bluuebunny/crossref_metadata_2025 huggingface dataset:
Anterior cervical discectomy and fusion with a zero-profile VA spacer device: a clinical and radiological study with two-year follow-up
Authors: Zhao Hai-Hong , Xu Hao-Wei , Wang Shan-Jin , Hu Tao , Wu De-Sheng
Published: January 2024

Study design

A retrospective study.

Objective

The aim of this study was to compare clinical and radiological outcomes of the anterior cervical discectomy and fusion (ACDF) with a novel zero-profile variable-angle (Zero-P VA) spacer and a traditional poly-ether-ether-ketone (PEEK) cage and plate system in cases pertaining to cervical radiculopathy/myelopathy.

Summary of background data

There are two conventional types of ACDF procedures aimed at treating symptomatic cervical spondylosis. The first one involves an uninstrumented “stand-alone” approach utilizing bone graft/cage, while the second incorporates bone graft/cage in conjunction with a front plate positioned before the vertebral bodies. Both procedures have their own inherent advantages and disadvantages. The Zero-P VA spacer, however, represents a unique synthesis by amalgamating the advantages of both traditionally typical procedures. Notably, this spacer can potentially circumvent the issue related to prevertebral soft-tissue disturbance and reduce the occurrence of dysphagia.

Methods

Using our surgical database, the authors systematically conducted a retrospective analysis encompassing all patients who underwent single-level ACDF between January 2018 and January 2019, with a minimum two-year follow-up. Patients either received a Zero-P VA implant or PEEK cage coupled with plating. The Japanese Orthopedic Association (JOA) score and Visual Analogue Scale (VAS) for arm and neck pain were documented. Dysphagia was evaluated using the Eating Assessment Tool-10 (ETA-10). Additional parameters such as cervical alignment, fusion rate and the incidence of postoperative complications were assessed.

Results

According to the outcomes of the statistical analysis, there was no substantial disparity that emerged in the advancements observed in the JOA and VAS metrics between the two study cohorts. Noteworthy, however, the ETA-10 scores were statistically significantly reduced in the Zero-P VA group compared to the cage and plating group (p < 0.05). At the final follow-up, there were no statistically significant differences in the height of the operated segment, Cobb angle of the fused segment, C2–C7 Cobb angle and fusion rate between the two groups (p > 0.05). However, postoperative complications were slightly lower in patients with the Zero-P VA group (7.69%) as compared to the cage and plating group (16.67%).

Conclusion

The clinical outcomes observed with the Zero-P VA spacer used for single-level ACDF were found to be satisfactory. The performance of this device is comparable or even superior to the traditional cage and plating method in preventing postoperative dysphagia and mitigating potential complications associated with the use of a plate.
PHB2 promotes SHIP2 ubiquitination via the E3 ligase NEDD4 to regulate AKT signaling in gastric cancer
Authors: Xu Liang , Xiang Wanying , Yang Jiezhen , Gao Jing , Wang Xinyue , Meng Li , Ye Kaihong , Zhao Xiao Hong , Zhang Xu Dong , Jin Lei , Ye Yan
Published: January 2024

Background

Prohibitin 2 (PHB2) exhibits opposite functions of promoting or inhibiting tumour across various cancer types. In this study, we aim to investigate its functions and underlying mechanisms in the context of gastric cancer (GC).

Methods

PHB2 protein expression levels in GC and normal tissues were examined using western blot and immunohistochemistry. PHB2 expression level associations with patient outcomes were examined through Kaplan–Meier plotter analysis utilizing GEO datasets (GSE14210 and GSE29272). The biological role of PHB2 and its subsequent regulatory mechanisms were elucidated in vitro and in vivo. GC cell viability and proliferation were assessed using MTT cell viability analysis, clonogenic assays, and BrdU incorporation assays, while the growth of GC xenografted tumours was measured via IHC staining of Ki67. The interaction among PHB2 and SHIP2, as well as between SHIP2 and NEDD4, was identified through co-immunoprecipitation, GST pull-down assays, and deletion-mapping experiments. SHIP2 ubiquitination and degradation were assessed using cycloheximide treatment, plasmid transfection and co-immunoprecipitation, followed by western blot analysis.

Results

Our analysis revealed a substantial increase in PHB2 expression in GC tissues compared to adjacent normal tissues. Notably, higher PHB2 levels correlated with poorer patient outcomes, suggesting its clinical relevance. Functionally, silencing PHB2 in GC cells significantly reduced cell proliferation and retarded GC tumour growth, whereas overexpression of PHB2 further enhanced GC cell proliferation. Mechanistically, PHB2 physically interacted with Src homology 2-containing inositol 5-phosphatase 2 (SHIP2) in the cytoplasm of GC cells, thus leading to SHIP2 degradation via its novel E3 ligase NEDD4. It subsequently activated the PI3K/Akt signaling pathway and thus promoted GC cell proliferation.

Conclusions

Our findings highlight the importance of PHB2 upregulation in driving GC progression and its association with adverse patient outcomes. Understanding the functional impact of PHB2 on GC growth contributes valuable insights into the molecular underpinnings of GC and may pave the way for the development of targeted therapies to improve patient outcomes.
Effects of finerenone and glucagon-like peptide 1 receptor agonists on cardiovascular and renal outcomes in type 2 diabetes mellitus: a systematic review and meta-analysis
Authors: Gu Xia , Jiang Shimin , Yang Yue , Li Wenge
Published: January 2024

Objective

To assess the effects of finerenone and glucagon-like peptide 1 receptor agonists (GLP1-RA) on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus (T2DM), and the relative cardiovascular benefits in patients with or without established atherosclerotic cardiovascular disease for different outcomes with these classes of drugs.

