bluuebunny/crossref_metadata_2025_split huggingface dataset:
Juvenile hormone III induction reveals key genes in general metabolism, pheromone biosynthesis, and detoxification in Eurasian spruce bark beetle
Authors: Ramakrishnan Rajarajan , Roy Amit , Hradecký Jaromír , Kai Marco , Harant Karel , Svatoš Aleš , Jirošová Anna 
Published: January 2024

IntroductionIn recent years, bark beetle Ips typographus, has caused extensive damage to European Norway spruce forests through widespread outbreaks. This pest employs pheromone-assisted aggregation to overcome tree defense, resulting in mass attacks on host spruce. Many morphological and behavioral processes in I. typographus are under the regulation of juvenile hormone III (JH III), including the biosynthesis of aggregation pheromones and associated detoxification monoterpene conjugates.Objectives and MethodsIn this study, we topically applied juvenile hormone III (JH III) and performed metabolomics, transcriptomics, and proteomics in I. typographus both sexes, with focused aims; 1. Highlight the JH III-regulated metabolic processes; 2. Identify pheromone biosynthesis-linked genes; and 3. Investigate JH III’s impact on detoxification conjugates linked to pheromonal components.ResultsNumerous gene families were enriched after JH III treatment, including genes associated with catalytic and oxidoreductase activity, esterases, phosphatases, and membrane transporters. Sex-specific enrichments for reproduction-related and detoxification genes in females and metabolic regulation genes in males were observed. On the protein level were enriched metal ion binding and transferase enzymes in male beetles. After JHIII treatment, mevalonate pathway genes, including terminal isoprenyl diphosphate synthase (IPDS), were exclusively 35- folds upregulated in males, providing evidence of de novo biosynthesis of pheromone components 2-methyl-3-buten-2-ol and ipsdienol. In addition, cytochrome P450 genes likely involved in the biosynthesis of cis/trans-verbenol, detoxification, and formation of ipsdienol, were 3-fold upregulated in the male gut. The increase in gene expression correlated with the heightened production of the respective metabolites. Detoxification conjugates, verbenyl oleate in the beetle fat body and verbenyl diglycosides in the gut, were induced by JHIII application, which confirms the hormone regulation of their formation. The JH III induction also increased the gene contigs esterase and glycosyl hydrolase up to proteins from male gut tissue. The esterase was proposed to release pheromone cis-verbenol in adult males by breaking down verbenyl oleate. The correlating analyses confirmed a reduction in the abundance of verbenyl oleate in the induced male beetle.ConclusionThe data provide evidence of JH III’s regulatory role in the expression of genes and enzymes related to fundamental beetle metabolism, pheromone biosynthesis, and detoxification in Ips typographus.
Hereditary deafness carrier screening in 9,993 Chinese individuals
Authors: Liu Yanqiu , Wang Lei , Yuan Lanlai , Li Yaqing , Chen Zhengshi , Yang Bicheng , Wang Daqing , Sun Yu 
Published: January 2024

Background: Preconception or prenatal carrier screening plays an important role in reproductive decision-making, but current research on hereditary deafness is limited. This study aimed to investigate the carrier frequencies of common deafness genes in the Chinese population who underwent carrier screening and to follow up on pregnancy outcomes in high-chance couples.Methods: Individual females or couples in preconception or early pregnancy were recruited from two hospitals in China. Carrier screening for common deafness genes in the Chinese population, including the GJB2 and SLC26A4 genes, was performed using next-generation sequencing technology. Genetic counseling was provided to subjects before and after testing.Results: Of the 9,993 subjects screened, the carrier rate was 2.86% for the GJB2 gene and 2.63% for the SLC26A4 gene. The variant with the highest carrier frequency in GJB2 was c.235delC (1.89%), and c.919–2A&gt;G (1.08%) in SLC26A4. Of the six high-chance couples, four made alternative reproductive decisions (three with prenatal diagnosis and one with preimplantation genetic testing), with consequent termination of the birth of two affected fetuses.Conclusion: These findings confirmed the clinical utility of preconception or prenatal carrier screening for hereditary deafness.
Age-related exacerbation of lung damage after trauma is associated with increased expression of inflammasome components
Authors: Zhou Yuzhuo , Meng Fanshuai , Köhler Kernt , Bülow Jasmin Maria , Wagner Alessa , Neunaber Claudia , Bundkirchen Katrin , Relja Borna 
Published: January 2024

