bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Isolated Coronary Microvascular Disease Diagnosed Using Various Measurement Modalities on Prognosis: An Updated Systematic Review and Meta-Analysis
Authors: Luo Xingyu , Liu Yaokun , Liu Jiahui , Zhang Jin , Gao Songyuan , Zhang Yanyan , Zhou Zuoyi , Xie Haotai , Hou Weijie , Gong Yan Jun , Zheng Bo , Zhang Yan , Li Jianping
Published: October 2023

Introduction: The main aim of this study was to investigate the impact of isolated coronary microvascular disease (CMD) as diagnosed via various modalities on prognosis. Methods: A systematic literature review of PubMed, Embase, and Cochrane Library databases was conducted to identify relevant studies published up to March 2023. Included studies were required to measure coronary microvascular function and report outcomes in patients without obstructive coronary artery disease (CAD) or any other cardiac pathological characteristics. The primary endpoint was all-cause mortality, and the secondary endpoint was a major adverse cardiac event (MACE). Pooled effects were calculated using random effects models. Results: A total of 27 studies comprising 18,204 subjects were included in the meta-analysis. Indices of coronary microvascular function measurement included coronary angiography-derived index of microcirculatory resistance (caIMR), hyperemic microcirculatory resistance (HMR), coronary flow reserve (CFR), and so on. Patients with isolated CMD exhibited a significantly higher risk of mortality (OR: 2.97, 95% CI, 1.91–4.60, p < 0.0001; HR: 3.38, 95% CI, 1.77–6.47, p = 0.0002) and MACE (OR: 5.82, 95% CI, 3.65–9.29, p < 0.00001; HR: 4.01, 95% CI, 2.59–6.20, p < 0.00001) compared to those without CMD. Subgroup analysis by measurement modality demonstrated consistent and robust pooled effect estimates in various subgroups. Conclusion: CMD is significantly associated with an elevated risk of mortality and MACE in patients without obstructive CAD or any other identifiable cardiac pathologies. The utilization of various measurement techniques may have potential advantages in the management of isolated CMD.
Prognostic Markers in the Era of Targeted Therapies
Authors: Kang Sorang , Ahn Inhye E.
Published: October 2023

Background: Small molecules targeting Bruton’s tyrosine kinase (BTK) and B-cell lymphoma-2 have become the standard of care for the treatment of chronic lymphocytic leukemia (CLL), replacing chemoimmunotherapy (CIT) in most clinical settings. Ongoing trials explore targeted combinations and minimal residual disease-driven treatment cessation. These dramatic shifts in the current and upcoming treatment landscape of CLL raise the need to reevaluate existing prognostic markers and develop novel ones. Summary: This review examines prognostic markers in CLL patients treated with standard and investigational targeted therapies. Specifically, initial treatment of TP53 aberrant patients with a BTK inhibitor can achieve 70% progression-free survival (PFS) at 5 years, outperforming the 15% 5-year PFS with a CIT regimen containing fludarabine, cyclophosphamide, and rituximab (FCR). The prognostic implications of the immunoglobulin heavy chain variable gene (IGHV) mutation status have also changed. Unmutated IGHV is associated with inferior PFS and overall survival after FCR and inferior PFS with fixed-duration therapy with venetoclax and anti-CD20 monoclonal antibody but not with continuous BTK inhibitor treatment. Key Messages: (1) Genetic variables (e.g., TP53 aberration, IGHV mutation, complex karyotype) have a prognostic significance in CLL patients treated with targeted therapy. (2) Understanding the prognostic and predictive values of these markers is critical for the development of a risk-adapted treatment strategy in CLL.
Mesenchymal Stromal Cells Facilitate Neutrophil-Trained Immunity by Reprogramming Hematopoietic Stem Cells
Authors: Ng Julie , Marneth Anna E. , Griffith Alec , Younger Daniel , Ghanta Sailaja , Jiao Alan , Willis Gareth , Han Junwen , Imani Jewel , Niu Bailin , Keegan Joshua W. , Hancock Brandon , Guo Fei , Shi Yang , Perrella Mark A. , Lederer James A.
Published: October 2023

Novel therapeutics are urgently needed to prevent opportunistic infections in immunocompromised individuals undergoing cancer treatments or other immune-suppressive therapies. Trained immunity is a promising strategy to reduce this burden of disease. We previously demonstrated that mesenchymal stromal cells (MSCs) preconditioned with a class A CpG oligodeoxynucleotide (CpG-ODN), a Toll-like receptor 9 (TLR9) agonist, can augment emergency granulopoiesis in a murine model of neutropenic sepsis. Here, we used a chimeric mouse model to demonstrate that MSCs secrete paracrine factors that act on lineage-negative c-kit+ hematopoietic stem cells (HSCs), leaving them “poised” to enhance emergency granulopoiesis months after transplantation. Chimeric mice developed from HSCs exposed to conditioned media from MSCs and CpG-ODN-preconditioned MSCs showed significantly higher bacterial clearance and increased neutrophil granulopoiesis following lung infection than control mice. By Cleavage Under Targets and Release Using Nuclease (CUT&RUN) chromatin sequencing, we identified that MSC-conditioned media leaves H3K4me3 histone marks in HSCs at genes involved in myelopoiesis and in signaling persistence by the mTOR pathway. Both soluble factors and extracellular vesicles from MSCs mediated these effects on HSCs and proteomic analysis by mass spectrometry revealed soluble calreticulin as a potential mediator. In summary, this study demonstrates that trained immunity can be mediated by paracrine factors from MSCs to induce neutrophil-trained immunity by reprogramming HSCs for long-lasting functional changes in neutrophil-mediated antimicrobial immunity.
Successful Rechallenge with Osimertinib following Osimertinib-Induced Ventricular Tachycardia: A Case Report
Authors: Saito Zentaro , Imakita Takuma , Ito Takanori , Oi Issei , Kanai Osamu , Fujita Kohei , Tachibana Hiromasa , Mio Tadashi
Published: October 2023