Methods

We searched PubMed, the Cochrane Library, and Embase from January 1, 2000, to December 30, 2022, to identify randomized controlled trials. The primary outcomes were the composite of nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death (MACE); hospitalization for heart failure (HHF); and a composite of renal outcomes. The results were reported as hazard ratios (HRs) with 95% confidence intervals (CIs).

Results

In total, we identified 11 trials and 73,927 participants, 13,847 (18.7%) in finerenone trials and 60,080 (81.3%) in GLP1-RA trials. Finerenone reduced the risk of MACE by 13% (HR, 0.87; 95% CI, 0.79–0.95; P = 0.003), while GLP1-RA reduced the risk in a similar magnitude by 13% (HR, 0.87; 95% CI, 0.83–0.92; P < 0.001). For both drug classes, the effect on lowering the risk of MACE was restricted to approximately 14% in patients with established atherosclerotic cardiovascular disease (HR, 0.86; 95% CI, 0.82–0.90; P < 0.001), whereas no effect was observed in patients without established atherosclerotic cardiovascular disease (HR, 0.93; 95% CI, 0.85–1.02; P = 0.12). GLP1-RA reduced myocardial infarction, stroke and cardiovascular death more than finerenone (which appeared to have no effect). Only finerenone was beneficial for reducing the risk of HHF (HR, 0.78; 95% CI, 0.66–0.92; P = 0.003). Both finerenone (HR, 0.84; 95% CI, 0.77–0.92; P < 0.001) and GLP1-RA (HR, 0.81; 95% CI, 0.76–0.86; P < 0.001) reduced the risk of kidney disease progression, including macroalbuminuria, and finerenone was superior to GLP1-RA in delaying deterioration of kidney function.

Conclusions

Finerenone and GLP1-RA lead to a risk reduction in MACE to a similar degree in patients with established atherosclerotic cardiovascular disease. For both drug classes, the effect on lowering the risk of progression of kidney disease was also in a similar magnitude in patients with T2DM, whereas only finerenone had a significant protective effect against HHF. Treatment decisions for patients with T2DM should consider the clinical benefit profiles of each drug.
Is bladder outlet obstruction rat model to induce overactive bladder (OAB) has similarity to human OAB? Research on the events in smooth muscle, collagen, interstitial cell and telocyte distribution
Authors: Wishahi Mohamed , Hassan Sarah , Kamal Nabawya , Badawy Mohamed , Hafiz Ehab
Published: January 2024

Background

Cellular and cytoskeletal events of overactive bladder (OAB) have not been sufficiently explored in human bladder due to different limitations. Bladder outlet obstruction (BOO) had been induced in different animal models with different methods to induce (OAB). Similarity of the animal models of BOO to the human OAB is postulated but has not been confirmed. The interstitial cells of Cajal (ICCs), and telocytes (TCs) are an important players in smooth muscles conductivity, they had not been well investigated in the previous BOO models. Objectives are to investigate the morphological pattern of cellular, cytoskeleton and telocytes distribution in BOO rat model and to match the events in two time periods and compare it to the findings in real-world human OAB.

Methods

Female Sprague-Dawley rats (Rattus norvegicus) were randomly divided into: sham (n = 10), BOO 6 W (n = 10), BOO 8 W (n = 10). Operative procedure to Induce BOO was done under anesthesia with intraperitoneal Ketamine administration. The Effect of induction of BOO was evaluated after 6 and 8 weeks. The rats were anesthetized, and the urinary bladder was removed, while the rat was unconscious under anaesthesia it was transferred to the inhalation anaesthesia cage for euthanasia, rats were sacrificed under light anesthesia using isoflurane. Care of animals, surgical procedure, and euthanasia adhered to Guide for the Care and Use of Laboratory Animals, and AVMA Guidelines for the Euthanasia of Animals. The retrieved bladder was processed for examination with histopathology, immunohistochemistry (IHC), and transmission electron microscopy (EM).

Results

Histological examination of the bladder shows thinner urothelium, condensation of collagen between muscle bundles. IHC with c-kit shows the excess distribution of ICCs between smooth muscle bundles. EM shows frequent distribution of TCs that were situated between collagen fibers. Finings in BOO 6 W group and BOO 8 W group were comparable.

Conclusion

The animal model study demonstrated increased collagen/ smooth muscle ratio, high intensity of ICCs and presence of TCs. Findings show that a minimally invasive procedure to induce BOO in rats had resulted in an OAB that has morphological changes that were stable in 6 & 8 weeks. We demonstrated the distribution of TCs and ICCs in the rat animal model and defined them. The population of TCs in the BOO rat model is described for the first time, suggests that the TCs and ICCs may contribute to the pathophysiology of OAB. Similarity of animal model to human events OAB was demonstrated. These findings warrant further study to define the role of TCs in OAB.

Clinical trial registry

The study does not require a clinical trial registration; it is an experimental animal study in basic science and does not include human subjects.
Conversion surgery for initially unresectable locally advanced pancreatic ductal adenocarcinoma after chemotherapy followed by carbon-ion radiotherapy: a case report
Authors: Watanabe Yusuke , Tatsuguchi Takaaki , Date Kenjiro , Shinkawa Tomohiko , Kuga Hirotaka , Tamiya Sadafumi , Nishihara Kazuyoshi , Nakano Toru
Published: January 2024

Background

Recent advances in chemotherapy and chemoradiotherapy have enabled conversion surgery (CS) to be performed for selected patients with initially unresectable locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC). Many studies indicate CS might extend the survival of patients with initially unresectable LA PDAC. However, several clinical questions concerning CS remain, such as the optimal preoperative treatment. Carbon-ion radiotherapy (CIRT) is a unique radiotherapy that offers higher biological effectiveness than conventional radiotherapy. Here, we report a long-term survival case with initially unresectable LA PDAC who underwent CS after chemotherapy followed by CIRT.