BackgroundTrauma, a significant global cause of mortality and disability, often leads to fractures and hemorrhagic shock, initiating an exaggerated inflammatory response, which harms distant organs, particularly the lungs. Elderly individuals are more vulnerable to immune dysregulation post-trauma, leading to heightened organ damage, infections, and poor health outcomes. This study investigates the role of NF-κB and inflammasomes in lung damage among aged mice post-trauma.MethodsTwelve male C57BL/6J mice underwent hemorrhagic shock and a femoral fracture (osteotomy) with external fixation (Fx) (trauma/hemorrhage, THFx), while another 12 underwent sham procedures. Mice from young (17-26 weeks) and aged (64-72 weeks) groups (n=6) were included. After 24h, lung injury was assessed by hematoxylin-eosin staining, prosurfactant protein C (SPC) levels, HMGB1, and Muc5ac qRT-PCR. Gene expression of Nlrp3 and Il-1β, and protein levels of IL-6 and IL-1β in lung tissue and bronchoalveolar lavage fluid were determined. Levels of lung-infiltrating polymorphonuclear leukocytes (PMNL) and activated caspase-3 expression to assess apoptosis, as well as NLRP3, ASC, and Gasdermin D (GSDMD) to assess the expression of inflammasome components were analyzed via immunostaining. To investigate the role of NF-κB signaling, protein expression of phosphorylated and non-phosphorylated p50 were determined by western blot.ResultsMuc5ac, and SPC as lung protective proteins, significantly declined in THFx versus sham. THFx-aged exhibited significantly lower SPC and higher HMGB1 levels versus THFx-young. THFx significantly increased activated caspase-3 versus both sham groups, and THFx-aged had significantly more caspase-3 positive cells versus THFx-young. IL-6 significantly increased in both sham and THFx-aged groups versus corresponding young groups. THFx significantly enhanced PMNL in both groups versus corresponding sham groups. This increase was further heightened in THFx-aged versus THFx-young. Expression of p50 and phosphorylated p50 increased in all aged groups, and THFx-induced p50 phosphorylation significantly increased in THFx-aged versus THFx-young. THFx increased the expression of inflammasome markers IL-1β, NLRP3, ASC and GSDMD versus sham, and aging further amplified these changes significantly.ConclusionThis study’s findings suggest that the aging process exacerbates the excessive inflammatory response and damage to the lung following trauma. The underlying mechanisms are associated with enhanced activation of NF-κB and increased expression of inflammasome components.
DNAJC8: a prognostic marker and potential therapeutic target for hepatocellular carcinoma
Authors: Zhang Zhibo , Ju Mingxiu , Tang Zhongming , He Zhen , Hua Shengni 
Published: January 2024

BackgroundHepatocellular carcinoma (HCC) is the most common type of liver cancer, accounting for ~90% of the total cases. DnaJ heat shock protein family member C8 (DNAJC8), belonging to the heat shock protein 40 (HSP40) family, is known to regulate cancer biology function. However, the role of DNAJC8 on HCC development remains unknown.MethodsThe Cancer Genome Atlas, GTEx, cBioPortal, and Human Protein Atlas were used to analyze the expression and clinical significance of DNAJC8 in HCC. Two HCC cell lines, MHCC-97H and Huh-7, were utilized to determine the biological function of DNAJC8.ResultsDNAJC8 expression was upregulated in HCC tissues and correlated with poor clinical prognosis. It was closely related to spliceosome, nucleocytoplasmic transport, and cell cycle and might be involved in the formation of tumor immunosuppressive microenvironment. Knockdown of DNAJC8 severely inhibited HCC cell proliferation and induced apoptosis.ConclusionOur study demonstrate that DNAJC8 functions as an oncogene in HCC and hence may be used as a potential therapeutic target and prognostic marker for HCC.
The fractured lens: a controversial revision of the International Classification of Primary Care
Authors: Soler Jean K. , Buono Nicola , Cardillo Elena , Frese Thomas , Vinker Shlomo , Ungan Mehmet 
Published: January 2024

