bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperandrogenism and menstrual imbalance are the best predictors of metformin response in PCOS patients
Authors: Garzia Emanuele , Galiano Valentina , Marfia Giovanni , Navone Stefania , Grossi Enzo , Marconi Anna Maria 
Published: January 2022

Abstract
Background
Moving from the correlation between insulin-resistance and PCOS, metformin has been administered in some PCOS women improving ovulatory and metabolic functions and decreasing androgen levels. Inconsistency and unpredictability of response to metformin limit its extensive use. Aim of this study was to identify reliable predictors of response to metformin therapy for weight loss and reduction in plasma androgen levels using ANNs (artificial neural networks).

Methods
One hundred eight consecutive women with PCOS (ESHRE/ASRM 2003 Rotterdam criteria) treated with metformin 1500 mg/day, at inclusion and every 6 months underwent to a complete clinical, endocrine/metabolic assessment and ultrasonographic evaluation. Therapy outcomes were BMI reduction (≥1 kg/m2) in overweight/obese and free-androgen-index (FAI) decrease (≥1%) in hyperandrogenemic women. Semantic connectivity maps (SCMs) were obtained through Auto-CM, a fourth generation ANN, to compare patients’ baseline clinical features to the treatment outcomes. Multivariate logistic regression analysis was used to assess the major predictor in drop-out patients and the associated risk.

Results
At 6 months 54 out of 103 (52,4%) obese patients showed BMI reduction and 45 out of 89 (50,6%) hyperandrogenemic women showed FAI decrease. The further response rates at 12 months were 30,6 and 47%, respectively. SCMs showed a clear polarization for both the outcomes with elevated accuracy. Treatment responsiveness resulted strictly related to oligo-amenorrhea and hyperandrogenemia at baseline. In addition, lower serum testosterone levels at baseline were found to be the major predictor of treatment discontinuation.

Conclusions
In women with PCOS, menstrual pattern imbalance and ovarian androgens excess are the best predictors of metformin response. They may pave the way for a rethinking of the criteria for evaluating hyperandrogenism in order to better define the large population included in the diagnosis of PCOS. Baseline plasma testosterone level can serve as a sensitive marker to predict treatment compliance.
Social isolation induces neuroinflammation and microglia overactivation, while dihydromyricetin prevents and improves them
Authors: Al Omran Alzahra J. , Shao Amy S. , Watanabe Saki , Zhang Zeyu , Zhang Jifeng , Xue Chen , Watanabe Junji , Davies Daryl L. , Shao Xuesi M. , Liang Jing 
Published: January 2022

Abstract
Background
Anxiety disorders are the most prevalent mental illnesses in the U.S. and are estimated to consume one-third of the country’s mental health treatment cost. Although anxiolytic therapies are available, many patients still exhibit treatment resistance, relapse, or substantial side effects. Further, due to the COVID-19 pandemic and stay-at-home order, social isolation, fear of the pandemic, and unprecedented times, the incidence of anxiety has dramatically increased. Previously, we have demonstrated dihydromyricetin (DHM), the major bioactive flavonoid extracted from Ampelopsis grossedentata, exhibits anxiolytic properties in a mouse model of social isolation-induced anxiety. Because GABAergic transmission modulates the immune system in addition to the inhibitory signal transmission, we investigated the effects of short-term social isolation on the neuroimmune system.

Methods
Eight-week-old male C57BL/6 mice were housed under absolute social isolation for 4 weeks. The anxiety-like behaviors after DHM treatment were examined using elevated plus-maze and open field behavioral tests. Gephyrin protein expression, microglial profile changes, NF-κB pathway activation, cytokine level, and serum corticosterone were measured.

Results
Socially isolated mice showed increased anxiety levels, reduced exploratory behaviors, and reduced gephyrin levels. Also, a dynamic alteration in hippocampal microglia were detected illustrated as a decline in microglia number and overactivation as determined by significant morphological changes including decreases in lacunarity, perimeter, and cell size and increase in cell density. Moreover, social isolation induced an increase in serum corticosterone level and activation in NF-κB pathway. Notably, DHM treatment counteracted these changes.