Case presentation

The patient was a 72-year-old Japanese woman with unresectable LA pancreatic head cancer with tumor contact to the superior mesenteric artery (SMA). She underwent four courses of chemotherapy (gemcitabine plus nanoparticle albumin-bound paclitaxel). However, the lesion did not shrink and tumor contact with the SMA did not improve after chemotherapy. Because the probability of achieving curative resection was judged to be low, she underwent radical dose CIRT, and chemotherapy was continued. She complained of vomiting 2 months after CIRT. Although imaging studies showed no tumor growth or metastasis, a duodenal obstruction which was speculated to be an adverse effect of CIRT was observed. She could not eat solid food and a trans-nasal feeding tube was inserted. Therapeutic intervention was required to enable enteral nutrition. We proposed several treatment options. She chose resection with the expectation of an anti-tumor effect of chemotherapy and CIRT rather than course observation with tube feeding or bypass surgery. Therefore, subtotal-stomach-preserving pancreatoduodenectomy with portal vein resection was performed as CS. Pathological examination of the resected specimen revealed an R0 resection with a histological response of Evans grade IIA. Postoperatively, she recovered uneventfully. Adjuvant chemotherapy with tegafur/gimeracil/oteracil (S1) was administrated. At the time of this report, 5 years have passed since the initial consultation and she has experienced no tumor recurrence.

Conclusions

The present case suggests that multidisciplinary treatment consisting of a combination of recent chemotherapy and CIRT may be beneficial for unresectable LA PDAC. However, further studies are required to assess the true efficacy of this treatment strategy.
Cobdock: an accurate and practical machine learning-based consensus blind docking method
Authors: Ugurlu Sadettin Y. , McDonald David , Lei Huangshu , Jones Alan M. , Li Shu , Tong Henry Y. , Butler Mark S. , He Shan
Published: January 2024

Probing the surface of proteins to predict the binding site and binding affinity for a given small molecule is a critical but challenging task in drug discovery. Blind docking addresses this issue by performing docking on binding regions randomly sampled from the entire protein surface. However, compared with local docking, blind docking is less accurate and reliable because the docking space is too largetly sampled. Cavity detection-guided blind docking methods improved the accuracy by using cavity detection (also known as binding site detection) tools to guide the docking procedure. However, it is worth noting that the performance of these methods heavily relies on the quality of the cavity detection tool. This constraint, namely the dependence on a single cavity detection tool, significantly impacts the overall performance of cavity detection-guided methods. To overcome this limitation, we proposed Consensus Blind Dock (CoBDock), a novel blind, parallel docking method that uses machine learning algorithms to integrate docking and cavity detection results to improve not only binding site identification but also pose prediction accuracy. Our experiments on several datasets, including PDBBind 2020, ADS, MTi, DUD-E, and CASF-2016, showed that CoBDock has better binding site and binding mode performance than other state-of-the-art cavity detector tools and blind docking methods.
Neural electric bass guitar synthesis framework enabling attack-sustain-representation-based technique control
Authors: Koguchi Junya , Morise Masanori
Published: January 2024

Musical instrument sound synthesis (MISS) often utilizes a text-to-speech framework because of its similarity to speech in terms of generating sounds from symbols. Moreover, a plucked string instrument, such as electric bass guitar (EBG), shares acoustical similarities with speech. We propose an attack-sustain (AS) representation of the playing technique to take advantage of this similarity. The AS representation treats the attack segment as an unvoiced consonant and the sustain segment as a voiced vowel. In addition, we propose a MISS framework for an EBG that can control its playing techniques: (1) we constructed a EBG sound database containing a rich set of playing techniques, (2) we developed a dynamic time warping and timbre conversion to align the sounds and AS labels, (3) we extend an existing MISS framework to control playing techniques using AS representation as control symbols. The experimental evaluation suggests that our AS representation effectively controls the playing techniques and improves the naturalness of the synthetic sound.
The role of City Climate Networks in Promoting Citizen Participation in Municipalities: A Critical Multi-Case Analysis
Authors: Zapata Arango Mateo , Hoppe Thomas , Itten Anatol , Blok Kornelis
Published: January 2024

Background

At the COP21, cities were recognised as key actors in combatting climate change. In supporting cities, climate city networks such as transnational climate networks (TCNs) and national climate networks (NCNs) have emerged to enable cities in building capacities and formulating climate policy whilst also encouraging citizen engagement and participation in public decision-making. This paper addresses the question whether and how TCN or NCN membership enables municipalities to implement citizen participation in public decision-making. Six propositions are presented addressing: presumed influence of TCN membership on citizen participation, organization of citizen participation, initiator capacity, goal setting, involvement of stakeholders, participatory methods used, and planning processes. A multi-case study research design is used to verify these propositions, comprising of four medium-sized cities in the Netherlands and three in Belgium.

Results

Results of the analysis of four cities in The Netherlands show that municipalities having membership to climate city networks only to a low extent empower citizen participation via local climate agendas. Citizen participation emerges rather bottom-up via local initiatives or capacity building via EU framework programs—outside TCNs or NCNs—that better suit financial needs and provide more immediate benefits to municipalities. None of the six propositions were confirmed. A more positive image resulted from the Belgian cases that moderately confirmed four out of six propositions (i.e., organizing citizen participation, goal setting, selection of methods, and planning), and featured indirect empowerment via externally funded implementation projects following firm integration of participation in local climate policy through TCN influence.

