bluuebunny/crossref_metadata_2025_split huggingface dataset:
Breaking down barriers: comprehensive functional analysis of the Aspergillus niger chitin synthase repertoire
Authors: Barthel Lars , Cairns Timothy , Duda Sven , Müller Henri , Dobbert Birgit , Jung Sascha , Briesen Heiko , Meyer Vera 
Published: March 2024

Abstract
Background
Members of the fungal kingdom are heterotrophic eukaryotes encased in a chitin containing cell wall. This polymer is vital for cell wall stiffness and, ultimately, cell shape. Most fungal genomes contain numerous putative chitin synthase encoding genes. However, systematic functional analysis of the full chitin synthase catalogue in a given species is rare. This greatly limits fundamental understanding and potential applications of manipulating chitin synthesis across the fungal kingdom.

Results
In this study, we conducted in silico profiling and subsequently deleted all predicted chitin synthase encoding genes in the multipurpose cell factory Aspergillus niger. Phylogenetic analysis suggested nine chitin synthases evolved as three distinct groups. Transcript profiling and co-expression network construction revealed remarkably independent expression, strongly supporting specific role(s) for the respective chitin synthases. Deletion mutants confirmed all genes were dispensable for germination, yet impacted colony spore titres, chitin content at hyphal septa, and internal architecture of submerged fungal pellets. We were also able to assign specific roles to individual chitin synthases, including those impacting colony radial growth rates (ChsE, ChsF), lateral cell wall chitin content (CsmA), chemical genetic interactions with a secreted antifungal protein (CsmA, CsmB, ChsE, ChsF), resistance to therapeutics (ChsE), and those that modulated pellet diameter in liquid culture (ChsA, ChsB). From an applied perspective, we show chsF deletion increases total protein in culture supernatant over threefold compared to the control strain, indicating engineering filamentous fungal chitin content is a high priority yet underexplored strategy for strain optimization.

Conclusion
This study has conducted extensive analysis for the full chitin synthase encoding gene repertoire of A. niger. For the first time we reveal both redundant and non-redundant functional roles of chitin synthases in this fungus. Our data shed light on the complex, multifaceted, and dynamic role of chitin in fungal growth, morphology, survival, and secretion, thus improving fundamental understanding and opening new avenues for biotechnological applications in fungi.
Targeting vulnerable microcircuits in the ventral hippocampus of male transgenic mice to rescue Alzheimer-like social memory loss
Authors: Lei Hui-Yang , Pi Gui-Lin , He Ting , Xiong Rui , Lv Jing-Ru , Liu Jia-Le , Wu Dong-Qin , Li Meng-Zhu , Shi Kun , Li Shi-Hong , Yu Na-Na , Gao Yang , Yu Hui-Ling , Wei Lin-Yu , Wang Xin , Zhou Qiu-Zhi , Zou Pei-Lin , Zhou Jia-Yang , Liu Ying-Zhou , Shen Nai-Ting , Yang Jie , Ke Dan , Wang Qun , Liu Gong-Ping , Yang Xi-Fei , Wang Jian-Zhi , Yang Ying 
Published: March 2024

Abstract
Background
Episodic memory loss is a prominent clinical manifestation of Alzheimer’s disease (AD), which is closely related to tau pathology and hippocampal impairment. Due to the heterogeneity of brain neurons, the specific roles of different brain neurons in terms of their sensitivity to tau accumulation and their contribution to AD-like social memory loss remain unclear. Therefore, further investigation is necessary.

Methods
We investigated the effects of AD-like tau pathology by Tandem mass tag proteomic and phosphoproteomic analysis, social behavioural tests, hippocampal electrophysiology, immunofluorescence staining and in vivo optical fibre recording of GCaMP6f and iGABASnFR. Additionally, we utilized optogenetics and administered ursolic acid (UA) via oral gavage to examine the effects of these agents on social memory in mice.