BackgroundThe International Classification of Primary Care (ICPC) has represented the international standard reduction for measuring the content of primary care for over 30 years. In the process of its third revision, its authors, the Wonca International Classification Committee (WICC), delegated a major part of the technical work to a purposely formed Consortium. However, in the process of such revision, standard classification principles and rules have been inconsistently applied with the result that ICPC-3 has been published with major errors and an inconsistent structure.ObjectivesTo formally describe and critically appraise the revision process of ICPC-3.MethodsThe formal review of ICPC-3 performed by an expert group within WICC and commissioned by the Executive Council of Wonca Europe is presented in abridged form.ResultsICPC-3 as currently presented introduces major departures from formal classification principles and rules, besides other major errors and inconsistencies, all of which are listed and described.ConclusionMajor changes in ICPC-3 defy categorisation and conceptualisation standards. ICPC-3 now represents an untested departure from international standard presentations, without a formal academic base. The direct inclusion of measures of functioning in a classification of reasons for encounter and health problems fails to address the dichotomy of these domains, the boundaries of and relationships between which are not satisfactorily resolved by the system. Analysis of ICPC-3 data will require the development and implementation of alternative, as yet undefined, models of the relationships between disease and health. By including different domains without resolving ambiguity, and by splitting function from other body systems, ICPC-3 becomes an internally fractured instrument.
Translation of the working alliance inventory short revised into Italian using a Delphi procedure and a forward-backward translation
Authors: Buono Nicola , Sassier Béatrice , Thulesius Hans , Hoffman Robert , Nabbe Patrice , Petek Davorina , Le Reste Jean Yves 
Published: January 2024

IntroductionEnhancing treatment adherence, especially for chronic diseases, can be achieved through therapeutic alliance, potentially elevating the quality of care. An instrument to evaluate the therapeutic alliance could be beneficial in routine clinical settings, educational environments, and extensive research efforts at national and European levels. In this study, we translated therapist and patient versions of the Working Alliance Inventory Short Revised (WAI-SR) into Italian.MethodologyAn email-based Delphi method was employed for the English-to-Italian translation, incorporating a forward-backward process. The initial translation team comprised two Italian family physicians proficient in English, a linguist, and a psychiatrist. The forward translation was then reviewed by 18 Italian family physicians through a Delphi process and was subjected to a backward translation by two Italian English teachers. A cultural correspondence was subsequently identified to adjust translations within a national and international framework.ResultsAll 18 experts fully engaged in the Delphi process, and consensus was achieved by the second Delphi round. A cultural check checked for discrepancies regarding linguistic consistency with other translations and found no difference.ConclusionThis Italian translation of the WAI-SR is expected to support Italian family physicians aiming to enhance their clinical practice and therapeutic outcomes. It could also be a valuable tool for Italian medical students to foster therapeutic relationships and improve their communication skills.
Clinical application of CT-based radiomics model in differentiation between laryngeal squamous cell carcinoma and squamous cell hyperplasia
Authors: Cui Fengzhi , Khodrog Osama A. , Liu Wei , Liu Jianhua , Yuan Qinghai 
Published: January 2024