Conclusions

In terms of citizen participation selected municipalities in the Netherlands having TCN and/or NCN membership only to a small extent differ from those not having membership. This is partly due to poor implementation of TCNs and NCNs—with Covenant of Mayors and ‘Klimaatverbond’ lacking support structure and capacity—having lost importance during the past years. However, there is reason to believe that context makes a difference as revealed by the cases from Belgium, which revealed more positive results.
Longitudinal associations between community violence exposure, posttraumatic stress symptoms, and eating disorder symptoms
Authors: Isaksson Martina , Isaksson Johan , Schwab-Stone Mary , Ruchkin Vladislav
Published: January 2024

Background

Eating disorder (ED) symptoms have been associated with different types of traumatic events, such as exposure to sexual and physical violence, and emotional abuse. However, the relation between ED symptoms and community violence exposure (CVE) is underexplored, despite the latter’s adverse effects on many aspects of adolescent functioning. The primary aim of this study was to evaluate the relation between CVE and ED symptoms in adolescents, while also investigating the potential mediating and moderating roles of posttraumatic stress (PTS) symptoms, gender, and ethnicity.

Methods

Data were collected longitudinally over two consecutive years in the city of New Haven, CT, in the United States. Participants were 2612 adolescent students from the public school system (1397 girls and 1215 boys) with an average age of 12.8 years (SD = 1.29). The students were comprised of several different ethnic groups, including Caucasians, African Americans and Hispanic Americans. Associations between CVE (no exposure, witnessing, and victimization) and PTS symptoms at year one, and ED symptoms (thoughts and compensatory behaviors) at year two, were assessed with self-rating instruments. Moderation and mediation analyses were conducted using a variant of linear regression (Hayes PROCESS macro).

Results

ED symptoms at year two were significantly associated with both witnessing and being a victim of community violence at year one, with most or all of the relations being explained by PTS symptoms. Overall, neither gender nor ethnicity had a meaningful moderating effect in the observed relations.

Conclusions

The findings support the notion that assessing and addressing PTS symptoms might be beneficial when treating individuals with ED symptoms who have experienced community violence, irrespective of gender or ethnicity.
Successful surgical treatment of an intraoperatively ruptured lung abscess rupture using free pericardial fat implantation: a case report
Authors: Iijima Yoshihito , Mizoguchi Takaki , Ishikawa Masahito , Iwai Shun , Motono Nozomu , Uramoto Hidetaka
Published: January 2024

Background

Lung abscess treatment results the treatment results improved with the development of antibiotics; however, surgical treatment is indicated when pyothorax is present, surgical treatment is indicated. When a lung abscess ruptures, pyothorax and fistula occur, which are difficult to treat.

Case presentation

A 74-year-old woman who experienced exacerbated dyspnea and left back pain for 10 days was diagnosed with a lung abscess caused by an odontogenic infection. The patient’s medical history included hypertension, angina pectoris, untreated dental caries, and periodontitis. Despite administration of meropenem for 5 days, inflammatory markers increased. Chest radiography revealed pleural effusion exacerbation; therefore, the patient immediately underwent chest drainage and surgery was planned. Thoracic debridement and parietal and visceral decortication were performed. However, the lung abscess in the lateral basal segment ruptured during visceral decortication. As the tissue was fragile and difficult to close with sutures, free pericardial fat was implanted in the ruptured abscess cavity and fixed with fibrin glue, and sutured to the abscess wall. No signs of postoperative air leakage or infection of the implanted pericardial fat were observed. All drainage tubes were removed by postoperative day 9. The patient was discharged on postoperative day 12 and underwent careful observation during follow-up as an outpatient. At 1 year and 2 months after surgery, empyema recurrence was not observed.

Conclusions

A lung abscess that ruptured intraoperatively was successfully and effectively treated by implantation of free pericardial fat in the abscess cavity.
The evolution of acute stroke care in Germany from 2019 to 2021: analysis of nation-wide administrative datasets
Authors: Ungerer Matthias N. , Bartig Dirk , Richter Daniel , Krogias Christos , Hacke Werner , Gumbinger Christoph
Published: January 2024

Background

The treatment of ischemic stroke (IS) has changed considerably in recent years. Particularly the advent of mechanical thrombectomy (MTE) has revolutionized the available treatment options. Most patients in developed countries have access to intravenous thrombolysis (IVT). However access to MTE remains restricted in some regions despite efforts to increase its availability. We performed an evaluation of national datasets to monitor improvements made in access to revascularization therapies for IS patients in Germany.

Methods

We analyzed national datasets on German Diagnosis-Related Groups and structured quality reports by extracting information of patients admitted with stroke with and without IVT and MTE for the period of 2019–2021. Data from 2016 and limited data for 2022 were also included for comparison.

Results

Admissions with ischemic stroke declined during the years of the COVID 19 pandemic by 4.5% from 227,258 in 2019 to 216,923 in 2021. IVT rates were stable with 16.3% being treated with IVT in 2019 and 2021. MTE rates continued to increase from 7.1 to 8.4% and the number of MTE centers increased by 14.8% in the same period. Over 87.3% of MTEs were performed in centers with a case volume exceeding 50 cases per year in 2021. The largest increase in the relative share of MTEs was seen in large MTE centers (n ≥ 200). Patient age for MTEs surpassed the age for IVTs in 2019 and the proportion of patients ≥ 80 years receiving MTE continued to increase. The proportion of regions in Germany with poor MTE rates (≤ 4.1%) decreased significantly from 2019 (12.3%) to 2021 (5.3%) (p < 0.001).