Results
The results of proteomic and phosphoproteomic analyses revealed the characteristics of ventral hippocampal CA1 (vCA1) under both physiological conditions and AD-like tau pathology. As tau progressively accumulated, vCA1, especially its excitatory and parvalbumin (PV) neurons, were fully filled with mislocated and phosphorylated tau (p-Tau). This finding was not observed for dorsal hippocampal CA1 (dCA1). The overexpression of human tau (hTau) in excitatory and PV neurons mimicked AD-like tau accumulation, significantly inhibited neuronal excitability and suppressed distinct discrimination-associated firings of these neurons within vCA1. Photoactivating excitatory and PV neurons in vCA1 at specific rhythms and time windows efficiently ameliorated tau-impaired social memory. Notably, 1 month of UA administration efficiently decreased tau accumulation via autophagy in a transcription factor EB (TFEB)-dependent manner and restored the vCA1 microcircuit to ameliorate tau-impaired social memory.

Conclusion
This study elucidated distinct protein and phosphoprotein networks between dCA1 and vCA1 and highlighted the susceptibility of the vCA1 microcircuit to AD-like tau accumulation. Notably, our novel findings regarding the efficacy of UA in reducing tau load and targeting the vCA1 microcircuit may provide a promising strategy for treating AD in the future.
Development of a quality of work life scale for Japanese community pharmacists: a questionnaire survey mostly in large companies
Authors: Kato Yuta , Sekiya Takashi , Ishii Ryo , Hirako Yoji , Satoh Hiroki , Kimura Hiromichi 
Published: March 2024

Abstract
Background
Human resource management may become complex for community pharmacists owing to recent changes in work volume and content. Few studies have examined job satisfaction, well-being, and quality of work life (QWL) among community pharmacists in Japan. This study focused on QWL, a more comprehensive concept than job satisfaction, and aimed to develop the QWL questionnaire for Japanese community pharmacists (the QWLQ for JCP) and assess its reliability and validity.

Methods
A questionnaire survey was conducted among 2027 pharmacists who worked in pharmacies with the cooperation of 20 corporations running pharmacies. Collected data were subjected to principal component factor analysis with Promax rotation via SPSS Windows version 28.

Results
The factor analysis used data from 1966 pharmacists. In total, five significant components, which formed the basis of the QWLQ for JCP, were identified. These included “Influence of work on mind and body,” “Relationships with colleagues,” “Relationship with the boss,” “Meaning of existence in the workplace,” and “Pride in work.” Cronbach’s alpha, which expressed reliability, ranged from 0.585 to 0.854 for all the subscales.

Conclusion
The QWLQ for the JCP significantly explained the concept of QWL, which indicated that its validity was sufficient.
"An L2 Education without Love is not Education at All": a phenomenographic study of undergraduate EFL students’ perceptions of pedagogical love
Authors: Ghiasvand Farhad , Sharifpour Pardis 
Published: March 2024

AbstractThe role of pedagogical love in second language (L2) education has long remained under-explored due to dogmatic religious and cultural beliefs. There is insufficient scholarship on this construct at undergraduate levels. To bridge this gap, the present study employed a phenomenographic design to uncover Iranian undergraduate students’ perceptions of pedagogical love and its features, realizations, and determinant factors. It invited 22 undergraduate L2 learners to attend a semi-structured interview and complete a narrative frame. The results of content and thematic analysis attained through MAXQDA software (v. 20) revealed that the participants had different perceptions of pedagogical love. They considered it as a non-romantic intimacy and respect, deep care for students and their emotions, and pure love based on mutual trust. Furthermore, it was found that pedagogical love is essential for L2 education as characterized by a mutual trust and respect, kindness, care, bonding, intimacy, and forgiveness. Regarding its realizations, the results demonstrated that pedagogical love shows itself through intimacy, classroom engagement/participation, confidence, academic performance, and mutual care, respect, and responsibility. Moreover, it was identified that teachers’ emotional literacy, teachers’ pedagogical expertise, and positive classroom rapport facilitated the implementation of loving pedagogy at undergraduate level. Finally, the findings indicated that loving pedagogy practice was mostly precluded by strict religious beliefs, stigmatizing socio-cultural norms, emotion expression, fear, and traditional educational systems. Implications for L2 teachers and educators are discussed to augment their understanding of pedagogical love, as an opportunity to grasp the emotional side of language education.
Gene editing technology to improve antitumor T-cell functions in adoptive immunotherapy
Authors: Ito Yusuke , Inoue Satoshi , Kagoya Yuki 
Published: March 2024