Conclusion
The results suggest that social isolation contributes to neuroinflammation, while DHM has the ability to improve neuroinflammation induced by anxiety.
Health risks and mitigation strategies from occupational exposure to wildland fire: a scoping review
Authors: Koopmans Erica , Cornish Katie , Fyfe Trina M. , Bailey Katherine , Pelletier Chelsea A. 
Published: January 2022

Abstract
Objectives
Due to accelerating wildland fire activity, there is mounting urgency to understand, prevent, and mitigate the occupational health impacts associated with wildland fire suppression. The objectives of this review of academic and grey literature were to:

Identify the impact of occupational exposure to wildland fires on physical, mental, and emotional health; and

Examine the characteristics and effectiveness of prevention, mitigation, or management strategies studied to reduce negative health outcomes associated with occupational exposure to wildland fire.

Methods
Following established scoping review methods, academic literature as well as government and industry reports were identified by searching seven academic databases and through a targeted grey literature search. 4679 articles were screened using pre-determined eligibility criteria. Data on study characteristics, health outcomes assessed, prevention or mitigation strategies studied, and main findings were extracted from each included document. The results of this scoping review are presented using descriptive tables and a narrative summary to organize key findings.

Results
The final sample was comprised of 100 articles: 76 research articles and 24 grey literature reports. Grey literature focused on acute injuries and fatalities. Health outcomes reported in academic studies focused on respiratory health (n = 14), mental health (n = 16), and inflammation and oxidative stress (n = 12). The identified studies evaluated short-term outcomes measuring changes across a single shift or wildland fire season. Most research was conducted with wildland firefighters and excluded personnel such as aviation crews, contract crews, and incident management teams. Five articles reported direct study of mitigation strategies, focusing on the potential usage of masks, advanced hygiene protocols to reduce exposure, fluid intake to manage hydration and core temperature, and glutamine supplementation to reduce fatigue.

Conclusions
While broad in scope, the evidence base linking wildland fire exposure to any one health outcome is limited. The lack of long-term evidence on changes in health status or morbidity is a clear evidence gap and there is a need to prioritize research on the mental and physical health impact of occupational exposure to wildland fire.
High throughput phenotyping of cross-sectional morphology to assess stalk lodging resistance
Authors: Oduntan Yusuf A. , Stubbs Christopher J. , Robertson Daniel J. 
Published: January 2022

Abstract
Background
Stalk lodging (mechanical failure of plant stems during windstorms) leads to global yield losses in cereal crops estimated to range from 5% to 25% annually. The cross-sectional morphology of plant stalks is a key determinant of stalk lodging resistance. However, previously developed techniques for quantifying cross-sectional morphology of plant stalks are relatively low-throughput, expensive and often require specialized equipment and expertise. There is need for a simple and cost-effective technique to quantify plant traits related to stalk lodging resistance in a high-throughput manner.

Results
A new phenotyping methodology was developed and applied to a range of plant samples including, maize (Zea mays), sorghum (Sorghum bicolor), wheat (Triticum aestivum), poison hemlock (Conium maculatum), and Arabidopsis (Arabis thaliana). The major diameter, minor diameter, rind thickness and number of vascular bundles were quantified for each of these plant types. Linear correlation analyses demonstrated strong agreement between the newly developed method and more time-consuming manual techniques (R2 > 0.9). In addition, the new method was used to generate several specimen-specific finite element models of plant stalks. All the models compiled without issue and were successfully imported into finite element software for analysis. All the models demonstrated reasonable and stable solutions when subjected to realistic applied loads.