Conclusions

We found strong evidence that while IVT rates reached a temporary ceiling effect, both the absolute number of and access to MTEs continued to increase in Germany. Regional disparities have become less significant and the majority of MTEs are performed in centers with medium or high case volumes.
FpOGT is required for fungal growth, stress response, and virulence of Fusarium proliferatum by affecting the expression of glucokinase and other glucose metabolism-related genes
Authors: Gao Yizhou , Wang Yitong , He Siming , Li Haibo , Wang Yuqing , Wu Zhihong
Published: January 2024

O-GlcNAcylation, an important post-translational modification catalyzed by O-GlcNAc transferase (OGT), plays critical roles in several biological processes. In this study, we present our findings on the function of FpOGT in regulating physiological processes and pathogenicity of Fusarium proliferatum (Fp), the alfalfa root rot fungus. The deletion of FpOGT impaired mycelial growth and altered macroconidia morphology in Fp. Furthermore, ΔFpOGT mutant displayed altered tolerance to various stressors, including cell wall perturbing agents, osmotic stressors, metal ionic stressors, and fungicides. Deletion of FpOGT significantly decreased Fp virulence toward alfalfa. The transcriptome analysis demonstrated that FpOGT plays a regulatory role in glucose metabolic pathways, including glycolysis, tricarboxylic acid (TCA) cycle, and hexosamine biosynthesis pathway (HBP), by influencing the expression of relevant genes. The downregulation of the glucokinase gene, FpGCK, was observed in ΔFpOGT, and the disruption of FpGCK led to a decrease in Fp virulence. Additionally, FpOGT affected the expression levels of the FpGCK-AS1 isoform, thereby impacting glucokinase function. The molecular docking analysis elucidated the plausible physical interaction between FpOGT and FpGCK, thereby offering valuable insights into their interrelationship. These findings underscore the indispensable involvement of FpOGT, the sole O-GlcNAc transferase in Fp, in various biological processes and the pathogenicity through its regulation of fundamental metabolic processes. Consequently, this study emphasizes the significance and elucidates the molecular mechanism underlying the role of O-GlcNAc transferase in diverse fundamental biological processes and the pathogenicity of phytopathogenic fungi.
Update on Biomarkers in Renal Cell Carcinoma
Authors: Saliby Renée M. , Saad Eddy , Kashima Soki , Schoenfeld David A. , Braun David A.
Published: January 2024

Immune checkpoint inhibitors have significantly transformed the treatment paradigm for metastatic renal cell carcinoma (RCC), offering prolonged overall survival and achieving remarkable deep and durable responses. However, given the multiple ICI-containing, standard-of-care regimens approved for RCC, identifying biomarkers that predict therapeutic response and resistance is of critical importance. Although tumor-intrinsic features such as pathological characteristics, genomic alterations, and transcriptional signatures have been extensively investigated, they have yet to provide definitive, robust predictive biomarkers. Current research is exploring host factors through in-depth characterization of the immune system. Additionally, innovative technological approaches are being developed to overcome challenges presented by existing techniques, such as tumor heterogeneity. Promising avenues in biomarker discovery include the study of the microbiome, radiomics, and spatial transcriptomics.
Improved Cardiomyopathy Risk Prediction Using Global Longitudinal Strain and N-Terminal-Pro-B-Type Natriuretic Peptide in Survivors of Childhood Cancer Exposed to Cardiotoxic Therapy
Authors: Ehrhardt Matthew J. , Liu Qi , Mulrooney Daniel A. , Rhea Isaac B. , Dixon Stephanie B. , Lucas John T. , Sapkota Yadav , Shelton Kyla , Ness Kirsten K. , Srivastava Deo Kumar , McDonald Aaron , Robison Leslie L. , Hudson Melissa M. , Yasui Yutaka , Armstrong Gregory T.
Published: January 2024

PURPOSE

To leverage baseline global longitudinal strain (GLS) and N-terminal-pro-B-type natriuretic peptide (NT-proBNP) to identify childhood cancer survivors with a normal left ventricular ejection fraction (LVEF) at highest risk of future treatment-related cardiomyopathy.

METHODS

St Jude Lifetime Cohort participants ≥5 years from diagnosis, at increased risk for cardiomyopathy per the International Guideline Harmonization Group (IGHG), with an LVEF ≥50% on baseline echocardiography (n = 1,483) underwent measurement of GLS (n = 1,483) and NT-proBNP (n = 1,052; 71%). Multivariable Cox regression models estimated hazard ratios (HRs) and 95% CIs for postbaseline cardiomyopathy (modified Common Terminology Criteria for Adverse Events ≥grade 2) incidence in association with echocardiogram-based GLS (≥–18) and/or NT-proBNP (>age-sex-specific 97.5th percentiles). Prediction performance was assessed using AUC in models with and without GLS and NT-proBNP and compared using DeLong's test for IGHG moderate- and high-risk individuals treated with anthracyclines.