AbstractAdoptive immunotherapy, in which tumor-reactive T cells are prepared in vitro for adoptive transfer to the patient, can induce an objective clinical response in specific types of cancer. In particular, chimeric antigen receptor (CAR)-redirected T-cell therapy has shown robust responses in hematologic malignancies. However, its efficacy against most of the other tumors is still insufficient, which remains an unmet medical need. Accumulating evidence suggests that modifying specific genes can enhance antitumor T-cell properties. Epigenetic factors have been particularly implicated in the remodeling of T-cell functions, including changes to dysfunctional states such as terminal differentiation and exhaustion. Genetic ablation of key epigenetic molecules prevents the dysfunctional reprogramming of T cells and preserves their functional properties.Clustered, regularly interspaced, short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas)-based gene editing is a valuable tool to enable efficient and specific gene editing in cultured T cells. A number of studies have already identified promising targets to improve the therapeutic efficacy of CAR-T cells using genome-wide or focused CRISPR screening. In this review, we will present recent representative findings on molecular insights into T-cell dysfunction and how genetic modification contributes to overcoming it. We will also discuss several technical advances to achieve efficient gene modification using the CRISPR and other novel platforms.
Neuroprotective effect of bromelain on BDNF-TRKB signalling pathway in chronic unpredictable stress-induced depression model
Authors: Parasuraman Rajeshwari , Jayamurali Dheepthi , Manoharan Nivedita , Govindarajalu Sathya Narayanan 
Published: March 2024

Abstract
Background
Bromelain is a mixture of protease enzyme extract from the fruit or stem of the pineapple plant. It has a wide range of biological actions, and it is most commonly used as an anti-inflammatory agent. This study was designed to investigate the antidepressant effect of bromelain on chronic unpredictable stress (CUS)-induced depression in rat models by targeting various molecular mechanisms.

Result
We studied the in silico analysis of the antidepressant potential of bromelain by docking with various proteins involved in the pathophysiology of depression. As a result of in silico studies, bromelain showed good binding energy with IL1β, 5-HT, BDNF, CREB, and TrkB. The mRNA expression of BDNF, TrkB, AKT, ERK, and IL-1β was studied by qRT-PCR. Gene expression studies showed a significant decrease in BDNF, TrkB, AKT, and ERK in chronic unpredictable stress, whereas there was a significant increase in the case of the bromelain- and fluoxetine-treated group. Since neuroinflammation is also one of the major concerns in the pathophysiology of depression, pro-inflammatory cytokines were also studied along with apoptotic markers using ELISA. ELISA results showed a significant increase in inflammatory cytokines in CUS, and it was significantly decreased in the case of the bromelain- and fluoxetine-treated group. Similarly, there was an increased concentration of pro-apoptotic protein in the CUS group, whereas it was decreased in the bromelain and fluoxetine groups.

Conclusions
From the results, it is clear that bromelain exerts an antidepressive effect by preventing neuroinflammation and neurodegeneration and by enhancing neurogenesis and neuroplasticity.

Graphical abstract
Loneliness in adolescence and prescription of psychotropic drugs in adulthood: 23-year longitudinal population-based and registry study
Authors: Rodríguez-Cano Rubén , Lotre Karianne , von Soest Tilmann , Rognli Eline Borger , Bramness Jørgen Gustav 
Published: March 2024

Background
The role of adolescent loneliness in adult mental health and prescriptions of psychotropic drugs remains underexplored.

Aims
We aim to determine whether (a) experiencing loneliness in adolescence and (b) changes in loneliness from adolescence to adulthood are prospectively associated with prescriptions for a variety of psychotropic drugs in adulthood.