Conclusions
A rapid, low-cost, and user-friendly phenotyping methodology was developed to quantify two-dimensional plant cross-sections. The methodology offers reduced sample preparation time and cost as compared to previously developed techniques. The new methodology employs a stereoscope and a semi-automated image processing algorithm. The algorithm can be used to produce specimen-specific, dimensionally accurate computational models (including finite element models) of plant stalks.
Market access of Chinese patent medicine products to healthcare security system in China: implications for international integration of traditional medicine into health systems
Authors: Xia Chenglai , Yao Dongning , Lai Yunfeng , Xue Yan , Hu Hao 
Published: January 2022

Abstract
Background
China has introduced a series of polices and practice to manage the market access of Chinese patent medicine (CPM) products into its healthcare security system, which is less analyzed and reported in current literature. Therefore, this paper aimed to investigate the mechanisms managing market access of CPM products into healthcare security system in China, expecting to provide implications for international integration of traditional medicine products into health systems.

Method
This paper used a documentary analysis approach as a qualitative research method. Data were collected from four sources and analyzed in a thematic way.

Results
Four mechanisms to manage entry, price adjustment, and exit of innovative brand and generic CPM products are identified, including: (1) price negotiation, mechanism of new entry of innovative brand CPM products into the national reimbursement list; (2) price re-negotiation, mechanism of price adjustment of innovative brand CPM products within the national reimbursement list; (3) mass procurement, mechanism of generic CPM products to healthcare security system; and (4) direct removal, mechanism of removal from the national reimbursement list.

Conclusions
China has established market access framework of CPM products by focusing on price negotiation for innovative brand CPM products and mass procurement for generic CPM products. Further studies of CPM products based real-world data are needed to provide clinical and pharmacoeconomic evidence to support market access of CPM products into healthcare security systems.
Repurposing a clinically approved prescription Colquhounia root tablet to treat diabetic kidney disease via suppressing PI3K/AKT/NF-kB activation
Authors: Ma Zhaochen , Liu Yudong , Li Congchong , Zhang Yanqiong , Lin Na 
Published: January 2022

AbstractBackgroundGrowing clinical evidences show the potentials of Colquhounia root tablet (CRT) in alleviating diabetic kidney disease (DKD). However, its pharmacological properties and underlying mechanisms remain unclear.Methods‘Drug target-Disease gene’ interaction network was constructed and the candidate network targets were screened through evaluating node genes' topological importance. Then, a DKD rat model induced by high-fat diet/streptozotocin was established and used to determine pharmacological effects and network regulatory mechanisms of CRT against DKD, which were also verified using HK2 cell model induced by high glucose.ResultsThe candidate network targets of CRT against DKD were involved into various type II diabetes-related and nephropathy-related pathways. Due to the topological importance of the candidate network targets and the important role of the imbalance between immunity and inflammation in the pathogenesis of DKD, PI3K/AKT/NF-кB signaling-mediated immune-modulatory and anti-inflammatory actions of CRT were selected to be experimentally verified. On the basis of high-fat diet (HFD) / streptozotocin (STZ)-induced DKD rat model, CRT effectively reduced the elevated level of blood glucose, decreased the accumulation of renal lipid, suppressed inflammation and the generation of ECM proteins, and ameliorated kidney function and the renal histopathology through inhibiting the activation of PI3K, AKT and NF-кB proteins, reducing the nuclear accumulation of NF-кB protein and the serum levels of downstream cytokines, which were in line with the in vitro findings.ConclusionsOur data suggest that CRT may be the promising candidate drug for treating DKD via reversing the imbalance of immune-inflammation system mediated by the PI3K/AKT/NF-кB/IL-1β/TNF-α signaling.
Qingwei San treats oral ulcer subjected to stomach heat syndrome in db/db mice by targeting TLR4/MyD88/NF-κB pathway
Authors: Shi Lu , An Yongcheng , Cheng Long , Li Yiyang , Li Huimin , Wang Chen , Lv Yinglan , Duan Yuhui , Dai Hongyu , He Changhao , Zhang Huilin , Huang Yan , Fu Wanxin , Wang ShengPeng , Zhao Baosheng , Wang Yitao , Zhao Yonghua 
Published: January 2022

Abstract
Background
Qingwei San (QWS), one of classic Chinese Medicine prescripts, has been widely used to treat stomach heat syndrome which manifests oral ulcer (OU), periodontitis and upper gastrointestinal bleeding for seven hundred years. However, the therapeutic effects of QWS on diabetic OU subjected to stomach heat syndrome are still ambiguous. In the study, we investigated the pharmacological mechanisms.

