.50(0.05/0.95)]. Isometric peak torque increased in ECC [+11.3(+5.8/16.8), p < 0.001, ES: 0.52(0.10/0.94)] and TRAD [+8.6%(+3.4/+13.7), p < 0.001, ES: 0.55(0.14/0.96)]. No change in eccentric and isometric peak torque occurred in CONC (p > 0.05). Muscle thickness did not change in any group (p > 0.05). At post-detraining, all groups preserved the contralateral strength gains observed at post-training (p < 0.05). The findings showed that ECC and TRAD increased contralateral knee extensors strength in concentric, eccentric, and isometric modality, while CONC only increased concentric strength. The eccentric phase appears to amplify the cross-education effect, permitting a transfer in strength gaining toward multiple testing modalities. Both eccentric-based and traditional eccentric–concentric resistance protocols are recommended to increase the contralateral retention in strength gains after a detraining period.
Adult Health and Early Life Adversity: Behind the Curtains of Maternal Care Research
Authors: Dumas Theodore C.
Published: March 2022

The quality of one’s adult health and the chances of maintaining cognitive ability in aging stem directly from the quality of care one receives as an infant. Formal studies of maternal care can be traced back at least a century. Revelations of behavioral outcomes after maternal deprivation in primates were followed by discoveries of systemic and brain growth factors mediated by the caregiver–offspring relationship in rodents. More recently, much of the genetic/epigenetic bases of maternal care has been defined and positively linked to adult health and cognitive ability in senescence. The history of this field is both tragic and fascinating. The early primate work, while informative, was abusive. The initial rodent work was ridiculed before its importance was recognized. The final lesson learned is that infant/toddler care matters a lot. Today, we have a better understanding of the biology underlying maternal care and its transmission across generations as well as a scientific basis for massaging premature infants and hugging our children.
The ISPAInt Injury Prevention Programme for Youth Competitive Alpine Skiers: A Controlled 12-Month Experimental Study in a Real-World Training Setting
Authors: Schoeb Thierry , Fröhlich Stefan , Frey Walter O. , Verhagen Evert , Farshad Mazda , Spörri Jörg
Published: March 2022

Evidence-based injury prevention programmes for youth competitive alpine skiers are widely absent. The aims of this controlled 12-month experimental study were to introduce a novel injury prevention programme targeted to the injury patterns of youth skiers, called ISPAInt, and to compare the differences in injury occurrence between an intervention group (IG) additionally performing the ISPAInt programme and an independent, historical control group (CG) following their regular training routines. None of the skiers of the CG were part of the IG and vice versa. The study was directly conducted within the real-world youth development structures of skiers competing at the under 16 years (U16) level in Switzerland. Seventy-one skiers (aged 14.4 ± 0.3 years) assigned to the IG were compared to 58 age- and gender-matched controls. The IG was offered the ISPAInt programme with the recommendation to perform it at least once per week. Skiers’ adherence to this recommendation was surveyed but not enforced. Injuries were recorded using the Oslo Sports Trauma Research Centre Questionnaire. Primary outcomes were the absolute injury rates (number of injuries/100 athletes per season) and epidemiological incidence proportion (number of injured athletes/100 athletes per season). The secondary outcome was the average 2-weekly prevalence of traumatic knee, knee overuse, and lower back overuse injuries. There were lower absolute rates of all traumatic injuries [rate/risk difference, RD: −57.1 (−98.1, −16.0); rate/risk ratio, RR: 0.665 (0.485, 0.884)] and overuse injuries [RD: −35.9 (−71.0, −0.7); RR: 0.699 (0.493, 0.989)] in the IG than in the CG. Likewise, the epidemiological incidence proportion for all overuse injuries was smaller in the IG [RD: −28.4 (−44.8, −12.0); RR: 0.598 (0.435, 0.822)], while the proportion of skiers suffering from traumatic injuries did not significantly differ between the groups. Notably, the IG particularity differed from the CG in the average 2-weekly prevalence of knee trauma, knee overuse, and lower back overuse complaints, three of the major injury-related hot spots in youth skiers. Based on these promising results, the ISPAInt programme may have great potential to prevent injuries in youth competitive alpine skiers, and the underlying exercises should be considered complementary training content at the U16 level.
Muscle Fatigue and Swimming Efficiency in Behind and Lateral Drafting
Authors: Puce Luca , Chamari Karim , Marinelli Lucio , Mori Laura , Bove Marco , Faelli Emanuela , Fassone Marco , Cotellessa Filippo , Bragazzi Nicola Luigi , Trompetto Carlo
Published: March 2022