Method
We used data from a Norwegian population-based sample with 2602 participants, collected across four waves between 1992 and 2006. Loneliness was assessed at each wave, with survey data linked to medicinal drug prescription records from the Norwegian Prescription Database. We identified prescription histories of antipsychotics, mood stabilisers, antidepressants and benzodiazepines from 2007 to 2015, for each participant. We use latent growth curve analyses to model the relationship of adolescent loneliness and loneliness change from adolescence to adulthood, with subsequent psychotropic drugs prescription.

Results
Adolescents with heightened loneliness, and adolescents whose loneliness increased into young adulthood, had a greater likelihood of being prescribed antipsychotics, mood stabilisers and antidepressants in adulthood. These associations remained significant after adjustment for confounders such as sociodemographic characteristics, conduct problems, substance use and mental health problems.

Conclusions
Loneliness in adolescence and its adverse development over a span of 15 years was linked to higher risk of receiving prescriptions for antipsychotics, mood stabilisers and antidepressants later in life. The findings may indicate that loneliness increases the risk for developing psychotic disorders, bipolar disorders and major depression.
The Effects of Peri-Operative Adverse Events on Clinical and Patient-Reported Outcomes After Surgery for Degenerative Cervical Myelopathy: An Observational Cohort Study from the Canadian Spine Outcomes and Research Network
Authors: Malhotra Armaan K. , Evaniew Nathan , Dea Nicolas , Fisher Charles G. , Street John T. , Cadotte David W. , Jacobs W. Bradley , Thomas Kenneth C. , Attabib Najmedden , Manson Neil , Hall Hamilton , Bailey Christopher S. , Nataraj Andrew , Phan Philippe , Rampersaud Y Raja , Paquet Jerome , Weber Michael H. , Christie Sean D. , McIntosh Greg , Wilson Jefferson R. 
Published: March 2024

BACKGROUND AND OBJECTIVES:
There is a lack of data examining the effects of perioperative adverse events (AEs) on long-term outcomes for patients undergoing surgery for degenerative cervical myelopathy. We aimed to investigate associations between the occurrence of perioperative AEs and coprimary outcomes: (1) modified Japanese Orthopaedic Association (mJOA) score and (2) Neck Disability Index (NDI) score.

METHODS:
We analyzed data from 800 patients prospectively enrolled in the Canadian Spine Outcomes and Research Network multicenter observational study. The Spine AEs Severity system was used to collect intraoperative and postoperative AEs. Patients were assessed at up to 2 years after surgery using the NDI and the mJOA scale. We used a linear mixed-effect regression to assess the influence of AEs on longitudinal outcome measures as well as multivariable logistic regression to assess factors associated with meeting minimal clinically important difference (MCID) thresholds at 1 year.

RESULTS:
There were 167 (20.9%) patients with minor AEs and 36 (4.5%) patients with major AEs. The occurrence of major AEs was associated with an average increase in NDI of 6.8 points (95% CI: 1.1-12.4, P = .019) and reduction of 1.5 points for mJOA scores (95% CI: −2.3 to −0.8, P < .001) up to 2 years after surgery. Occurrence of major AEs reduced the odds of patients achieving MCID targets at 1 year after surgery for mJOA (odds ratio 0.23, 95% CI: 0.086-0.53, P = .001) and for NDI (odds ratio 0.34, 95% CI: 0.11-0.84, P = .032).

CONCLUSION:
Major AEs were associated with reduced functional gains and worse recovery trajectories for patients undergoing surgery for degenerative cervical myelopathy. Occurrence of major AEs reduced the probability of achieving mJOA and NDI MCID thresholds at 1 year. Both minor and major AEs significantly increased health resource utilization by reducing the proportion of discharges home and increasing length of stay.
Manipulation of the nuclear envelope-associated protein SLAP during mammalian brain development affects cortical lamination and exploratory behavior
Authors: Mestres Ivan , Atabay Azra , Escolano Joan-Carles , Arndt Solveig , Schmidtke Klara , Einsiedel Maximilian , Patsonis Melina , Bolaños-Castro Lizbeth Airais , Yun Maximina , Bernhardt Nadine , Taubenberger Anna , Calegari Federico 
Published: March 2024