Methods
The main components of QWS aqueous extract were analyzed by LC–MS, and potential pathways of QWS targeting OU were predicted by network pharmacology. The db/db mice were administered with the decoction of dried Zingiber officinale Rosc. rhizome combined with NaOH cauterization to establish the model of diabetic OU subjected to stomach heat syndrome. Subsequently, the model mice were treated with QWS, and OU wound healing status were recorded. The pathological changes of gastric tissue and oral mucosa were evaluated using hematoxylin–eosin staining, and the morphology of collagen fibers in oral mucosa was assessed by Masson staining. The levels of thromboxane B2 (TXB2), 6-Keto-prostaglandin F1α (6-keto-PGF1α), interleukin-1 β (IL-1β), IL-2, IL-6, tumor necrosis factor-α (TNF-α), β-endorphin (β-EP) and 5-Hydroxytryptamine (5-HT) were determined by ELISA assay. The protein expressions of Toll-like receptor 4 (TLR4), TNF receptor associated factor 6 (TRAF6), myeloid differentiation factor 88 (MyD88), inhibitor of NF-κB alpha (IκΒα), p-IκΒα and nuclear factor kappa-B (NF-κB) p65 were measured by Western Blotting.

Results
A total of 183 compounds in QWS were identified by LC–MS, and identified 79 bioactive compounds corresponded to 269 targets and 59 pathways. QWS high-dose treatment significantly reduced the level of TXB2 and the ratio of TXB2/6-keto-PGF1α. Meanwhile, it improved mucosal pathological morphology, and reduced the area of OU and local edema. Simultaneously, the levels of TNF-α, IL-1β, IL-6, IL-2 and 5-HT, and the expressions of TLR4, TRAF6, MyD88, p-IκΒα and NF-κB p65 were decreased.

Conclusion
QWS treatment facilitates the healing of OU, ameliorates pathological morphologies of gastric and oral mucosa and decreases the levels of pro-inflammatory cytokines in db/db mice subjected to stomach heat syndrome, whose mechanism may be associated with the inhibition of TLR4/MyD88/NF-κB signaling pathway to exert anti-inflammatory effects.
The attitude of patients with progressive ataxias towards clinical trials
Authors: Thomas-Black Gilbert , Dumitrascu Andrada , Garcia-Moreno Hector , Vallortigara Julie , Greenfield Julie , Hunt Barry , Walther Susan , Wells Mackenzie , Lynch David R. , Montgomery Hugh , Giunti Paola 
Published: January 2022

AbstractBackgroundThe development of new therapies may rely on the conduct of human experimentation as well as later clinical trials of therapeutic interventions. Ethical considerations seek to protect the patient from risk but few have sought to ascertain the attitude to such risk of patients with progressive debilitating or terminal conditions, for which no mitigating or curative therapies exist. Such understanding is also important if recruitment is to be maximized. We therefore sought to define the motivations for and barriers to trial participation amongst patients with progressive ataxias, as well as their condition-specific trial preferences.MethodsWe conducted an online survey consisting of 29 questions covering four key domains (demographics, personal motivation, drug therapy and study design) relating to the design of clinical trials. Two major ataxia charities, Ataxia UK and the Friedreich’s Ataxia Research Alliance (FARA) sent the survey to their members. Responses were analysed by disease and by ambulatory status.ResultsOf 342 respondents, 204 reported a diagnosis of Friedreich’s ataxia (FRDA), 55 inherited cerebellar ataxia (CA) and 70 idiopathic CA. The most important symptoms to be addressed by a trial were considered to be balance problems and ambulation, although these were superseded by speech problems in wheelchair users. Common motivations for participation were potential benefits to self and others. Reasons for non-participation included concerns about side effects, and the burden and cost of travel. Financial reimbursement for expenses was reported to be likely to increase trial engagement, Phase two trials were the most popular to participate in, and the use of a placebo arm was seen as a disincentive. Across all disease subgroups, drug repurposing trials proved popular and just under 70% of participants would be prepared to undergo intrathecal drug administration.ConclusionsKnowledge of motivations for and barriers to trial participation as well as the acceptability of investigations, time commitments and routes of drug administration should inform better, more patient focused trial design. This in turn may improve recruitment and retention of participants to future trials.
A post pandemic roadmap toward remote assessment for neuromuscular disorders: limitations and opportunities
Authors: Montes Jacqueline , Eichinger Katy J. , Pasternak Amy , Yochai Cara , Krosschell Kristin J. 
Published: January 2022