Drafting in swimming is a tactic in which an athlete (drafter) swims in the wave of another athlete (leader). Our aim was to compare the effects of this tactic on the drafter, as far as muscle fatigue, muscle activity, and swimming efficiency are concerned. Fifteen drafters performed three 200 m front crawl trials at a controlled submaximal pace in three configurations: Behind Drafting (BD), Lateral Drafting (LD), and Free Swimming (FS). Muscle fatigue, muscle activity, and swimming efficiency were obtained by surface electromyography (EMG) and video analysis from flexor carpi radialis, triceps brachii, latissimus dorsi, and rectus femoris muscles. The outcome measures were: time slope of Mean Frequency (MNF), for muscle fatigue; time slope of Root Mean Square (RMS), for muscle activity; and Stroke Index (SI) for swimming efficiency. Negative variations of MNF were 5.1 ± 1.7%, 6.6 ± 4.1%, and 11.1 ± 2.7% in BD, LD, and FS, respectively. Statistical significance was found for all cases except for the rectus femoris. Positive variations of RMS were 3.4 ± 1.2%, 4.7 ± 2.7%, and 7.8 ± 4.6% in BD, LD, and FS, respectively. Statistical significance was found only for the slopes of latissimus dorsi in FS and LD. The largest mean in SI was measured in the BD (2.01 m2/s), while the smallest was measured in the FS (1.86 m2/s). BD was found to be the best swimming configuration, in terms of lower muscle fatigue and higher swimming efficiency. Also, LD resulted to be advantageous with respect to FS.
Vitreous Inflammatory Cytokines and Chemokines, Not Altered After Preoperative Adjunctive Conbercept Injection, but Associated With Early Postoperative Macular Edema in Patients With Proliferative Diabetic Retinopathy
Authors: Sun Hongyan , Zou Wenjun , Zhang Zhengyu , Huang Darui , Zhao Jinxiang , Qin Bing , Xie Ping , Mugisha Aime , Liu Qinghuai , Hu Zizhong
Published: March 2022

Purpose

To investigate the influence of preoperative adjunctive anti-VEGF drug (Conbercept) on vitreous inflammatory cytokines and chemokines profiles and whether those cytokines were associated with early macular edema (ME) after surgery for patients with proliferative diabetic retinopathy (PDR).

Methods

In this post hoc analysis of the CONCEPT clinical trial, subjects with PDR underwent vitrectomy were included and vitreous samples were collected at the start of vitrectomy. Levels of vitreous VEGF, 17 inflammatory cytokines, and 11 chemokines were measured using Luminex multiplex technology. Subjects were then divided into groups based on with (Pre-IV) or without (No-Pre-IV) preoperative intravitreous injection of Conbercept; with or without early ME after surgery.

Results

There was no difference between Pre-IV (13/30) and No-Pre-IV (7/29) concerning the ratio of patients with early ME (p = 0.17). After preoperative intravitreous injection of Conbercept, VEGF level dramatically decreased (p = 0.001), TNF-α (p = 0.002), and IP-10 (p = 0.018) increased in Pre-IV group. In patients with early ME after surgery, however, a number of cytokines increased, including IL-1β (p = 0.008), IL-2 (p = 0.023), IL-4 (p = 0.030), IL-9 (p = 0.02), IL-10 (p = 0.002), IL-12 (p = 0.001), IL-13 (p = 0.031), IL-17A (p = 0.008), TNF-α (p = 0.012), CXCL9 (p = 0.023), G-CSF (p = 0.019), MCP-1 (p = 0.048), and RANTES (p = 0.016).

