bluuebunny/crossref_metadata_2025 huggingface dataset:
Parents' Perceptions About Future Digital Parental Support—A Phenomenographic Interview Study
Authors: Bäckström Caroline , Chamoun Sandi , Tejani Shazima , Larsson Viveca
Published: October 2021

Background: Parents use digital sources (such as the internet or online forums and applications) during pregnancy and after childbirth to receive informative support. Research shows that there is further need for innovation development in digital parental support despite informative support available in digital form.

Purpose: To explore parents' perceptions of future digital parental support concerning pregnancy and the first 18 months of parenthood.

Method: A phenomenographic interview study with an inductive approach including 15 semi-structured interviews was conducted.

Results: The analysis process resulted in three descriptive categories: Opportunities for virtual and in-person meetings, Individualized digital parental support, and Professional knowledge and trustworthiness concerning future digital parental support.

Conclusion: The results broaden the knowledge about how future digital parental support can be designed to facilitate the functional, interactive, and critical digital health literacy of new and would-be parents. To succeed, healthcare organizations should allow healthcare professionals to assume an active role in developing digital parental support, both as health educators (i.e., providing parents with knowledge) and facilitators (i.e., facilitating parents' use of digital parental support). However, parents perceived that future digital parental support should complement standard care instead of replacing in-person meetings with healthcare professionals.
Staying Active While Staying Home: The Use of Physical Activity Technologies During Life Disruptions
Authors: Newbold Joseph W. , Rudnicka Anna , Cox Anna
Published: October 2021

One impact of the Covid-19 lockdowns was a restriction on people's ability to engage in physical activity in previously routine ways. This paper presents a two-stage mixed-method study exploring how people used technology to stay physically active during this period. We found that activity trackers reminded people to be active, while virtual coaching (i.e., video tutorials and online classes) helped them stay connected. The lockdown increased people's awareness of their activity levels and removed barriers to exercise, for example by giving them greater control over their time. However, it also created new challenges, with lack of time and space, injuries due to sudden changes in activity, and anxiety around lockdown, putting limits on physical activity. We highlight future directions that must be addressed to maximise the benefits of physical activity technologies for people trying to stay active during major life disruptions.
Association of Predicted Lean Body Mass and Fat Mass With Incident Diabetic Nephropathy in Participants With Type 2 Diabetes Mellitus: A Post Hoc Analysis of ACCORD Trial
Authors: Hukportie Daniel Nyarko , Li Fu-Rong , Zhou Rui , Zou Meng-Chen , Wu Xiao-Xiang , Wu Xian-Bo
Published: October 2021

Background

Lean body mass (LBM) and fat mass (FM) have been shown to have different associations with several chronic diseases but little is known about the sex-specific association of LBM and FM with diabetic nephropathy (DN) risk among participants with diabetes.

Methods

Participants from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study was used in a post hoc analysis to examine the association of predicted LBM index (LBMI) and FM index (FMI) with incident DN risk (defined as a composite outcome of three types of predefined DN). Because of sex differences in body composition, analyses were conducted separately using sex-specific quartiles of predicted LBMI and FMI.

Results

Of the 9,022 participants with type 2 diabetes (5,575 men and 3,447 women) included in this study, 5,374 individuals developed DN (3,396 in men and 1,978 in women). Higher quartiles of LBMI were associated with a reduced risk of DN while higher quartiles of FMI were associated with an increased higher risk of DN among men but not women. Compared with the lowest quartile, the fully adjusted hazard ratios (HRs) and 95% confidence intervals (CIs)for the highest quartile of predicted LBMI and FMI were respectively 0.83 (95% CI 1.71 – 0.96) and 1.23 (95% CI 1.06-1.43) among men; and 0.92 (95% CI 0.63 – 1.33) and 1.14 (95% CI 0.79 – 1.63) among women.