AbstractRecent advances in technology and expanding therapeutic opportunities in neuromuscular disorders has resulted in greater interest in and development of remote assessments. Over the past year, the rapid and abrupt COVID-19 shutdowns and stay-at-home orders imposed challenges to routine clinical management and clinical trials. As in-person services were severely limited, clinicians turned to remote assessments through telehealth to allow for continued care. Typically, disease-specific clinical outcome assessments (COAs) for neuromuscular disorders (NMD) are developed over many years through rigorous and iterative processes to fully understand their psychometric properties. While efforts were underway towards developing remote assessments for NMD before the pandemic, few if any were fully developed or validated. These included assessments of strength, respiratory function and patient-reported outcomes, as well as wearable technology and other devices to quantify physical activity and function. Without many choices, clinicians modified COAs for a virtual environment recognizing it was not yet known how they compared to standard in-person administration. Despite being able to quickly adapt to the demands of the COVID-19 pandemic, these experiences with remote assessments uncovered limitations and opportunities. It became clear that existing COAs required modifications for use in a virtual environment limiting the interpretation of the information gathered. Still, the opportunity for real-world evaluation and reduced patient burden were clear benefits to remote assessment and may provide a more robust understanding and characterization of disease impact in NMD. Hence, we propose a roadmap navigating an informed post-pandemic path toward development and implementation of safe and successful use of remote assessments for patients with NMD.
The emergence of molecular systems neuroscience
Authors: Shen Yang , Luchetti Alessandro , Fernandes Giselle , Do Heo Won , Silva Alcino J. 
Published: January 2022

AbstractSystems neuroscience is focused on how ensemble properties in the brain, such as the activity of neuronal circuits, gives rise to internal brain states and behavior. Many of the studies in this field have traditionally involved electrophysiological recordings and computational approaches that attempt to decode how the brain transforms inputs into functional outputs. More recently, systems neuroscience has received an infusion of approaches and techniques that allow the manipulation (e.g., optogenetics, chemogenetics) and imaging (e.g., two-photon imaging, head mounted fluorescent microscopes) of neurons, neurocircuits, their inputs and outputs. Here, we will review novel approaches that allow the manipulation and imaging of specific molecular mechanisms in specific cells (not just neurons), cell ensembles and brain regions. These molecular approaches, with the specificity and temporal resolution appropriate for systems studies, promise to infuse the field with novel ideas, emphases and directions, and are motivating the emergence of a molecularly oriented systems neuroscience, a new discipline that studies how the spatial and temporal patterns of molecular systems modulate circuits and brain networks, and consequently shape the properties of brain states and behavior.
Early, biomarker-guided steroid dosing in COVID-19 Pneumonia: a pilot randomized controlled trial
Authors: Odeyemi Yewande E. , Chalmers Sarah J. , Barreto Erin F. , Jentzer Jacob C. , Gajic Ognjen , Yadav Hemang 
Published: January 2022

AbstractClinicalTrials.gov identifier (NCT number): NCT03852537, Registered February 25, 2019.