Osimertinib, a third-generation tyrosine kinase inhibitor, is the first-line treatment for metastatic non-small cell lung cancer (NSCLC) with sensitizing epidermal growth factor receptor (EGFR) mutations. It is known to cause drug-induced cardiotoxicity, including QT prolongation syndrome, heart failure, and ventricular arrhythmias, which can lead to sudden death. Once severe arrhythmias occur, it is difficult to continue osimertinib treatment. We report a case of a 66-year-old woman with recurrent NSCLC after concurrent chemoradiotherapy who experienced osimertinib-induced ventricular arrhythmia-causing syncope. The patient was initially treated with concurrent chemoradiotherapy, and genetic testing revealed EGFR exon 19 deletion. Three years following treatment initiation, the primary tumor progressed, and new bone metastases developed. The patient was diagnosed with recurrent NSCLC and was treated with targeted therapy with osimertinib. On the 10th day of osimertinib administration, syncope occurred. Electrocardiography showed polymorphic non-sustained ventricular tachycardia, which was believed to be the cause of syncope. The patient was switched to erlotinib. Two and a half years later, disease progression in the primary lesion was observed. A liquid biopsy revealed an EGFR T790M resistance mutation. Therefore, osimertinib (40 mg) was administered every alternate day. After confirming the absence of palpitations and arrhythmias on electrocardiogram, the osimertinib dosing was increased to 40 mg daily. Thereafter, no further events occurred, and tumor shrinkage was observed. Low-dose osimertinib rechallenge after induced ventricular arrhythmia may be considered an option under close monitoring; however, osimertinib rechallenge must be carefully selected based on the risk-benefit analysis.
Discrepancies in Hormone Receptor and HER2 Expression between Malignant Serous Effusions and Paired Tissues from Primary or Recurrent Breast Cancers
Authors: Nikas Ilias P. , Lim Sojung , Im Seock-Ah , Lee Kyung-Hun , Lee Dae-Won , Lee Hyebin , Ryu Han Suk
Published: October 2023

Introduction: Immunohistochemistry (IHC) for the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) biomarkers has prognostic and therapeutic value in breast cancer. This study aimed to compare the expression of ER, PR, and HER2 between paired malignant effusions and tissue samples of breast cancer. Methods: Our electronic archive was searched for all effusions diagnosed as breast carcinomas within a pre-defined period (January 2018–October 2021). Next, their cell blocks (CBs) were subjected to ER, PR, HER2 IHC, or in situ hybridization, in addition to EGFR IHC. The expression of hormone receptors (HRs) and HER2 was subsequently compared between tissue and effusion cytology samples derived from the same patients. Results: Only 2/76 (2.6%) of the breast cancer patients analyzed showed a malignant effusion at their initial presentation. ER, PR, and HER2 discordance rates between paired malignant effusions and tissue samples obtained at initial diagnosis were 24.3% (17/73), 40.8% (29/71), and 9.1% (6/66), respectively. The HR–/HER2– status was found more often at effusions compared to paired tissue biopsies obtained at initial diagnosis (30/70 vs. 17/70; p < 0.001). In addition, the HR–/HER2– status was significantly associated with an earlier development of a malignant effusion, when found at initial diagnosis (p < 0.001; log-rank test), first recurrence/metastasis (either solid or effusion) (p = 0.012; log-rank test), effusion samples (p = 0.007; log-rank test), and any tumor sample obtained (p = 0.009; log-rank test). Lastly, EGFR overexpression in the HR–/HER2– effusion samples was significantly associated with a shorter post-effusion survival (p = 0.019; log-rank test). Conclusion: Serous effusion cytology provides high-quality material for ancillary techniques, especially when CBs are prepared, reflecting cancer heterogeneity.
Clinicopathological Features and Outcomes of IgA Nephropathy with Serum Antineutrophil Cytoplasmic Autoantibody Positivity
Authors: Li Wenchao , Chen Ruifan , Chen Wei , Huang Fengxian , Xia Xi
Published: October 2023