Conclusion

We found the preoperative adjunctive Conbercept injection has limited influence on the levels of vitreous inflammatory cytokines and chemokines in PDR. The elevated levels of a series of cytokines might be associated with early inflammation after vitrectomy, which may lead to postoperative ME.
Environment Characterization in Sorghum (Sorghum bicolor L.) by Modeling Water-Deficit and Heat Patterns in the Great Plains Region, United States
Authors: Carcedo Ana J. P. , Mayor Laura , Demarco Paula , Morris Geoffrey P. , Lingenfelser Jane , Messina Carlos D. , Ciampitti Ignacio A.
Published: March 2022

Environmental characterization for defining the target population of environments (TPE) is critical to improve the efficiency of breeding programs in crops, such as sorghum (Sorghum bicolorL.). The aim of this study was to characterize the spatial and temporal variation for a TPE for sorghum within the United States. APSIM-sorghum, included in the Agricultural Production Systems sIMulator software platform, was used to quantify water-deficit and heat patterns for 15 sites in the sorghum belt. Historical weather data (∼35 years) was used to identify water (WSP) and heat (HSP) stress patterns to develop water–heat clusters. Four WSPs were identified with large differences in the timing of onset, intensity, and duration of the stress. In the western region of Kansas, Oklahoma, and Texas, the most frequent WSP (∼35%) was stress during grain filling with late recovery. For northeast Kansas, WSP frequencies were more evenly distributed, suggesting large temporal variation. Three HSPs were defined, with the low HSP being most frequent (∼68%). Field data from Kansas State University sorghum hybrid yield performance trials (2006–2013 period, 6 hybrids, 10 sites, 46 site × year combinations) were classified into the previously defined WSP and HSP clusters. As the intensity of the environmental stress increased, there was a clear reduction on grain yield. Both simulated and observed yield data showed similar yield trends when the level of heat or water stressed increased. Field yield data clearly separated contrasting clusters for both water and heat patterns (with vs. without stress). Thus, the patterns were regrouped into four categories, which account for the observed genotype by environment interaction (GxE) and can be applied in a breeding program. A better definition of TPE to improve predictability of GxE could accelerate genetic gains and help bridge the gap between breeders, agronomists, and farmers.
MSR-RCNN: A Multi-Class Crop Pest Detection Network Based on a Multi-Scale Super-Resolution Feature Enhancement Module
Authors: Teng Yue , Zhang Jie , Dong Shifeng , Zheng Shijian , Liu Liu
Published: March 2022

Pest disaster severely reduces crop yield and recognizing them remains a challenging research topic. Existing methods have not fully considered the pest disaster characteristics including object distribution and position requirement, leading to unsatisfactory performance. To address this issue, we propose a robust pest detection network by two customized core designs: multi-scale super-resolution (MSR) feature enhancement module and Soft-IoU (SI) mechanism. The MSR (a plug-and-play module) is employed to improve the detection performance of small-size, multi-scale, and high-similarity pests. It enhances the feature expression ability by using a super-resolution component, a feature fusion mechanism, and a feature weighting mechanism. The SI aims to emphasize the position-based detection requirement by distinguishing the performance of different predictions with the same Intersection over Union (IoU). In addition, to prosper the development of agricultural pest detection, we contribute a large-scale light-trap pest dataset (named LLPD-26), which contains 26-class pests and 18,585 images with high-quality pest detection and classification annotations. Extensive experimental results over multi-class pests demonstrate that our proposed method achieves the best performance by 67.4% of mAP on the LLPD-26 while being 15.0 and 2.7% gain than state-of-the-art pest detection AF-RCNN and HGLA respectively. Ablation studies verify the effectiveness of the proposed components.