Conclusions

Among participants with diabetes, predicted LBMI was inversely associated with risk of DN while predicted FMI was positively associated with an increased risk of incident DN among men but not women. Trial registration: ClinicalTrials.gov., no. NCT00000620.
The Role of Oxytocin and the Effect of Stress During Childbirth: Neurobiological Basics and Implications for Mother and Child
Authors: Walter Michael H. , Abele Harald , Plappert Claudia F.
Published: October 2021

The neuropeptide oxytocin acts as a hormone and a neuromodulator, influencing a multitude of human social behaviors, including reproduction. During childbirth and the postpartum period, it plays a key role in regulating and controlling processes that ensure a safe birth and the health of mother and child. Especially the onset of labor, the progress of labor and initial breastfeeding are mediated by oxytocin. In the maternal brain it controls the initiation of the mother–infant bond and the mother’s emotional responses towards her child. In this review we summarize the current state of knowledge about the role of oxytocin during the different aspects and mechanisms of human childbirth, combining research from human and animal studies. Physiological and psychological stress during childbirth and lactation can have negative effects on the progress of labor, breastfeeding and bonding. We discuss how maternity caregivers can support the positive effects of oxytocin and minimize the effects of stress. Furthermore, we highlight aspects of the basic neurobiological principles and connections where further research is needed to improve our understanding of the regulation and the effects of oxytocin to support maternal and infant health.
Highly Purified Alloantigen-Specific Tregs From Healthy and Chronic Kidney Disease Patients Can Be Long-Term Expanded, Maintaining a Suppressive Phenotype and Function in the Presence of Inflammatory Cytokines
Authors: Cortés-Hernández Arimelek , Alvarez-Salazar Evelyn Katy , Arteaga-Cruz Saúl , Rosas-Cortina Katya , Linares Nadyeli , Alberú Gómez Josefina M. , Soldevila Gloria
Published: October 2021

The adoptive transfer of alloantigen-specific regulatory T cells (alloTregs) has been proposed as a therapeutic alternative in kidney transplant recipients to the use of lifelong immunosuppressive drugs that cause serious side effects. However, the clinical application of alloTregs has been limited due to their low frequency in peripheral blood and the scarce development of efficient protocols to ensure their purity, expansion, and stability. Here, we describe a new experimental protocol that allows the long-term expansion of highly purified allospecific natural Tregs (nTregs) from both healthy controls and chronic kidney disease (CKD) patients, which maintain their phenotype and suppressive function under inflammatory conditions. Firstly, we co-cultured CellTrace Violet (CTV)-labeled Tregs from CKD patients or healthy individuals with allogeneic monocyte-derived dendritic cells in the presence of interleukin 2 (IL-2) and retinoic acid. Then, proliferating CD4+CD25hiCTV− Tregs (allospecific) were sorted by fluorescence-activated cell sorting (FACS) and polyclonally expanded with anti-CD3/CD28-coated beads in the presence of transforming growth factor beta (TGF-β), IL-2, and rapamycin. After 4 weeks, alloTregs were expanded up to 2,300 times the initial numbers with a purity of >95% (CD4+CD25hiFOXP3+). The resulting allospecific Tregs showed high expressions of CTLA-4, LAG-3, and CD39, indicative of a highly suppressive phenotype. Accordingly, expanded alloTregs efficiently suppressed T-cell proliferation in an antigen-specific manner, even in the presence of inflammatory cytokines (IFN-γ, IL-4, IL-6, or TNF-α). Unexpectedly, the long-term expansion resulted in an increased methylation of the specific demethylated region of Foxp3. Interestingly, alloTregs from both normal individuals and CKD patients maintained their immunosuppressive phenotype and function after being expanded for two additional weeks under an inflammatory microenvironment. Finally, phenotypic and functional evaluation of cryopreserved alloTregs demonstrated the feasibility of long-term storage and supports the potential use of this cellular product for personalized Treg therapy in transplanted patients.
RASAL3 Is a Putative RasGAP Modulating Inflammatory Response by Neutrophils
Authors: Saito Suguru , Cao Duo-Yao , Victor Aaron R. , Peng Zhenzi , Wu Hui-Ya , Okwan-Duodu Derick
Published: October 2021