Introduction: IgA nephropathy (IgAN) with serum antineutrophil cytoplasmic autoantibody (ANCA) positivity is uncommon. This study analyzed the clinicopathologic features and prognosis of IgAN patients with serum ANCA positivity. Methods: 2,864 IgAN patients were tested for ANCA by the indirect immunofluorescence assay and chemiluminescence immunoassay. Patients with serum ANCA positivity (n = 85) were identified, and their clinical, pathological, and prognostic characteristics were analyzed. They were compared with ANCA-negative IgAN patients (n = 170) and ANCA-associated systemic vasculitis (AAV) with renal involvement patients (n = 85) selected randomly. Results: 2.97% (85/2,864) of IgAN were ANCA positive, and 4 patients were diagnosed as having crescentic IgAN with ANCA positivity. The clinicopathological characteristics of ANCA-positive IgAN patients were comparable to ANCA-negative IgAN patients, but they had higher antinuclear antibody (ANA)-positive rates, lower levels of renal interstitial inflammation, and fewer immune depositions than ANCA-negative IgAN patients. Compared with AAV patients, ANCA-positive IgAN patients were younger and had fewer extrarenal manifestations, milder renal damage, and more immune complex depositions. The renal outcomes were similar between IgAN patients with and without ANCA positivity. Multivariate Cox analysis revealed that in IgAN patients with ANCA positivity, male, ANA positivity, higher serum creatinine and proteinuria, and more severe renal tubular atrophy/interstitial fibrosis were risk factors for adverse renal outcomes. Conclusion: The clinical, pathological features and prognosis of ANCA-positive IgAN patients were similar to those of ANCA-negative IgAN patients except for higher ANA-positive rate, milder renal inflammation, and fewer immune depositions. ANA positivity was an independent risk factor for adverse renal outcomes in ANCA-positive IgAN patients.
At the Head and Heart of Oxytocin’s Stress-Regulatory Neural and Cardiac Effects: A Chronic Administration RCT in Children with Autism
Authors: Alaerts Kaat , Daniels Nicky , Moerkerke Matthijs , Evenepoel Margaux , Tang Tiffany , Van der Donck Stephanie , Chubar Viktoria , Claes Stephan , Steyaert Jean , Boets Bart , Prinsen Jellina
Published: October 2023

Introduction: Intranasal administration of oxytocin presents a promising new approach to reduce disability associated with an autism spectrum disorder diagnosis. Previous investigations have emphasized the amygdala as the neural foundation for oxytocin’s acute effects. However, to fully understand oxytocin’s therapeutic potential, it is crucial to gain insight into the neuroplastic changes in amygdala circuitry induced from chronic oxytocin administrations, particularly in pediatric populations. Objective: We aimed to examine the impact of a 4-week course of intranasal oxytocin on amygdala functional connectivity in children with autism, compared to placebo. Additionally, we investigated whether oxytocin improves cardiac autonomic arousal, as indexed by high-frequency heart rate variability. Methods: Fifty-seven children with autism aged 8–12 years (45 boys, 12 girls) participated in a double-blind, randomized pharmaco-neuroimaging trial involving twice-daily administrations of intranasal oxytocin or placebo. Resting-state fMRI scans and simultaneous, in-scanner heart rate recordings were obtained before, immediately after, and 4 weeks after the nasal spray administration period. Results: Significant reductions in intrinsic amygdala-orbitofrontal connectivity were observed, particularly at the 4-week follow-up session. These reductions were correlated with improved social symptoms and lower cardiac autonomic arousal. Further, oxytocin’s neural and cardiac autonomic effects were modulated by epigenetic modifications of the oxytocin receptor gene. The effects were more pronounced in children with reduced epigenetic methylation, signifying heightened expression of the oxytocin receptor. Conclusion: These findings underscore that a 4-week oxytocin administration course decreases amygdala connectivity and improves cardiac autonomic balance. Epigenetic modulators may explain inter-individual variation in responses to oxytocin.
Effects of Lobectomy versus Sub-Lobar Resection on the Survival in Adults with Stage IA Left Upper Lobe Non-Small Cell Lung Cancer: A Retrospective Cohort Study Based on the Surveillance, Epidemiology, and End Results Database
Authors: Wen Huanshun , Liang Chaoyang
Published: October 2023

Introduction: The objective of this study was to compare the survival after lobectomy (LR) and sub-lobar resection (SLR) of the left upper lobe (LUL) among non-small cell lung cancer (NSCLC) patients with stage IA. Methods: This retrospective cohort research analyzed public data collected by the Surveillance, Epidemiology, and End Results (SEER) database. Tumor characteristics were determined based on the International Classification of Diseases for Oncology, 3rd edition (ICD-O-3). Propensity score matching (PSM) analysis was performed with a ratio of 1:1. Univariate and multivariable Cox proportional regression analyses were used to assess the effects of LR and SLR on the survival of the patients, with hazard ratios (HRs) and 95% confidence intervals (95% CIs). The effects were further evaluated by different subgroups of age, gender, tumor grades, histologic types, T stages. Results: Of the total 2,649 patients, 1,907 underwent the LR and 742 received SLR. Totally, 998 patients died at the end of the follow-up. The median survival time of all patients was 66 (49, 87) months. After adjusting the age, gender, race, tumor grade, histologic type, T stage, examined lymph nodes, radiation, and chemotherapy, NSCLC patients with stage IA who received SLR had higher odds of death in comparison with these patients who received LR (HR = 1.424, 95% CI: 1.227–1.652). After PSM, SLR was associated with higher odds of death in the patients (HR = 1.35, 95% CI: 1.10–1.66). Similar results were discovered in different subpopulations. Conclusion: The SLR was inferior to LR on the survival of NSCLC patients with stage IA.
Extraction of Interoperable Data from Healthcare Documents by Identifying Common Data Elements: An Analysis of Radiation Therapy Planning CT Physician Order Entry Records
Authors: Dennstädt Fabio , Putora Paul Martin , Heuser Michael , Vlaskou Badra Eugenia , Baumert Brigitta Gertrud , Leiser Dominic , Cihoric Nikola
Published: October 2023

