bluuebunny/crossref_metadata_2025_split huggingface dataset:
Supraphysiologic doses of 17β-estradiol aggravate depression-like behaviors in ovariectomized mice possibly via regulating microglial responses and brain glycerophospholipid metabolism
Authors: Li Ming , Zhang Jing , Chen Wendi , Liu Shuang , Liu Xin , Ning Yunna , Cao Yongzhi , Zhao Yueran 
Published: September 2023

Abstract
Background
17β-Estradiol (E2) is generally considered neuroprotective in humans. However, the current clinical use of estrogen replacement therapy (ERT) is based on the physiological dose of E2 to treat menopausal syndrome and has limited therapeutic efficacy. The efficacy and potential toxicity of superphysiological doses of ERT for menopausal neurodegeneration are unknown.

Methods
In this study, we investigated the effect of E2 with a supraphysiologic dose (0.5 mg/kg, sE2) on the treatment of menopausal mouse models established by ovariectomy. We performed the open field, Y-maze spontaneous alternation, forced swim tests, and sucrose preference test to investigate behavioral alterations. Subsequently, the status of microglia and neurons was detected by immunohistochemistry, HE staining, and Nissl staining, respectively. Real-time PCR was used to detect neuroinflammatory cytokines in the hippocampus and cerebral cortex. Using mass spectrometry proteomics platform and LC–MS/ MS-based metabolomics platform, proteins and metabolites in brain tissues were extracted and analyzed. BV2 and HT22 cell lines and primary neurons and microglia were used to explore the underlying molecular mechanisms in vitro.

Results
sE2 aggravated depression-like behavior in ovariectomized mice, caused microglia response, and increased proinflammatory cytokines in the cerebral cortex and hippocampus, as well as neuronal damage and glycerophospholipid metabolism imbalance. Subsequently, we demonstrated that sE2 induced the pro-inflammatory phenotype of microglia through ERα/NF-κB signaling pathway and downregulated the expression of cannabinoid receptor 1 in neuronal cells, which were important in the pathogenesis of depression.

Conclusion
These data suggest that sE2 may be nonhelpful or even detrimental to menopause-related depression, at least partly, by regulating microglial responses and glycerophospholipid metabolism.
Antibody production and characterization of the nucleoprotein of sever fever with thrombocytopenia syndrome virus (SFTSV) for effective diagnosis of SFTSV
Authors: Lee Kyungha , Choi Min Ji , Cho Man-Ho , Choi Dong Ok , Bhoo Seong-Hee 
Published: September 2023

Abstract
Background
Severe fever with thrombocytopenia syndrome (SFTS) is an infectious disease caused by the Dabie bandavirus, [or SFTS virus (SFTSV)] that has become increasingly widespread since it was first reported in 2009. The SFTSV comprises three essential single-stranded RNA gene segments, with the S segment encoding the nucleocapsid (N) protein. Since the N protein is the most abundant and stable viral protein, it is a useful diagnostic marker of infection. Various SFTSV N-protein-based detection methods have been developed. However, given the limited research on antibodies of an SFTSV N-protein, here we report the characterization of the antibodies against SFTSV N protein especially their mapping results which is essential for more efficient and optimized detection of SFTSV.

Methods
To generate SFTSV-N-protein-specific monoclonal antibodies, recombinant full-length SFTSV N protein was expressed in E. coli, and the purified N protein was immunized to mice. The binding epitope positions of the antibodies generated were identified through binding-domain mapping. An antibody pair test using a lateral flow immunoassay (LFIA) was performed to identify effective diagnostic combinations of paired antibodies.

Results
Nine monoclonal antibodies specific for the SFTSV N protein were generated. Antibodies #3(B4E2) and #5(B4D9) were specific for sequential epitopes, while the remainder were specific for conformational epitopes. Antibody #4(C2G1) showed the highest affinity for the SFTSV N protein. The binding domain mapping results indicated the binding regions of the antibodies were divided into three groups. The antibody pair test demonstrated that #3(B4E2)/#4(C2G1) and #4(C2G1)/#5(B4D9) were effective antibody pairs for SFTSV diagnosis.