As first responder cells in host defense, neutrophils must be carefully regulated to prevent collateral tissue injury. However, the intracellular events that titrate the neutrophil’s response to inflammatory stimuli remain poorly understood. As a molecular switch, Ras activity is tightly regulated by Ras GTPase activating proteins (RasGAP) to maintain cellular active-inactive states. Here, we show that RASAL3, a RasGAP, is highly expressed in neutrophils and that its expression is upregulated by exogenous stimuli in neutrophils. RASAL3 deficiency triggers augmented neutrophil responses and enhanced immune activation in acute inflammatory conditions. Consequently, mice lacking RASAL3 (RASAL3-KO) demonstrate accelerated mortality in a septic shock model via induction of severe organ damage and hyperinflammatory response. The excessive neutrophilic hyperinflammation and increased mortality were recapitulated in a mouse model of sickle cell disease, which we found to have low neutrophil RASAL3 expression upon LPS activation. Thus, RASAL3 functions as a RasGAP that negatively regulates the cellular activity of neutrophils to modulate the inflammatory response. These results demonstrate that RASAL3 could serve as a therapeutic target to regulate excessive inflammation in sepsis and many inflammatory disease states.
Diagnostic and Prognostic Potential of Circulating and Tissue BATF2 in Nasopharyngeal Carcinoma
Authors: Cui Zhaolei , Lin Yingying , Hu Dan , Wu Jing , Peng Wei , Chen Yan
Published: October 2021

Background: Current biomarkers for nasopharyngeal carcinoma (NPC) are less effective for early diagnosis and prognosis. The basic leucine zipper ATF-like transcription factor 2 (BATF2) gene has been shown to have a tight association with the pathogenesis of various malignancies but received scant attention in NPC research. We aimed to assess the performances of circulating and tissue BATF2 in the diagnosis and prognosis of NPC.

Materials and Methods: Immunohistochemistry (IHC) microarrays were performed to quantitate the BATF2 protein expression in NPC tissues. The relationships of BATF2 protein expression with clinicopathological characteristics and NPC prognosis were assessed. BATF2 mRNA expressions in serum and serum-derived exosomes were determined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay.

Results: The IHC microarrays revealed a predominant nuclear expression of BATF2 in NPC cells. The Kaplan-Meier survival analysis showed that BATF2-positive NPC patients enjoyed longer overall survival than BATF2-negative patients. NPC patients with serum and exosomal BATF2 mRNA expressions made up 51.47 and 48.52% of all patients, respectively. The AUCs of serum and exosomal BATF2 mRNA expressions in discriminating NPC from healthy controls were 0.9409 and 0.8983. Patients who had received radiochemotherapy exhibited higher serum and exosomal BATF2 mRNA expressions versus the levels at baseline as well as those detected in recurrent patients.

Conclusion: BATF2 is expressed cancerous tissues, serum, and serum-derived exosomes in NPC patients. Circulating and tissue BATF2 can serve as a multipurpose biomarker capable of the diagnosis, prognosis prediction, efficacy evaluation, and recurrence monitoring in NPC.
Blood Pressure and T-Tau in Spinal Fluid Are Associated With Delayed Recall in Participants With Memory Complaints and Dementia of the Alzheimer’s Type
Authors: Hestad Knut Asbjorn , Horndalsveen Peter Otto , Engedal Knut
Published: October 2021

Objective: The aim of the study was to determine if systolic blood pressure (SBP), total-tau (t-tau), and beta-amyloid (Aβ) in the cerebral spinal fluid (CSF) were associated with the results on the Consortium to Establish a Registry for Alzheimer’s Disease Word List (CERAD-WL) immediate and delayed recall, and the Mini Mental State Examination (MMSE) in “younger” older adults, controlling for age and sex.

Method: We included 72 participants, mean age: 62.9 (SD 8.6, range 41–76) from a Norwegian memory clinic; eight were diagnosed with subjective cognitive decline, 32 with mild cognitive impairment (MCI), 30 with dementia of the Alzheimer’s type (DAT), and two with combined DAT and vascular dementia (VaD). Data were examined in three fitted multiple linear regression models using the CERAD-WL immediate and delayed recall, and MMSE as dependent variables; and SBP, t-tau, and Aβ as independent variables, controlling for age and sex.