ABSTRACT
Here, we report the first characterization of the effects resulting from the manipulation of Soluble-Lamin Associated Protein (SLAP) expression during mammalian brain development. We found that SLAP localizes to the nuclear envelope and when overexpressed causes changes in nuclear morphology and lengthening of mitosis. SLAP overexpression in apical progenitors of the developing mouse brain altered asymmetric cell division, neurogenic commitment and neuronal migration ultimately resulting in unbalance in the proportion of upper, relative to deeper, neuronal layers. Several of these effects were also recapitulated upon Cas9-mediated knockdown. Ultimately, SLAP overexpression during development resulted in a reduction in subcortical projections of young mice and, notably, reduced their exploratory behavior. Our study shows the potential relevance of the previously uncharacterized nuclear envelope protein SLAP in neurodevelopmental disorders.
Failures in Forecasting: An Experiment on Interpersonal Projection Bias
Authors: Bushong Benjamin , Gagnon-Bartsch Tristan 
Published: March 2024

Using a real-effort experiment, we show that people project their current tastes onto others when forecasting others’ behavior, even when their tastes are exogenously manipulated and transparently different. In the first part of our experiment, “workers” stated their willingness to continue working on a tedious task. We varied how many initial tasks workers completed before eliciting their willingness to work (WTW); some were relatively fresh when stating their WTW, whereas others were relatively tired. Later, a separate group of “predictors”—who also worked on the task—guessed the WTW of workers in each state. We find: (i) tired workers were less willing to work than fresh workers; (ii) predictors (in aggregate) accurately guessed the WTW of workers when they were in the same state as the workers about whom they were predicting; but (iii) when fresh predictors were guessing about tired workers, they substantially overestimated their WTW; and (iv) when tired predictors were guessing about fresh workers, they underestimated their WTW. Using an additional treatment, we find that workers also mispredicted their own future WTW, and we compare the magnitudes of intrapersonal and interpersonal projection bias. This paper was accepted by Axel Ockenfels, behavioral economics and decision analysis. Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2022.00655 .
Safety and effectiveness of butorphanol in epidural labor analgesia: A protocol for a systematic review and meta-analysis
Authors: Tang Guan-Cheng , He Man , Huang Zhen-Zhao , Cheng Yan 
Published: March 2024

BACKGROUND
Epidural analgesia is the most effective analgesic method during labor. Butorphanol administered epidurally has been shown to be a successful analgesic method during labor. However, no comprehensive study has examined the safety and efficacy of using butorphanol as an epidural analgesic during labor.
AIM
To assess butorphanol's safety and efficacy for epidural labor analgesia.
METHODS
The PubMed, Cochrane Library, EMBASE, Web of Science, China National Knowledge Infrastructure, and Google Scholar databases will be searched from inception. Other types of literature, such as conference abstracts and references to pertinent reviews, will also be reviewed. We will include randomized controlled trials comparing butorphanol with other opioids combined with local anesthetics for epidural analgesia during labor. There will be no language restrictions. The primary outcomes will include the visual analog scale score for the first stage of labor, fetal effects, and Apgar score. Two independent reviewers will evaluate the full texts, extract data, and assess the risk of bias. Publication bias will be evaluated using Egger's or Begg's tests as well as visual analysis of a funnel plot, and heterogeneity will be evaluated using the Cochran Q test, P values, and I 2 values. Meta-analysis, subgroup analysis, and sensitivity analysis will be performed using RevMan software version 5.4. This protocol was developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Protocols statement, and the PRISMA statement will be used for the systematic review.
RESULTS
This study provides reliable information regarding the safety and efficacy of using butorphanol as an epidural analgesic during labor.
CONCLUSION
To support clinical practice and development, this study provides evidence-based findings regarding the safety and efficacy of using butorphanol as an epidural analgesic during labor.