RESULTS

Among survivors (median age, 37.6; range, 10.2-70.4 years), 162 (11.1%) developed ≥grade 2 cardiomyopathy 5.1 (0.7-10.0) years from baseline assessment. The 5-year cumulative incidence of cardiomyopathy for survivors with and without abnormal GLS was, respectively, 7.3% (95% CI, 4.7 to 9.9) versus 4.4% (95% CI, 3.0 to 5.7) and abnormal NT-proBNP was 9.9% (95% CI, 5.8 to 14.1) versus 4.7% (95% CI, 3.2 to 6.2). Among survivors with a normal LVEF, abnormal baseline GLS and NT-proBNP identified anthracycline-exposed, IGHG-defined moderate-/high-risk survivors at a four-fold increased hazard of postbaseline cardiomyopathy (HR, 4.39 [95% CI, 2.46 to 7.83]; P < .001), increasing to a HR of 14.16 (95% CI, 6.45 to 31.08; P < .001) among survivors who received ≥250 mg/m2 of anthracyclines. Six years after baseline, AUCs for individual risk prediction were 0.70 for models with and 0.63 for models without GLS and NT-proBNP ( P = .022).

CONCLUSION

GLS and NT-proBNP should be considered for improved identification of survivors at high risk for future cardiomyopathy.
Implementing a Patient-Reported Outcome Dashboard in Oncology Telemedicine Encounters: Clinician and Patient Adoption and Acceptability
Authors: Mohindra Nisha A. , Coughlin Ava , Kircher Sheetal , O'Daniel Alesia , Barnard Cynthia , Cameron Kenzie A. , Hirschhorn Lisa R. , Cella David
Published: January 2024

PURPOSE

Telemedicine provides numerous benefits to patients, yet effective communication and symptom assessment remain a concern. The recent uptake of telemedicine provided an opportunity to use a newly developed dashboard with patient-reported outcome (PRO) information to enhance communication and shared decision making (SDM) during telemedicine appointments. The objective of this study was to identify barriers to using the dashboard during telemedicine, develop implementation strategies to address barriers, and pilot test use of this dashboard during telemedicine appointments in two practice settings to evaluate acceptability, adoption, fidelity, and effectiveness.

METHODS

Patients and clinicians were interviewed to identify determinants to dashboard use in telemedicine. Implementation strategies were designed and refined through iterative feedback from stakeholders. A pilot study of dashboard use was conducted from March to September 2022. Acceptability, adoption, and fidelity were evaluated using mixed methods. SDM was evaluated using the collaboRATE measure.

RESULTS

One hundred two patient encounters were evaluated. Most patients (62; 60%) had completed some PRO data at the time of their telemedicine encounter. Most (82; 80%) encounters had clinician confirmation that PRO data had been reviewed; however, collaborative review of the dashboard was documented in only 27%. Degree of SDM was high (mean collaboRATE score 3.40; SD, 0.11 [95% CI, 3.17 to 3.63] out of a maximum score of 4). Implementation strategies focused on patient engagement, education, and remote PRO completion. Clinician-facing strategies included education, practice facilitation, and small tests of change.

CONCLUSION

This study demonstrated that implementation of a PRO-based dashboard into telemedicine appointments was feasible and had acceptable adoption and acceptability by patients and clinicians when several strategies were used to engage end users. Strategies targeting both patients and clinicians are needed to support routine and effective PRO integration in telemedicine.
Genetic Analysis, Phenotypic Spectrum and Functional Study of Rare Osteogenesis Imperfecta Caused by CRTAP Variants
Authors: Zhou Bingna , Gao Peng , Hu Jing , Lin Xiaoyun , Sun Lei , Zhang Qian , Jiang Yan , Wang Ou , Xia Weibo , Xing Xiaoping , Li Mei
Published: January 2024

Objective

Deficiency of cartilage-associated protein (CRTAP) can cause extremely rare autosomal recessive osteogenesis imperfecta (OI) type VII. We investigated the pathogenic mechanisms of CRTAP variants through functional studies on bones of patients with OI.

Methods

Two nonconsanguineous families with CRTAP mutations were included and their phenotypes and genotypes were evaluated. Bone specimens were obtained from 1 patient with OI and a normal control during orthopedic surgery. The impacts of the novel variant on the CRTAP transcript were confirmed. The expression levels of CRTAP mRNA and CRTAP protein were analyzed. The quantification of prolyl 3-hydroxylation in the α1 chain of type I collagen was evaluated.

Results

Patients with OI type VII had early-onset recurrent fractures, severe osteoporosis, and bone deformities. The c.621 + 1G > A and c.1153-3C > G mutations were identified in CRTAP in the patients with OI. The c.621 + 1G > A variant was a novel mutation that could impair mRNA transcription, leading to a truncated CRTAP protein. In a patient with c.621 + 1G > A and c.1153-3C > G mutations in CRTAP, the mRNA and protein levels of CRTAP in osteoblasts were significantly decreased and the osteoid volume and osteoblast numbers were markedly reduced compared with those in the normal control individual. This was simultaneously accompanied by significantly reduced prolyl 3-hydroxylation at Pro986 in the α1 chain of type I collagen and invisible active bone formation in bone.

Conclusion

The novel c.621 + 1G > A mutation in CRTAP expands the genotypic spectrum of type VII OI. Biallelic mutations of c.621 + 1G > A and c.1153-3C > G in CRTAP can lead to reduced CRTAP mRNA and deficient CRTAP protein in osteoblasts, which reduces 3-hydroxylation in Pro986 of the α1 chain of type I collagen and impairs bone formation, thus contributing to severe OI type VII.
Explaining Long COVID: A Pioneer Cross-Sectional Study Supporting the Endocrine Hypothesis
Authors: Ach Taieb , Ben Haj Slama Nassim , Gorchane Asma , Ben Abdelkrim Asma , Garma Meriem , Ben Lasfar Nadia , Bellazreg Foued , Debbabi Widéd , Hachfi Wissem , Chadli Chaieb Molka , Zaouali Monia , Letaief Amel , Ach Koussay
Published: January 2024

Context

In some patients, symptoms may persist after COVID-19, defined as long COVID. Its pathogenesis is still debated and many hypotheses have been raised.