Conclusions
Effective virus detection requires at least two strong antibodies recognizing separate epitope binding sites of the virus antigen. Here, we generated SFTSV-N-protein-specific monoclonal antibodies and subsequently performed epitope mapping and an antibody pair test to enhance the diagnostic efficiency and accuracy of SFTSV. Confirmation of epitope mappings and their combination immune response to the N protein provide valuable information for effective detection of SFTSV as well as can respond actively to detect a variant SFTSV.
Asthma and COVID-19: a controversial relationship
Authors: Dounce-Cuevas Carlos A. , Flores-Flores Angélica , Bazán Mariana S. , Portales-Rivera Victor , Morelos-Ulíbarri Araceli A. , Bazán-Perkins Blanca 
Published: September 2023

AbstractSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection induces a spectrum of clinical manifestations that depend on the immune response of the patient, i.e., from an asymptomatic form to an inflammatory response with multiorgan deterioration. In some cases, severe cases of SARS-CoV-2 are characterized by an excessive, persistent release of inflammatory mediators known as a cytokine storm. This phenomenon arises from an ineffective T helper (Th)-1 response, which is unable to control the infection and leads to a reinforcement of innate immunity, causing tissue damage. The evolution of the disease produced by SARS-CoV2, known as COVID-19, has been of interest in several research fields. Asthma patients have been reported to present highly variable outcomes due to the heterogeneity of the disease. For example, the Th2 response in patients with allergic asthma is capable of decreasing Th1 activation in COVID-19, preventing the onset of a cytokine storm; additionally, IL-33 released by damaged epithelium in the context of COVID-19 potentiates either Th1 or T2-high responses, a process that contributes to poor outcomes. IL-13, a T2-high inflammatory cytokine, decreases the expression of angiotensin converting enzyme-2 (ACE2) receptor, hindering SARS-CoV-2 entry; finally, poor outcomes have been observed in COVID-19 patients with severe neutrophilic asthma. In other contexts, the COVID-19 lockdown has had interesting effects on asthma epidemiology. The incidence of asthma in the most populated states in Mexico, including Tamaulipas, which has the highest asthma incidence in the country, showed similar tendencies independent of how strict the lockdown measures were in each state. As described worldwide for various diseases, a decrease in asthma cases was observed during the COVID-19 lockdown. This decrease was associated with a drop in acute respiratory infection cases. The drop in cases of various diseases, such as diabetes, hypertension or depression, observed in 2020 was restored in 2022, but not for asthma and acute respiratory infections. There were slight increases in asthma cases when in-person classes resumed. In conclusion, although many factors were involved in asthma outcomes during the pandemic, it seems that acute respiratory infection is intimately linked to asthma cases. Social distancing during remote learning, particularly school lockdown, appears to be an important cause of the decrease in cases.
Perceived stress of mental demands at work, objective stress and resilience – an analysis of the LIFE-Adult-study
Authors: Jung Franziska U. , Pabst Alexander , Rodriguez Francisca S. , Luppa Melanie , Engel Christoph , Kirsten Toralf , Witte Veronica , Reyes Nigar , Loeffler Markus , Villringer Arno , Riedel-Heller Steffi G. 
Published: September 2023

Abstract
Background
So far, previous research suggests positive effects of mental demands at the workplace. However, it may depend on how stressfull these demands are perceived on an individual level.

Objective
The aim was to build on previous research by investigating how mental demands are related to stress, overload, and work discontent and whether this relationship is mediated by individuals resources, such as resilience.

Method
A sub-sample of the LIFE Adult Cohort (n = 480) was asked to answer questions on sociodemographic characteristics, objective stress (using the Trier Inventory of Chronic Stress (TICS)), and perceptions of stress with regard to verbal and executive mental demands at work.

Results
According to generalized linear regression models, higher verbal as well as executive mental demands were associated with higher levels of chronic stress, work overload and discontent. Higher levels of resilience were associated with lower levels of these outcomes. Analyses regarding interaction effects revealed that the interaction between resilience and perceived stress of verbal mental demands was significant only in terms of work overload.