Introduction: Documentation as well as IT-based management of medical data is of ever-increasing relevance in modern medicine. As radiation oncology is a rather technical, data-driven discipline, standardization, and data exchange are in principle possible. We examined electronic healthcare documents to extract structured information. Planning CT order entry documents were chosen for the analysis, as this covers a common and structured step in radiation oncology, for which standardized documentation may be achieved. The aim was to examine the extent to which relevant information may be exchanged among different institutions. Materials and Methods: We contacted representatives of nine radiation oncology departments. Departments using standardized electronic documentation for planning CT were asked to provide templates of their records, which were analyzed in terms of form and content. Structured information was extracted by identifying definite common data elements, containing explicit information. Relevant common data elements were identified and classified. A quantitative analysis was performed to evaluate the possibility of data exchange. Results: We received data of seven documents that were heterogeneous regarding form and content. 181 definite common data elements considered relevant for the planning CT were identified and assorted into five semantic groups. 139 data elements (76.8%) were present in only one document. The other 42 data elements were present in two to six documents, while none was shared among all seven documents. Conclusion: Structured and interoperable documentation of medical information can be achieved using common data elements. Our analysis showed that a lot of information recorded with healthcare documents can be presented with this approach. Yet, in the analyzed cohort of planning CT order entries, only a few common data elements were shared among the majority of documents. A common vocabulary and consensus upon relevant information is required to promote interoperability and standardization.
Gender, Socioeconomic, and Health Characteristics Associated to Dermatological Visits in Italy: Secondary Analysis of a National Cross-Sectional Survey
Authors: Dolcini Jacopo , Ponzio Elisa , Campanati Anna , D’Errico Marcello Mario , Barbadoro Pamela
Published: October 2023

Background: Very few studies have investigated possible role of sociodemographic factors in terms of differences in access to dermatologic visits, and almost all of them have been conducted in health system realities where insurance companies play an important role in terms of access to healthcare providers. To our knowledge in Italy, there is lack of studies carried out with the aim to investigate possible role of sociodemographic factors regarding differences in outpatient dermatologic use for a variety of dermatologic conditions. Indeed, some investigations have been focused on specific dermatologic conditions without analyzing the big and extremely wide picture of skin diseases. Objective: The aim of this study was to analyze possible variables associated with tendency to access dermatological visits. Methods: We analyzed data from the multipurpose Italian cross-sectional Health Interview Survey routinely carried out by the Italian National Institute of Statistics (ISTAT). Mixed effect logistic regression models have been built to evaluate factors independently associated with dermatological visit. Results: Of the 119,073 subjects, only 2.3% underwent a dermatological visit. People older than 44 years old are less likely of undergoing a dermatological visit as well as people married/cohabiting, separated/divorced, and widowed, with low economic resources and living in southern and islands areas. Upper education levels are associated to increased probability of having a dermatological visit as well as lowering class of self-perceived health status and living in northern and central areas. Conclusion: This study shows an association between the odds of having dermatological visits and some sociodemographic factors. This could generate possible health disparities in dermatological disease outcomes.
The Cancer Cachexia Index Can Be Used to Prognostically Predict Patients with Gastric Cancer Undergoing Gastrectomy
Authors: Sakurai Katsunobu , Kubo Naoshi , Hasegawa Tsuyoshi , Nishimura Junya , Iseki Yasuhito , Nishii Takafumi , Inoue Toru , Yashiro Masakazu , Nishiguchi Yukio , Maeda Kiyoshi
Published: October 2023

Introduction: Cancer cachexia occurs in cancer patients more frequently as the cancer progresses, with a negative impact on treatment outcomes. In this study, we sought to clarify the clinical impact of a cancer cachexia index (CXI) in patients with gastric cancer (GC) undergoing gastrectomy. Methods: Between January 2013 and December 2018, we reviewed data from 556 patients treated for GC at our hospital. CXI was calculated using skeletal muscle index (SMI), serum albumin, and neutrophil-lymphocyte ratios (NLR). Patients were divided into high (n = 414) or low CXI (n = 142) groups. We investigated the clinical impact of CXI in patients with GC undergoing gastrectomy. Results: Multivariate analyses of 5-year overall survival (OS) and cancer-specific survival (CSS) rates indicated that a low CXI was independently associated with unfavorable outcomes for patients with GC. In multivariate analyses, SMI was independent predictor of OS but not CSS. NLR was not an independent predictor of either OS or CSS. Complication incidences (≥ Clavien Dindo 3) were non-significantly higher in the low (vs. high) CXI group. Conclusion: CXI was a more valuable prognostic biomarker when compared with SMI or NLR in GC patients undergoing gastrectomy. We suggest that patients with low CXI values should be given more comprehensive treatment, including exercise and nutritional therapy to improve clinical outcomes.
Effect of Diabetes Mellitus Type 2 on Voice: A Systematic Review and Meta-Analysis
Authors: Hamdan Abdul-Latif , Abi Zeid Daou Christophe , Hosri Jad , Abou Raji Feghali Patrick , Jabbour Christopher , Alam Elie , Mourad Marc
Published: October 2023