Results: The strongest associations were found in the model using CERAD-WL delayed recall as the dependent variable, where 45% of the variance was explained (standardized Beta = −0.313, p = 0.004 for t-tau and standardized Beta −0.238, p = 0.01 for SBP). The unique contribution of age was close to 8%, t-tau close to 7%, and SBP above 5%. When cardiovascular medication was entered into the analysis, the explained variance increased to 51% and Aβ became significant (standardized Beta = 0.216, p = 0.03). Participants on this medication exhibited worse performance on CERAD-WL delayed recall than those who were not on medication. Age (7%), t-tau (6%), and SBP (5%) showed the same unique contribution, whereas medication contributed 6% and Aβ contributed 4%. CERAD-WL immediate recall, and MMSE yielded similar findings, but explained variance was poorer for these two variables.

Conclusions: Both elevated SBP and t-tau were associated with poorer cognitive performance, especially delayed recall. Those on cardiovascular medication were more impaired than were participants who were not on this medication—a finding that probably reflected cerebral incidents in the medicated group.
proNGF Measurement in Cerebrospinal Fluid Samples of a Large Cohort of Living Patients With Alzheimer's Disease by a New Automated Immunoassay
Authors: Malerba Francesca , Arisi Ivan , Florio Rita , Zecca Chiara , Dell'Abate Maria Teresa , Bruni Ercole Bruno , Camerini Serena , Casella Marialuisa , Logroscino Giancarlo , Cattaneo Antonino
Published: October 2021

The discovery of new biomarkers for Alzheimer's disease (AD) is essential for an accurate diagnosis, to conceive new strategies of treatments, and for monitoring the efficacy of potential disease-modifying therapies in clinical trials. proNGF levels in the cerebrospinal fluid (CSF) represent a promising diagnostic biomarker for AD, but its validation was hampered by the absence of a reliable immunoassay. In the literature, proNGF is currently measured in postmortem brain tissue by semiquantitative immunoblot. Here we describe the development and validation of a new method to measure proNGF in the CSF of living patients. This method, based on molecular size separation by capillary electrophoresis, is automated and shows a 40-fold increase in sensitivity with respect to the proNGF immunoblot, largely used in literature, and is robust, specific, and scalable to high-throughput. We have measured proNGF in the cerebrospinal fluid of 84 living patients with AD, 13 controls, and 15 subjective memory complaints (SMC) subjects. By comparing the proNGF levels in the three groups, we found a very significant difference between proNGF levels in AD samples compared with both controls and SMC subjects, while no significant difference was found between SMC and controls. Because of the development of this new immunoassay, we are ready to explore the potentiality of proNGF as a new biomarker for AD or subgroups thereof, as well as for other neurodegenerative diseases.
Human Brain and Blood N-Glycome Profiling in Alzheimer’s Disease and Alzheimer’s Disease-Related Dementias
Authors: Yu Lei , Huo Zhiguang , Yang Jingyun , Palma-Gudiel Helena , Boyle Patricia A. , Schneider Julie A. , Bennett David A. , Zhao Jinying
Published: October 2021

Glycosylation, the process of adding glycans (i.e., sugars) to proteins, is the most abundant post-translational modification. N-glycosylation is the most common form of glycosylation, and the N-glycan moieties play key roles in regulating protein functions and many other biological processes. Thus, identification and quantification of N-glycome (complete repertoire of all N-glycans in a sample) may provide new sources of biomarkers and shed light on health and disease. To date, little is known about the role of altered N-glycome in Alzheimer’s Disease and Alzheimer’s Disease-related Dementias (AD/ADRD). The current study included 45 older adults who had no cognitive impairment (NCI) at baseline, followed and examined annually, and underwent brain autopsy after death. During about 12-year follow-up, 15 developed mild cognitive impairment (MCI), 15 developed AD, and 15 remained NCI. Relative abundances of N-glycans in serum at 2 time points (baseline and proximate to death, ∼12.3 years apart) and postmortem brain tissue (dorsolateral prefrontal cortex) were quantified using MALDI-TOF-MS. Regression models were used to test the associations of N-glycans with AD/ADRD phenotypes. We detected 71 serum and 141 brain N-glycans, of which 46 were in common. Most serum N-glycans had mean fold changes less than one between baseline and proximate to death. The cross-tissue N-glycan correlations were weak. Baseline serum N-glycans were more strongly associated with AD/ADRD compared to change in serum N-glycans over time and brain N-glycans. The N-glycan associations were observed in both AD and non-AD neuropathologies. To our knowledge, this is the first comprehensive glycomic analysis in both blood and brain in relation to AD pathology. Our results suggest that altered N-glycans may serve as mechanistic biomarkers for early diagnosis and progression of AD/ADRD.
Optimal Cerebral Perfusion Pressure Guided by Brain Oxygen Pressure Measurement
Authors: Kovacs Matyas , Peluso Lorenzo , Njimi Hassane , De Witte Olivier , Gouvêa Bogossian Elisa , Quispe Cornejo Armin , Creteur Jacques , Schuind Sophie , Taccone Fabio Silvio
Published: October 2021