Conclusion
Higher perceived stressfulness of mental demands was associated with higher chronic stress, work overload and work discontent. Therefore, mental demands should be targeted by occupational interventions that aim to improve job conditions and employees‘ overall well-being. Besides resilience, other potential influencers or personal resources should be focused on in future studies to develop interventions.
Beyond artificial academic debates: for a diverse, inclusive, and impactful ethnobiology and ethnomedicine
Authors: Reyes-García Victoria 
Published: September 2023

AbstractIn answer to the question “Should ethnobiology and ethnomedicine more decisively foster hypothesis-driven forefront research able to turn findings into policy and abandon more classical folkloric studies?”, in this essay I argue that a major strength of ethnobiology and ethnomedicine is their ability to bridge theories and methods from the natural sciences, the social sciences, and the humanities. Hypothesis-driven research is a powerful way to structure thinking that can lead to forefront research findings. But hypothesis-driven research is not the only way to structure thinking and is not a necessary condition to impact policymaking. To increase policy impact, ethnobiology and ethnomedicine should continue nurturing a mixture of complementary methods and inclusive approaches as fragmentation through opposing different approaches might weaken the discipline. Moreover, with the aim to play a fundamental role in building bridges between different knowledge systems and co-producing solutions towards sustainability, the discipline could benefit from enlarging its epistemological grounds through more collaborative research. Ethnobiologists' research findings, hypothesis-driven, descriptive, or co-constructed can become leverage points to transform knowledge into actionable outcomes in different levels of decision-making.
Ajugol's upregulation of TFEB-mediated autophagy alleviates endoplasmic reticulum stress in chondrocytes and retards osteoarthritis progression in a mouse model
Authors: Wu Jingtao , Yu Heng , Jin Yangcan , Wang Jingquan , Zhou Liwen , Cheng Teng , Zhang Zhao , Lin Binghao , Miao Jiansen , Lin Zhongke 
Published: September 2023

AbstractBackgroundOsteoarthritis (OA), a degenerative disease with a high global prevalence, is characterized by the degradation of the extracellular matrix (ECM) and the apoptosis of chondrocytes. Ajugol, a extract derived from the herb Rehmannia glutinosa, has not yet been investigated for its potential in modulating the development of OA.MethodsWe employed techniques such as western blotting, immunofluorescence, immunohistochemistry, X-ray imaging, HE staining, and SO staining to provide biological evidence supporting the role of Ajugol as a potential therapeutic agent for modulating OA. Furthermore, in an in vivo experiment, intra-peritoneal injection of 50 mg/kg Ajugol effectively mitigated the progression of OA following destabilization of the medial meniscus (DMM) surgery.ResultsOur findings revealed that treatment with 50 μM Ajugol activated TFEB-mediated autophagy, alleviating ER stress-induced chondrocyte apoptosis and ECM degradation caused by TBHP. Furthermore, in an in vivo experiment, intra-peritoneal injection of 50 mg/kg Ajugol effectively mitigated the progression of OA following destabilization of the medial meniscus (DMM) surgery.ConclusionThese results provide compelling biological evidence supporting the role of Ajugol as a potential therapeutic agent for modulating OA by activating autophagy and attenuating ER stress-induced cell death and ECM degradation. The promising in vivo results further suggest the potential of Ajugol as a treatment strategy for OA progression.
COVID-19 vaccination is associated with enhanced efficacy of anti-PD-(L)1 immunotherapy in advanced NSCLC patients: a real-world study
Authors: Qian Yunfei , Zhu Zhuxian , Mo Yin-Yuan , Zhang Ziqiang 
Published: September 2023

Abstract
Background
Coronavirus disease 2019 (COVID-19) vaccine has played a major role in ending the pandemic. However, little is known about the influence of COVID-19 vaccine on the efficacy of immunotherapy in patients with non-small cell lung cancer (NSCLC).

Objectives
The goal of this study is to explore whether COVID-19 vaccine impacts the efficacy of immune checkpoint inhibitors (ICIs) in NSCLC patients.

Methods
We retrospectively analyzed the survival data of ICI-treated 104 patients with stage III–IV NSCLC, who either received COVID-19 vaccination (n = 25) or no vaccination (n = 79). The potential risk factors, in particular roles of COVID-19 vaccination in the efficacy of ICIs in these patients, were evaluated.

Results
Our results showed significantly improved ORR (28.0% vs. 11.39%, p = 0.05) and DCR (88.0% vs. 54.43%, p = 0.005) in the COVID-19 vaccinated group compared with the non-vaccinated group. Regarding the long-term survival benefits, COVID-19 vaccine showed profound influence both on the PFS (HR = 0.16, p = 0.021) and OS (HR = 0.168, p = 0.019) in patients with NSCLC under ICIs treatment. The PFS (p < 0.001) or OS (p < 0.001) was significantly improved in the COVID-19 vaccinated group, compared with the non-vaccinated group. Moreover, CD4 T cell (p = 0.047) level was higher in the COVID-19 vaccinated group than in the non-vaccinated group.