Objective

Our primary objective was to evaluate the corticotroph and somatotroph functions of patients previously infected with SARS-CoV-2 and experiencing post–COVID-19 syndrome to detect any deficiencies that may explain long COVID.

Methods

A cross-sectional study was conducted including patients who had previously contracted SARS-CoV-2 with a postinfection period of 3 months or less to 15 months, divided into 2 groups. The first group (G1) comprised fully recovered patients, while the second group (G2) included patients experiencing long COVID. The primary outcome was the comparison of corticotroph and somatotroph functions.

Results

A total of 64 patients were divided into 2 groups, each consisting of 32 patients. G2 exhibited more frequently anterior pituitary deficits compared to G1 (P = .045): for the corticotroph axis (G1: 6.3% vs G2: 28.1%) and for the somatotroph axis (G1: 31.3% vs G2: 59.4%). Baseline cortisol level was significantly lower in G2 (G1: 13.37 µg/dL vs G2: 11.59 µg/dL) (P = .045). The peak cortisol level was also lower in G2 (G1: 23.60 µg/dL vs G2: 19.14 µg/dL) (P = .01). For the somatotroph axis, the insulin growth factor-1 level was lower in G2 (G1: 146.03 ng/mL vs G2: 132.25 ng/mL) (P = .369). The peak growth hormone level was also lower in G2 (G1: 4.82 ng/mL vs G2: 2.89 ng/mL) (P = .041).

Conclusion

The results showed that long COVID patients in our cohort were more likely to have anterior pituitary deficiencies. The endocrine hypothesis involving anterior pituitary insufficiency can be considered to explain long COVID.
The oscillation of mitotic kinase governs cell cycle latches in mammalian cells
Authors: Dragoi Calin-Mihai , Kaur Ekjot , Barr Alexis R. , Tyson John J. , Novák Béla
Published: January 2024

The mammalian cell cycle alternates between two phases – S-G2-M with high levels of A- and B-type cyclins (CycA and CycB, respectively) bound to cyclin-dependent kinases (CDKs), and G1 with persistent degradation of CycA and CycB by an activated anaphase promoting complex/cyclosome (APC/C) bound to Cdh1 (also known as FZR1 in mammals; denoted APC/C:Cdh1). Because CDKs phosphorylate and inactivate Cdh1, these two phases are mutually exclusive. This ‘toggle switch’ is flipped from G1 to S by cyclin-E bound to a CDK (CycE:CDK), which is not degraded by APC/C:Cdh1, and from M to G1 by Cdc20-bound APC/C (APC/C:Cdc20), which is not inactivated by CycA:CDK or CycB:CDK. After flipping the switch, cyclin E is degraded and APC/C:Cdc20 is inactivated. Combining mathematical modelling with single-cell timelapse imaging, we show that dysregulation of CycB:CDK disrupts strict alternation of the G1-S and M-G1 switches. Inhibition of CycB:CDK results in Cdc20-independent Cdh1 ‘endocycles’, and sustained activity of CycB:CDK drives Cdh1-independent Cdc20 endocycles. Our model provides a mechanistic explanation for how whole-genome doubling can arise, a common event in tumorigenesis that can drive tumour evolution.
Implications of heat exchange for a free-living endangered marsupial determined by non-invasive thermal imaging
Authors: Cooper Christine E. , Withers Philip C.
Published: January 2024

We used thermal imagining and heat balance modelling to examine the thermal ecology of wild mammals, using the diurnal marsupial numbat (Myrmecobius fasciatus) as a model. Body surface temperature was measured using infra-red thermography at environmental wet and dry bulb temperatures of 11.7–29°C and 16.4–49.3°C, respectively; surface temperature varied for different body parts and with environmental temperature. Radiative and convective heat exchange varied markedly with environmental conditions and for various body surfaces reflecting their shapes, surface areas and projected areas. Both the anterior and posterior dorsolateral body areas functioned as thermal windows. Numbats in the shade had lower rates of solar radiative heat gain but non-solar avenues for radiative heat gain were substantial. Radiative gain was higher for black and lower for white stripes, but overall, the stripes had no thermal role. Total heat gain was generally positive (<4 to >20 W) and often greatly exceeded metabolic heat production (3–6 W). Our heat balance model indicates that high environmental heat loads limit foraging in open areas to as little as 10 min and that climate change may extend periods of inactivity, with implications for future conservation and management. We conclude that non-invasive thermal imaging is informative for modelling heat balance of free-living mammals.
Controlling the environment with Artificial Intelligence risks intensifying social inequalities and colonization
Authors: CAMPO RUIZ Ingrid
Published: January 2024

I explore the benefits and shortcomings of including Artificial Intelligence (AI) in environmental governance and remaining within planetary boundaries. AI for the environment should be used with other tools and knowledge such as humanistic, social, and ethical values. AI systems can help mitigate greenhouse gas emissions, ocean acidification, and chemical pollution, safeguard biodiversity, improve water use in agriculture, support vulnerable societies, and combat environmental crimes. AI can efficiently analyze data, monitor, predict and manage natural resources. AI systems does not only describe nature but also active shape by transforming agriculture, fishery, infrastructure, and construction practices. Nevertheless, AI systems enable novel paths for environmental control. The developers from these algorithms commonly originate from prosperous nations, whereas the impact of these algorithms is global. Hence, people with lesser resources and agency are left at a disadvantage to advocate for their interests. These inequalities can result in a new way of colonizing, where wealthier individuals impose their agendas on the rest of the global population. The impact of AI systems on environmental governance is of an unprecedented scale. Ideally, AI systems should adhere to internationally agreed ethical and legal principles.
Problems and Countermeasures to Solve Them in the System of Dance Education in Colleges and Universities in China
Authors: Go Chzhizho
Published: January 2024