ObjectiveTo evaluate the clinical application of the CT-based radiomics prediction model for discriminating SCC and SCH.MethodsA total of 254 clinical samples were selected from 291 patients with larynx-occupying lesions who underwent primary surgery. All lesions were validated via histopathological examination at The Second Hospital of Jilin University between June 2004 and December 2019. All patients were randomly allocated to the training (n = 177) and validation (n = 77) cohorts. After the acquisition of CT images, manual 3D tumor segmentation was performed using the CT images of the arterial, venous, and non-contrast phases via ITK-SNAP software. Subsequently, radiomics features were extracted using A.K. software. Based on the above features, three different diagnostic models (CTN, CTA+CTV, and CTN+CTA+CTV) were constructed to classify squamous cell carcinoma (SCC) and squamous cell hyperplasia (SCH). Additionally, receiver operating characteristic (ROC) and decision curve analysis (DCA) curves were measured to evaluate the diagnostic characteristics and clinical safety of the proposed three prognostic models.ResultsIn the radiomic prediction Model 1 (CTN), the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the training cohorts in differentiating SCC and SCH were 0.883, 0.785, 0.645, 1.000, 1.000, and 0.648, while in the testing cohorts, these values were 0.852, 0.792, 0.66, 1.000, 1.000, and 0.652, respectively. In the radiomic prediction Model 2 (CTA+CTV), the AUC, accuracy, sensitivity, specificity, PPV, and NPV values of the training cohorts were 0.965, 0.91, 0.916, 0.9, 0.933, and 0.875, respectively, while in the testing cohorts, the corresponding values were 0.902, 0.805, 0.851, 0.733, 0.833, and 0.759, respectively. In the radiomic prediction Model 3(CTN+CTA+CTV), the AUC, accuracy, sensitivity, specificity, PPV, and NPV values of the training cohorts were 0.985, 0.944, 0.953, 0.929, 0.953, and 0.929, while in the testing cohorts, the corresponding values were 0.965, 0.857, 0.894, 0.8, 0.875, and 0.828, respectively.ConclusionThe radiomic prediction Model 3, based on the arterial-venous-plain combined scan phase of CT, achieved promising diagnostic performance, expected to be regarded as a preoperative imaging tool in classifying SCC and SCH to guide clinicians to develop individualized treatment programs.
Unveiling Curvularia tuberculata-induced leaf anomalies in Rhododendron ferrugineum: implications in cultural-ecological conservation and harnessing microbial intervention in socio-economic advancement
Authors: Dhar Juhita , Hazra Aishee , Patra Riddhisha , Kumar Varun , Subramaniyan Vetriselvan , Kumarasamy Vinoth , Mitra Arup Kumar , Sayed Amany A. , Aleya Lotfi , El-Demerdash Fatma M. , Almutairi Mikhlid H. , Akash Shopnil , Abdel-Daim Mohamed M. , Kant Achal , Dhara Bikram 
Published: January 2024

IntroductionThe research focuses on Rhododendron ferrugineum L., Nepal’s national flower and Uttarakhand’s state tree, thriving in high-altitude mountain ecosystems.Methodology and ResultA study conducted in Himachal Pradesh (Latitude: N 31° 6’ 2.0088”, Longitude: E 77° 10’ 29.9136”) identified leaf anomalies resembling rust-like manifestations in R. ferrugineum. These anomalies were traced back to the pathogenic fungus Curvularia tuberculata, marking the first documented case of its impact on R. ferrugineum in India.DiscussionThis discovery emphasizes the need for vigilant monitoring, disease management research, and conservation efforts to protect the cultural and ecological significance of this iconic shrub. Beyond its immediate findings, the study introduces a novel dimension to Indian flora by associating C. tuberculata with R. ferrugineum, historically linked to monocotyledonous crops. The research methodology combines traditional microscopic examination with advanced genomic sequencing and phylogenetic analysis, enhancing pathogen identification accuracy.Future prospectIn a broader context, this research aligns with the United Nations Sustainable Development Goals (SDGs) by highlighting the importance of environmental preservation, conservation, and sustainable management. It underscores the intricate interplay between biodiversity, cultural heritage, and the need for holistic solutions. Overall, this study calls for proactive measures to protect R. ferrugineum’s cultural and ecological heritage and emphasizes the significance of interdisciplinary approaches in addressing emerging ecological threats.
A MALDI-TOF mass spectrometry-based method for detection of copy number variations in BRCA1 and BRCA2 genes
Authors: Zhou Hongjun , He Xin , Zhao Jiadong , Mei Zhu , Zhang Xiayan , Yuan Wen , Dong Hui 
Published: January 2024