Introduction: Diabetes mellitus type 2 is a growing health concern that affects several systems in the body, among which is the phonatory apparatus. Voice may be affected in view of the high prevalence of myopathy and neuropathy in diseased subjects. The authors aimed to answer the following question: does type 2 diabetes have an effect on voice? Methods: The systematic review included search terms such as “speech, voice, larynx, glucose, diabetes, and hyperglycemia.” The search strategy yielded 221 articles, only five of which satisfied the inclusion criteria. Articles were considered for inclusion using the PRISMA method. Analysis included 321 patients with type 2 diabetes mellitus and 171 controls. All studies included were case-control studies except for one study which was an observational cohort. Six parameters were chosen as endpoints for the systematic review and meta-analysis: the presence/absence of voice complaints, fundamental frequency, jitter, shimmer, noise-to-harmonic ratio, and maximum phonation time. Results: There was no significant difference in the prevalence of voice complaints (i.e., hoarseness) between diabetic patients and control groups. There was also no significant difference in any of the acoustic and aerodynamic measures between patients with type 2 diabetes and controls. These findings can be ascribed to the high resilience of the laryngeal muscles to the adverse effect of systemic diseases. Conclusion: There is no consensus in the literature that the prevalence of voice symptoms in diabetic patients is significantly higher than that reported in healthy subjects.
Effects of Speaking Rate on Variability of Second Formant Frequency Transitions in Dysarthria
Authors: van Brenk Frits , Lowit Anja , Tjaden Kris
Published: October 2023

Introduction: This study examined the utility of multiple second formant (F2) slope metrics to capture differences in speech production for individuals with dysarthria and healthy controls as a function of speaking rate. In addition, the utility of F2 slope metrics for predicting severity of intelligibility impairment in dysarthria was examined. Methods: Twenty three speakers with Parkinson’s disease and mild to moderate hypokinetic dysarthria (HD), 9 speakers with various neurological diseases and mild to severe ataxic or ataxic-spastic dysarthria (AD), and 26 age-matched healthy control speakers (CON) participated in a sentence repetition task. Sentences were produced at habitual, fast, and slow speaking rate. A variety of metrics were derived from the rising F2 transition portion of the diphthong /ai/. To obtain measures of intelligibility for the two clinical speaker groups, 15 undergraduate SLP students participated in a transcription experiment. Results: Significantly shallower slopes were found for the speakers with HD compared to control speakers. Steeper F2 slopes were associated with increased speaking rate for all groups. Higher variability in F2 slope metrics was found for the speakers with AD compared to the two other speaker groups. For both clinical speaker groups, there was a negative association between intelligibility and F2 slope variability metrics, indicating lower variability in speech production was associated with higher intelligibility. Discussion: F2 slope metrics were sensitive to dysarthria presence, dysarthria type, and speaking rate. The current study provided evidence that the use of F2 slope variability measures has additional value to F2 slope averaged measures for predicting severity of intelligibility impairment in dysarthria.
Long-Term Acetylcholinesterase Depletion Alters the Levels of Key Synaptic Proteins while Maintaining Neuronal Markers in the Aging Zebrafish (Danio rerio) Brain
Authors: Karoglu-Eravsar Elif Tugce , Tuz-Sasik Melek Umay , Karaduman Aysenur , Keskus Ayse Gokce , Arslan-Ergul Ayca , Konu Ozlen , Kafaligonul Hulusi , Adams Michelle M.
Published: October 2023

Introduction: Interventions targeting cholinergic neurotransmission like acetylcholinesterase (AChE) inhibition distinguish potential mechanisms to delay age-related impairments and attenuate deficits related to neurodegenerative diseases. However, the chronic effects of these interventions are not well described. Methods: In the current study, global levels of cholinergic, cellular, synaptic, and inflammation-mediating proteins were assessed within the context of aging and chronic reduction of AChE activity. Long-term depletion of AChE activity was induced by using a mutant zebrafish line, and they were compared with the wildtype group at young and old ages. Results: Results demonstrated that AChE activity was lower in both young and old mutants, and this decrease coincided with a reduction in ACh content. Additionally, an overall age-related reduction in AChE activity and the AChE/ACh ratio was observed, and this decline was more prominent in wildtype groups. The levels of an immature neuronal marker were upregulated in mutants, while a glial marker showed an overall reduction. Mutants had preserved levels of inhibitory and presynaptic elements with aging, whereas glutamate receptor subunit levels declined. Conclusion: Long-term AChE activity depletion induces synaptic and cellular alterations. These data provide further insights into molecular targets and adaptive responses following the long-term reduction of AChE activity that was also targeted pharmacologically to treat neurodegenerative diseases in human subjects.
Sensitivity to Thyroid Hormones and Reduced Glomerular Filtration in Children and Adolescents with Overweight or Obesity
Authors: Di Bonito Procolo , Corica Domenico , Marzuillo Pierluigi , Di Sessa Anna , Licenziati Maria Rosaria , Faienza Maria Felicia , Calcaterra Valeria , Franco Francesca , Maltoni Giulio , Valerio Giuliana , Wasniewska Malgorzata
Published: October 2023