The Chinese nation has a unique tradition of choreographic culture, characteristic of the Indochinese region. Consequently, dance is an obligatory phenomenon of culture, in which the aesthetics of the body, emotions and the nature of social relations of the Chinese are harmoniously correlated. It retains its popularity among students of colleges and universities, as it contributes to their comprehensive development. Therefore, dance education in colleges and universities is of great importance for every student and deserves constant development. By the beginning of the 21st century, the Chinese believe that dance education in the country's universities is still in its infancy, and there are many opportunities.

Dance education in universities in China strives to meet international and global standards. And despite this, in China there are many methods and practices for teaching dance art. But there are also many problems, such as focusing on skills, ignoring theory, indoctrinating teaching, and neglecting differences in individual abilities of students and focusing on their harmonious and all-round development.

The traditional technologies of learning and teaching that were present in the 20th century are now perceived as limiting the development of learners and students. Therefore, at the beginning of the 21st century, China began to improve the overall quality of dance teaching, and teachers were asked to reform the classroom and/or classroom regimen to facilitate them and focus on increasing the educational role of dance practices in society.
Las trabajadoras sexuales como colectivo sujeto de acoso y discriminación.
Authors: Fita Ortega Fernando
Published: January 2024

Las trabajadoras sexuales integran un colectivo vulnerable como consecuencia de su estigmatización y el desinterés político y social por quienes desempeñan trabajo sexual. El movimiento abolicionista, fuertemente fortalecido en los últimos años, toma por bandera la erradicación de la prostitución, sin que entre a valorar la situación de quienes ejercen esta actividad. Este escenario ahonda en la vulnerabilidad de las trabajadoras sexuales que, junto al estigma, ya no solamente soportan la invisibilidad a la que se ven sometidas, sino que, además, se ven responsabilizadas de la situación de desigualdad de la mujer en la sociedad. Esta realidad vulnera tanto el espíritu de una sociedad que se define como inspirada en valores sociales y de justicia (art. 1 de la Constitución Española) como las disposiciones, tanto nacionales como internacionales, en materia de no discriminación y acoso.
El reglamento MiCA: responsabilidad y sanción frente al incumplimiento de la regulación del mercado de criptoactivos.
Authors: Pérez Marín María Ángeles
Published: January 2024

Los criptoactivos se han convertido en una vía de financiación dentro del mercado único y, aunque el uso de los mismos es todavía limitado, se espera un exponencial aumento de sus aplicaciones. Incorporan, además, debido a su naturaleza digital, una clara proyección transnacional que es connatural a su naturaleza, que exige la convergencia entre la Unión y otros ordenamientos, órganos y organismos internacionales para prevenir la falta de confianza de los inversores e impedir la inestabilidad que se deriva de las regulaciones hasta ahora existentes. El Reglamento MiCA pretende regular los denominados activos no regulados, clasificándolos en función del riesgo que conlleven e instituye una infraestructura de negociación, que se basa en un régimen sancionador frente al cumplimiento de las obligaciones impuestos a los proveedores de servicios. Es necesario distinguir, no obstante, entre las funciones sancionadoras frente al incumplimiento y la tipificación penal de las conductas.
La Directiva Europea y las Órdenes de Producción y Conservación de pruebas electrónicas en los procesos penales. ¿Nuevas perspectivas?.
Authors: Cuadrado Salinas Carmen
Published: January 2024

Las medidas procesales para obtener y conservar pruebas electrónicas son cada vez más importantes a los efectos de las investigaciones y procesos penales a lo largo de la Unión Europea. Si tenemos en cuenta que los datos electrónicos se almacenan a menudo fuera del Estado investigador, o por un prestador de servicios establecido fuera de dicho Estado, es fácil comprender los enormes problemas que puede generar su obtención. El presente estudio analiza los recientemente aprobados instrumentos legales europeos, diseñados para resolver estos problemas: la Directiva y el Reglamento que contiene las Órdenes europeas de Producción y Conservación de pruebas electrónicas
A ALFABETIZAÇÃO HUMANIZADORA NOS PROCESSOS DE ENSINO E APRENDIZAGEM
Authors: Moreira Elisângela , Siqueira Paula Racelly Bernardo , Cesario Vanessa da Silva , Antônio Gabriel Fábio
Published: January 2024

Este artigo tem como escopo discutir a alfabetização humanizadora nos processos de ensino e de aprendizagem, uma discussão a respeito dos desafios de se ter uma prática pedagógica humanizadora na perspectiva da pedagogia progressista com vistas ao processo de alfabetização. O objetivo geral da investigação é desvelar a caracterização do processo de alfabetização a partir de uma perspectiva humanizadora no contexto de uma abordagem, com base, principalmente, em Paulo Freire, que considere a realidade do educando como referência para a escolha de metodologia de educar. A partir da análise dos dados, pôde-se perceber a importância da prática pedagógica humanizadora nos processos de ensino e de aprendizagem. Assim sendo, foi possível confirmar as contribuições que a pedagogia humanizadora traz para a prática docente, além de sua clareza e intencionalidade de criar condições, instrumentos e meios para superar o individualismo.