Background: Identifying germline mutations in BRCA1 and BRCA2 genes (BRCAs) would benefit the carriers in multiple aspects. In addition to single-nucleotide variations and small indels, copy number variations (CNVs) is also an indispensable component of identifiable mutations in BRCAs. A sensitive, rapid and throughput-flexible method to detect CNVs would be preferred to meet the rising clinical requirements for BRCAs testing.Methods: We developed a MALDI-TOF-MS-based method (MS assay) which included three steps: first, multiplex end-point PCR followed by a single base extension reaction; second, automated analyte transfer and data acquisition; third, data analysis. We applied MS assay to detect CNVs in BRCAs in 293 Chinese patients with ovarian or pancreatic cancer. All the samples were examined by targeted next-generation sequencing (TS) simultaneously. Samples were further cross-validated by multiplex ligation-dependent probe amplification (MLPA) if the results from MS assay and TS were inconsistent. Long range PCR was then applied to identify the exact breakpoints in BRCAs.Results: MS assay introduced highly multiplexed panels to detect CNVs of BRCAs semi-quantitatively. Simplified on-board data analysis was available for MS assay and no complex bioinformatics was needed. The turnaround time of MS assay was less than 8 hours with a hands-on time of only 40 min. Compared to TS, MS assay exhibited higher sensitivity (100% vs. 75%) and was more flexible in throughput, with the reagent cost per sample remaining constant no matter how many samples were examined per assay. A total of eight CNVs in BRCAs were detected from the 293 samples, and the molecular breakpoints were successfully identified in five samples through long-range PCR followed by Sanger sequencing.Conclusion: Our results suggested that MS assay might be an effective method in primary screening for CNVs in genes such as BRCAs, especially when short turnaround time and/or high sensitivity is a top priority.
Generation of human TMEM16F-specific affibodies using purified TMEM16F
Authors: Kim Eunyoung , Bang Jinho , Sung Ji Hye , Lee Jonghwan , Shin Dae Hwan , Kim Sunghyun , Lee Byoung-Cheol 
Published: January 2024

Introduction: TMEM16 family proteins are involved in a variety of functions, including ion transport, phospholipid scrambling, and the regulation of membrane proteins. Among them, TMEM16F has dual functions as a phospholipid scramblase and a nonselective ion channel. TMEM16F is widely expressed and functions in platelet activation during blood clotting, bone formation, and T cell activation. Despite the functional importance of TMEM16F, the modulators of TMEM16F function have not been sufficiently studied.Method: In this study, we generated TMEM16F-specific affibodies by performing phage display with brain-specific TMEM16F (hTMEM16F) variant 1 purified from GnTi− cells expressing this variant in the presence of digitonin as a detergent. Purified human TMEM16F protein, which was proficient in transporting phospholipids in a Ca2+-dependent manner in proteoliposomes, was coated onto plates and then the phage library was added to fish out TMEM16F-binding affibodies. For the validation of interaction between affibodies and TMEM16F proteins, ELISA, bio-layer interferometry, and size exclusion chromatography were conducted.Results and Discussion: As a result, the full sequences of 38 candidates were acquired from 98 binding candidates. Then, we selected 10 candidates and purified seven of them from E. coli expressing these candidates. Using various assays, we confirmed that two affibodies bound to human TMEM16F with high affinity. These affibodies can be useful for therapeutical and diagnostic applications of TMEM16F-related cancer and neurodegenerative diseases. Future studies will be required to investigate the effects of these affibodies on TMEM16F function.
Effects of remote combine exercise-music training on physical and cognitive performance in patients with Alzheimer’s disease: a randomized controlled trial
Authors: Shokri Ghazaleh , Mohammadian Fatemeh , Noroozian Maryam , Amani-Shalamzari Sadegh , Suzuki Katsuhiko 
Published: January 2024

IntroductionThis study aimed to investigate the effects of combined remote music and exercise training on the cognitive, psychological, and physical function of patients with Alzheimer’s disease (AD).MethodsForty-one AD patients were randomly allocated to three groups, including control (C), training (T), and training with music (TM) groups. Participants were evaluated by cognitive and performance test batteries before and after the interventions. Both experimental groups performed 36 remote workouts in 3 months online via WhatsApp video call individually with the trainer. Training included simple and varied movements of all physical indicators. The number of sets began with two sets and progressively increased to one set every month, 5–10 repetitions per set. The overload was applied by reducing the break between sets every week. The TM group performed the same exercises while listening to Mozart and traditional Iranian songs.ResultsWe observed a significant main, group, time, and interaction effect on Romberg (ηp2:0.72), 30 s chair sit and stand (ηp2:0.75), and walking on steppe test (ηp2:0.63). Furthermore, there was a significant main time and interaction effect on push-ups (ηp2:0.43), sit and reach (ηp2:0.64), and MMSE (ηp2:0.76). In all variables, two experimental groups demonstrated substantial improvements than the C group (p &lt; 0.01). In addition, the TM group (27.8%) showed a significant improvement compared to the C group (−6.4%) and the T group (12.2%) in MMSE.ConclusionCombined remote training with listening to music as adjuvant treatment is an appropriate item to improve the cognitive and physical performance of Alzheimer’s patients, especially during the COVID-19 pandemic.