Background: Reduced central sensitivity to thyroid hormones (THs) has been observed in euthyroid adults with reduced renal function. This topic is unexplored in young people with overweight or obesity (OW/OB). Objective: The aim of this study was to evaluate the association between sensitivity to TH and mild reduced estimated glomerular filtration rate (MReGFR) in euthyroid children and adolescents with OW/OB. Methods: Data of 788 euthyroid children and adolescents with OW/OB (aged 6–16 years), recruited from seven Italian centers for the care of OW/OB, were evaluated. Peripheral sensitivity to TH was estimated through the FT3/FT4 ratio, while central sensitivity was assessed by estimating TSH index (TSHI), thyrotroph T4 resistance index, thyroid feedback quantile-based index (TFQI), parametric thyroid feedback quantile-based index (PTFQI). MReGFR was defined by an eGFR value ≥60 and <90 mL/min/1.73 m2. Results: Subjects with MReGFR had significantly lower levels of FT3/FT4 ratio (0.43 ± 0.09 vs. 0.44 ± 0.10; p = 0.028) and higher levels of TSH (2.89 ± 1.00 vs. 2.68 ± 0.99; p = 0.019), TSHI (2.95 ± 0.45 vs. 2.85 ± 0.55; p = 0.031), TFQI [1.00 (0.98–1.00) versus 1.00 (0.97–1.00); p = 0.046], and PTFQI (0.66 ± 0.17 vs. 0.60 ± 0.23; p = 0.006) compared with individuals with normal eGFR. Odds ratio of MReGFR raised of 1.2–3.2-fold for each increase of 1 mIU/L in TSH, 1 unit in TSHI, and PTFQI, but not for FT3/FT4 ratio. Conclusion: MReGFR is associated with reduced indices of central sensitivity to TH in euthyroid children and adolescents with OW/OB. This preliminary observation should be confirmed in prospective studies.
ОСВІТНЬО-НАУКОВА ПРОГРАМА ЗА СПЕЦІАЛЬНІСТЮ 091 «БІОЛОГІЯ ТА БІОХІМІЯ»
Authors: Бабінцева Л.Ю. , Горовенко Н. Г. , Дзюблик І. В. , Кирик Д. Л. , Соловйов С. О. , Подольска С. В. , В’юницька Л. В.
Published: October 2023

Біологія XXI століття являється міждисциплінарною та трансдисциплінарною галуззю знань, що не тільки стрімко розвивається, але й потребує висококваліфікованих, конкурентоспроможних, ініціативних, інтегрованих в європейський і світовий науково-освітній простір спеціалістів. Тому біологія як наука про життя знаходить своє відображення в розвитку багатьох наук і технологій сучасного світу -від персональної медицини до біологічних основ психології людини, від розроблення нових біонічних матеріалів і пристроїв до клітинної інженерії та штучного запліднення. Життя розглядається на різних рівнях його організації - від молекули до біосфери. Для поглибленого розуміння біохімічних принципів функціонування клітин in vivo та in vitro як основи сучасної біології у поточному році розширено межі спеціальності та додано складову - біологічна хімія, дослідження з якої охоплюють кілька напрямів, зокрема, статичну, динамічну та функціональну біохімію. Зауважимо, що нові відкриття в галузі біохімії істотно підсилюють рівень світової сучасної медицини, а узагальнення біохімії допомагають висвітлити еволюцію органічного світу та питання про виникнення життя на Землі.
Представлено сучасне бачення навчання майбутніх спеціалістів ступеня доктора філософії за спеціальністю 091 «Біологія та біохімія» галузі знань 09 «Біологія». Серед особливостей сучасної біології виділяємо: вивчення взаємозв'язку біологічного та соціального розвитку людини; щільний зв'язок із низкою високотехнологічних напрямів, що включають молекулярну біологію, молекулярну генетику, системну біомедицину. Практично всі нові напрями та особливості пов'язані із застосуванням інформаційно-комунікаційних і цифрових технологій.
По завершенню навчання, здобувачі вищої освіти третього рівня мають оволодіти загальнонаукови-ми компетентностями, здобути універсальні навики дослідника та мовні компетентності. Тематика курсів професійної підготовки розроблена з метою сприяння здатності інтегрувати знання та розв'язувати складні завдання в мультидисциплінарних і трансдисциплінарних контекстах.
A Large-Scale Field Experiment to Reduce Non-Payments for Water: From Diagnosis to Treatment
Authors: Rockenbach Bettina , Tonke Sebastian , Weiss Arne R.
Published: October 2023

In a field experiment among 9,823 customers of the Namibian water utility, we implement interventions to reduce non-payments. The interventions are based on diagnostic surveys to identify key obstacles to payments. They address informational frictions and apply psychological commitment techniques to narrow the gap between customers' willingness to pay and actual payments. Initially, payments increase by 29% to 55%, making the interventions highly cost-effective. While removing informational frictions has a lasting impact, the commitment techniques produce only short-term effects. We demonstrate the effectiveness and limitations of behavioral interventions in settings where heavy-handed tools, e.g., disconnecting non-payers, are difficult to implement.
Two new species of Stylochaeton (Araceae: Aroideae) from South Africa
Authors: STRUWIG MADELEEN , ROUX PRECIOUS T. LE , SIEBERT STEFAN J. , WYK ABRAHAM E. VAN
Published: October 2023