Conclusions
COVID-19 vaccination enhances anti-PD-1 immunotherapy efficacy in patients with stage III–IV NSCLC, suggesting that COVID-19 vaccination may provide additional benefit to NSCLC patients.
Associations over the COVID-19 pandemic period and the mental health and substance use of youth not in employment, education or training in Ontario, Canada: a longitudinal, cohort study
Authors: Quinlan-Davidson Meaghen , Shan Di , Courtney Darren , Barbic Skye , Cleverley Kristin , Hawke Lisa D. , Ma Clement , Prebeg Matthew , Relihan Jacqueline , Szatmari Peter , Henderson J. L. 
Published: September 2023

Abstract
Background
The economic shutdown and school closures associated with the COVID-19 pandemic have negatively influenced many young people’s educational and training opportunities, leading to an increase in youth not in education, employment, or training (NEET) globally and in Canada. NEET youth have a greater vulnerability to mental health and substance use problems, compared to their counterparts who are in school and/or employed. There is limited evidence on the association between COVID-19 and NEET youth. The objectives of this exploratory study included investigating: longitudinal associations between the COVID-19 pandemic and the mental health and substance use (MHSU) of NEET youth; and MHSU among subgroups of NEET and non-NEET youth.

Methods
618 youth (14–28 years old) participated in this longitudinal, cohort study. Youth were recruited from four pre-existing studies at the Centre for Addiction and Mental Health. Data on MHSU were collected across 11 time points during the COVID-19 pandemic (April 2020-August 2022). MHSU were measured using the CoRonavIruS Health Impact Survey Youth Self-Report, the Global Appraisal of Individual Needs Short Screener, and the PTSD Checklist for DSM-5. Linear Mixed Models and Generalized Estimating Equations were used to analyze associations of NEET status and time on mental health and substance use. Exploratory analyses were conducted to investigate interactions between sociodemographic characteristics and NEET status and time.

Results
At baseline, NEET youth were significantly more likely to screen positive for an internalizing disorder compared to non-NEET youth (OR = 1.92; 95%CI=[1.26–2.91] p = 0.002). No significant differences were found between youth with, and without, NEET in MHSU symptoms across the study time frame. Youth who had significantly higher odds of screening positive for an internalizing disorder included younger youth (OR = 1.06, 95%CI=[1.00-1.11]); youth who identify as Trans, non-binary or gender diverse (OR = 8.33, 95%CI=[4.17–16.17]); and those living in urban areas (OR = 1.35, 95%CI=[1.03–1.76]), compared to their counterparts. Youth who identify as White had significantly higher odds of screening positive for substance use problems (OR = 2.38, 95%CI=[1.72–3.23]) compared to racialized youth.

Conclusions
Our findings indicate that sociodemographic factors such as age, gender identity, ethnicity and area of residence impacted youth MHSU symptoms over the course of the study and during the pandemic. Overall, NEET status was not consistently associated with MHSU symptoms over and above these factors. The study contributes to evidence on MHSU symptoms of NEET youth.
Evaluating the psychometric properties of the Chinese Depression Anxiety Stress Scale for Youth (DASS-Y) and DASS-21
Authors: Cao Cui-hong , Liao Xiao-ling , Gamble Jeffrey H. , Li Ling-ling , Jiang Xing-Yong , Li Xu-Dong , Griffiths Mark D. , Chen I-Hua , Lin Chung-Ying 
Published: September 2023

Abstract
Background
In recognizing the need for a reliable and valid instrument to assess psychological distress among children and adolescents, the present study translated the newly developed Depression Anxiety Stress Scale for Youth (DASS-Y) into Chinese, while also comparing its psychometric properties with those of the well-established DASS-21 within a primary and middle school demographic.

Methods
Utilizing a combination of convenience sampling and purposive sampling, a cohort comprising 1,507 primary and 1,131 middle school students was recruited. Rasch analysis, confirmatory factor analysis (CFA), and structural equation modeling (SEM) were used in the data analysis.