We are describing here Stylochaeton glaucophyllum and S. sekhukhuniense, two new species from northeastern South Africa. Both species have a restricted distribution and are endemic to the Sekhukhuneland Centre of Plant Endemism, Limpopo and Mpumalanga Provinces, South Africa. The new species occur sympatrically with S. natalense, but never with one another. Stylochaeton glaucophyllum prefers norite and pyroxenite hills and mountains, whereas S. sekhukhuniense is associated with similar rock types in low-lying rocky areas. Both new species have the base of the spadix and infructescence partly below-ground and are mainly associated with open savannah. Stylochaeton glaucophyllum can be distinguished from S. sekhukhuniense in having greenish blue leaves with linear lobes while S. sekhukhuniense has green leaves with elliptic lobes. The leaves of S. glaucophyllum are longer (112–332 mm) than those of S. sekhukhuniense (44–180 mm). The petiolar sheath of S. sekhukhuniense extends into two slender, curling ligulae which are absent in S. glaucophyllum. Also included here is a key to the seven currently accepted species of Stylochaeton in southern Africa (South Africa, Eswatini, Zimbabwe and Mozambique).
Rediscovery of Prosthechea sessiliflora (Orchidaceae, Laeliinae) in the Brazilian Cerrado domain provides valuable taxonomic data and allows nomenclatural adjustments
Authors: VIEIRA TIAGO L. , MORAIS ISA LUCIA DE , BERG CÁSSIO VAN DEN
Published: October 2023

Prosthechea sessiliflora is a Brazilian endemic orchid species notably poorly represented in biological collections. The type material whereabouts is unknown, and the species had no further herbarium specimens until very recently. After the recent rediscovery of the species in the Cerrado domain, a deeper morphological evaluation was possible, as well as necessary nomenclatural adjustments. Herein, we present an updated morphological description of the species, together with a composite digital plate highlighting its morphology, perform a lectotypification and epitypification, and provide a preliminary conservation assessment of the species, in addition to nomenclatural and taxonomic notes.
Nagisavelia hikarui, a new genus and species of Mesoveliinae (Hemiptera: Heteroptera: Mesoveliidae) inhabiting shingle beaches in Japan
Authors: WATANABE KOHEI , NAKAJIMA JUN , HAYASHI MASAKAZU
Published: October 2023

A new genus and species of Mesoveliinae, Nagisavelia hikarui n.gen. and n.sp., is described from rocky intertidal beaches in Japan. The new taxon is compared to the other 10 genera of Mesoveliinae, and a character matrix for the identification of eight genera is provided. A key to facilitate the identification of the seven species of Mesoveliidae now reported from Japan is also provided.
Circ-Slain2 Alleviates Cartilage Degradation and Inflammation of TMJOA
Authors: Pan X. , Zhao Z. , Huang X. , Cen X.
Published: October 2023

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease with the cessation of matrix anabolism and aggravation of inflammation, which results in severe pain and impaired joint function. However, the mechanisms are not well understood. Circular RNAs (circRNAs) are reported to have various biological functions and participate in the development, diagnosis, prognosis, and treatment of different diseases. This study aimed to investigate the roles and mechanisms of circ-slain2 in TMJOA. We first established TMJOA mouse models and found circ-slain2 was lowly expressed in the cartilage of TMJOA through sequencing data. We observed that circ-slain2 is predominantly localized in the cytoplasm and downregulated in mouse condylar chondrocytes (mCCs) treated with tumor necrosis factor α (TNFα) and interferon γ (IFNγ). Micro–computed tomography and histological examination showed that intra-articular injection of circ-slain2 overexpressing adeno-associated virus could alleviate cartilage catabolism and synovial inflammation to relieve TMJOA in vivo. In addition, elevated circ-slain2 also showed anticatabolic and anti-inflammatory effects on IFNγ- and TNFα-stimulated mouse condylar chondrocytes (mCCs). Functional enrichment analysis indicated that protein processing in endoplasmic reticulum (ER) was associated with TMJOA, and further functional experiments confirmed that circ-slain2 could suppress ER stress in OA mCCs. RNA binding protein immunoprecipitation assay revealed an overt interaction between activating transcription factor 6 (ATF6) and circ-slain2. Inhibition of the expression of both ATF6 and circ-slain2 resulted in dilation of the ER and enhanced the expression of ER stress markers, whose ER stress level was higher than inhibition of ATF6 but lower than knockdown of circ-slain2 expression. Collectively, our research demonstrated that circ-slain2 could regulate ATF6 to relieve ER stress, reducing temporomandibular joint cartilage degradation and synovial inflammation. These findings provide prospects for developing novel osteoarthritis therapies based on circ-slain2 by focusing on reducing the inflammation of synovium and the imbalance between matrix synthesis and degradation.
Factors impacting the demonstration of relational autonomy in medical decision-making: A meta-synthesis
Authors: Le Thi Dung , Lin Shih-Chun , Huang Mei-Chih , Fan Sheng-Yu , Kao Chi-Yin
Published: October 2023

Background

Relational autonomy is an alternative concept of autonomy in which an individual is recognized as embedded into society and influenced by relational factors. Social context, including social location, political structure, and social forces, significantly influence an agent to develop and exercise autonomy skills. The relational approach has been applied in clinical practice to identify relational factors impacting patient autonomy and decision-making, yet there is a knowledge gap in how these factors influence the demonstration of relational autonomy in the context of medical decisions of adults.

Objective

The present study targeted the existing knowledge of what and how relational factors impact individuals making medical decisions using the theoretical framework of relational autonomy.

Methods

A meta-synthesis study was utilized. Four electronic databases, including Embase, OVID Medline, CINAHL, and PubMed, were searched, along with gray literature and reference lists, to identify relevant studies.

Results

23 studies reporting 21 qualitative and two mixed-method studies were reviewed. Four themes emerged from the qualitative findings: (1) supportive relationships facilitate an individual’s relational autonomy; (2) obtaining comprehensive information from broader sources helps individuals exercise relational autonomy; (3) undue family pressure impedes the exercising of patient relational autonomy; and (4) healthcare providers’ dominant voice hampers the demonstration of relational autonomy.

Conclusions

Applying relational autonomy to assist adults in making well-considered decisions is essential. The meta-synthesis suggests establishing a supportive relationship between individuals, healthcare providers, and family. A supportive relationship will allow healthcare providers to make judgments in line with an individual’s values and wishes with the aim of promoting relational autonomy. Advance care planning was proposed as the effective solution to obtain a consensus between individuals and their families while respecting an individual’s values and preferences. Furthermore, it is considered crucial for healthcare providers to appreciate an individual's values and incorporate their preferences into recommendations.
Trauma-Informed PBIS: How Educators Can Combine Evidence-Based Practices for Behavior Management With Trauma-Informed Care
Authors: Riggs Leah , Landrum Timothy
Published: October 2023

Overwhelming events such as neglect, abuse, and violence impact students in a number of ways. Typically, students who have experienced trauma demonstrate significant deficits in skills that promote emotional and behavioral regulation. When these deficits are displayed in the classroom, learning can be significantly disrupted for the survivor and also for his or her peers. Research shows that using evidence-based practices (EBPs) for managing challenging classroom behavior is the most efficient approach to improving outcomes for students. Positive behavioral interventions and supports (PBIS) is a well-researched, multi-tiered framework for behavioral support that has been used in many districts throughout the United States for over 30 years. Many EBPs for classroom behavior management fit well within the framework of PBIS, allowing educators to systematically implement the strategies and use the data they collect for decision-making. This article outlines specific EBPs that fit within the PBIS multi-tiered model and highlights how these examples of sound classroom and behavior management are a cornerstone of a trauma-informed classroom.
Anti-Aging of the Nervous System and Related Neurodegenerative Diseases With Chinese Herbal Medicine
Authors: Du Xiaohui , Lou Nanbin , Hu Sinan , Xiao Ruopeng , Chu Chu , Huang Qiankai , Lu Lin , Li Shanshan , Yang Jing
Published: October 2023

Human beings have always pursued a prolonged lifespan, while the aging of the nervous system is associated with a large variety of diseases. Pathological aging of the nervous system results in a series of neurodegenerative diseases and can cause disability and death in the elderly. Therefore, there is an urgent need for the prevention and treatment of nervous system aging. Chinese herbal medicines have a long history, featuring rich and safe ingredients, and have great potential for the development of anti-aging treatment. We searched the publications on PubMed with key words “anti-aging of the nervous system” and “Chinese herbal medicine” in recent 10 years, and found sixteen Chinese herbal medicines. Then by comparing their popularity of use as well as active components based on the research articles, five common Chinese herbal medicines namely Ginseng Radix, Lycii Fructus, Astragali Radix, Coptidis Rhizoma and Ginkgo Folium, were confirmed to be the most related to anti-nervous system aging and neural degenerative diseases. At the same time, the active ingredients, research models, action mechanisms and curative effects of these five common Chinese herbal medicines were reviewed. From the five common Chinese herbal medicines reviewed in this paper, many encouraging effects of Chinese herbal medicines on treating nervous system aging and related diseases were revealed and more potent herbs would be explored with the help of the proposed possible mechanisms.
Learning through interdisciplinary dialogue: Methodological approaches for bridging epistemological divides
Authors: Brown Eleanor , Kirshner Joshua , Dunlop Lynda , Friend Richard , Brooks Sally , Redeker Kelly , Zimmermann Ana , H Walton Paul , Cairo João , Veneu Fernanda
Published: October 2023

Scientific innovations for sustainable development often make huge promises about overcoming climate change, or promote technological innovations that have potential development implications. However, the social outcomes of such interventions are often considered superficially; thus potentially reinforcing injustices or producing unforeseen, undesirable outcomes. Increasingly, projects claim to have an interdisciplinary dimension, but processes of interdisciplinary dialogue can be difficult to maintain. This means that researchers have to be prepared to engage in potentially extensive, transformative dialogue and be willing to learn from the disciplinary knowledge of the other. This can be methodologically challenging both for natural and social scientists. This paper reports meta-research exploring the methodological processes and learning experiences of academics involved in research on the implementation of second-generation biofuel technology. Through interdisciplinary meetings, workshops, reflections and interviews we built up sustainable relationships and bridged epistemological divides. Our approach to interdisciplinary dialogue offers insights into the methodological challenges of interdisciplinary work. We used the framework of transformative learning theory to identify key aspects of the interdisciplinary process and reflected on the need for sustained and open opportunities for dialogue in order to find genuine ways to communicate across disciplines. We explicitly revealed and considered our taken-for-granted assumptions to identify what we understood by key terms and processes, including ‘sustainable’, ‘development’, ‘methodology’, ‘truth’, ‘marginal land’ and ‘outputs’. We found these encounters created opportunities to influence the trajectory of each other’s research and thinking, with the ideal of social and environmental justice prominent in all our discussions. It was through ongoing learning and dialogue that we found that the multifaceted challenges of sustainable development research can become more open, more critical and more able to reveal appropriate solutions and promote relevant ongoing scientific research. This interplay between disciplines is an innovative way to influence decision-making directly.