Results
Significant differences were observed between the DASS-Y and the DASS-21, notably within the anxiety subscale. The proportions of individuals with clinical mood disorders identified by the two scales demonstrated a significant disparity. Both scales, following an adjustment of responses, exhibited satisfactory internal consistency and convergent validity, with the acceptance of a three-factor structure. Furthermore, the DASS-Y showed superior discriminant validity relative to the DASS-21, providing more compelling evidence regarding concurrent validity.

Conclusion
Overall, the Chinese version of the DASS-Y demonstrated superior robustness to the DASS-21 in terms of psychometric properties. The findings provide initial evidence for the psychometric properties of the DASS-Y from another culture.
Effect of surgical approach on the treatment of Morton's neuroma: a systematic review and meta‐analysis
Authors: Zhang Jiayao , Li Jing , Cai Wufeng , Zheng Kaiwen , Huang Xihao , Rong Xin , Li Qi 
Published: September 2023

AbstractBackgroundSurgical resection of Morton's neuroma includes dorsal and plantar approaches. However, there is no consensus on the choice of approach in clinic. The purpose of this study was to conduct a systematic review and meta‐analysis to compare the surgical results of dorsal and plantar approaches.MethodsThe literatures of PubMed, Cochrane library, Embase and Web of Science were searched on April 26th, 2023. A systematic review was performed using the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis guidelines. The data were extracted after screening the literature and evaluating the quality of the methodology included in the study. The RevMan5.4 software was used to analyze and calculate the OR value and 95% confidence interval.ResultsA total of 7 randomized controlled trials and comparative studies were published, of which only 5 were included. There were 158 feet via plantar approach (plantar group, PG) and 189 via dorsal approach (dorsal group, DG). There was no significant difference between PG and DG in overall adverse events, sensory problems, incision infection and deep vein thrombosis (p > 0.05). In terms of scar problems, PG showed more than DG (OR, 2.90[95%CI, 1.40 to 5.98]; p = 0.004). Other outcome indicators such as visual analogue scale (VAS) scores and American Orthopedic Foot and Ankle Society (AOFAS) scores were difficult to be included in the comparison.ConclusionsBased on the relatively low quality and small amount of available evidence, the meta‐analysis conducted produces a hypothesis that the frequency of adverse events in surgical treatment of Morton's neuroma, dorsal approach and plantar approach may be the same, but the types are different. More high‐level evidence is needed to further verify this hypothesis.
Out-of-hospital cardiac arrest in children: an epidemiological study based on the German Resuscitation Registry identifying modifiable factors for return of spontaneous circulation
Authors: Katzenschlager Stephan , Kelpanides Inga K. , Ristau Patrick , Huck Matthias , Seewald Stephan , Brenner Sebastian , Hoffmann Florian , Wnent Jan , Kramer-Johansen Jo , Tjelmeland Ingvild B. M. , Weigand Markus A. , Gräsner Jan-Thorsten , Popp Erik 
Published: September 2023

Abstract
Aim
This work provides an epidemiological overview of out-of-hospital cardiac arrest (OHCA) in children in Germany between 2007 and 2021. We wanted to identify modifiable factors associated with survival.

Methods
Data from the German Resuscitation Registry (GRR) were used, and we included patients registered between 1st January 2007 and 31st December 2021. We included children aged between > 7 days and 17 years, where cardiopulmonary resuscitation (CPR) was started, and treatment was continued by emergency medical services (EMS). Incidences and descriptive analyses are presented for the overall cohort and each age group. Multivariate binary logistic regression was performed on the whole cohort to determine the influence of (1) CPR with/without ventilation started by bystander, (2) OHCA witnessed status and (3) night-time on the outcome hospital admission with return of spontaneous circulation (ROSC).

Results
OHCA in children aged < 1 year had the highest incidence of the same age group, with 23.42 per 100 000. Overall, hypoxia was the leading presumed cause of OHCA, whereas trauma and drowning accounted for a high proportion in children aged > 1 year. Bystander-witnessed OHCA and bystander CPR rate were highest in children aged 1–4 years, with 43.9% and 62.3%, respectively. In reference to EMS-started CPR, bystander CPR with ventilation were associated with an increased odds ratio for ROSC at hospital admission after adjusting for age, sex, year of OHCA and location of OHCA.

Conclusion
This study provides an epidemiological overview of OHCA in children in Germany and identifies bystander CPR with ventilation as one primary factor for survival.
Trial registrations German Clinical Trial Register: DRKS00030989, December 28th 2022.

Graphical Abstract