Background: Although increasing cerebral perfusion pressure (CPP) is commonly accepted to improve brain tissue oxygen pressure (PbtO2), it remains unclear whether recommended CPP targets (i. e., >60 mmHg) would result in adequate brain oxygenation in brain injured patients. The aim of this study was to identify the target of CPP associated with normal brain oxygenation.

Methods: Prospectively collected data including patients suffering from acute brain injury and monitored with PbtO2, in whom daily CPP challenge using vasopressors was performed. Initial CPP target was >60 mmHg; norepinephrine infusion was modified to have an increase in CPP of at least 10 mmHg at two different steps above the baseline values. Whenever possible, the same CPP challenge was performed for the following days, for a maximum of 5 days. CPP “responders” were patients with a relative increase in PbtO2 from baseline values > 20%.

Results: A total of 53 patients were included. On the first day of assessment, CPP was progressively increased from 73 (70–76) to 83 (80–86), and 92 (90–96) mmHg, which resulted into a significant PbtO2 increase [from 20 (17–23) mmHg to 22 (20–24) mmHg and 24 (22–26) mmHg, respectively; p < 0.001]. Median CPP value corresponding to PbtO2 values > 20 mmHg was 79 (74–87) mmHg, with 2 (4%) patients who never achieved such target. Similar results of CPP targets were observed the following days. A total of 25 (47%) were PbtO2 responders during the CPP challenge on day 1, in particular if low PbtO2 was observed at baseline.

Conclusions: PbtO2 monitoring can be an effective way to individualize CPP values to avoid tissue hypoxia. Low PbtO2 values at baseline can identify the responders to the CPP challenge.
Case Report: Amphiphysin Antibody-Associated Stiff-Limb Syndrome and Myelopathy: An Unusual Presentation of Breast Cancer in an Elderly Woman
Authors: Gogia Bhanu , Shanina Elena , Fang Xiang , He Jing , Li Xiangping
Published: October 2021

Background: Paraneoplastic stiff-limb syndrome (SLS) is a rare manifestation of underlying malignancy and could have distinctive features different from the classic stiff-person syndrome (SPS).

Case Description: We present a case of anti-amphiphysin antibody (Ab)-associated paraneoplastic SLS, in an 83-year-old woman with invasive ductal carcinoma of the breast. She presented with stiffness, painful spasms of the distal legs, and asymmetrical fixed posturing of the foot. There are coexisting long-tract disturbance and lower-extremity weakness. Treatment with diazepam provided symptomatic relief while plasma exchange (PLEX) did not lead to significant clinical improvement. The patient was bedridden within 3 months and passed away within 6 months from symptom onset.

Conclusion: This case highlights the importance of recognition of uncommon presentation of SPS and its oncological significance. This entity requires a high degree of suspicion for initiation of the proper workup. The rapid identification and treatment of the underlying tumor might offer the best chance for recovery.
Hepatic Resection Versus Transarterial Chemoembolization for Intermediate-Stage Hepatocellular Carcinoma: A Cohort Study
Authors: Lu Linbin , Zheng Peichan , Wu Zhixian , Chen Xiong
Published: October 2021

Background

The selection criteria for hepatic resection (HR) in intermediate-stage (IM) hepatocellular carcinoma (HCC) are still controversial. We used real-world data to evaluate the overall survival (OS) in treatment with HR or transarterial chemoembolization (TACE).

Methods

In total, 942 patients with IM-HCC were categorized into the HR group and the TACE group. OS was analyzed using the Kaplan–Meier method, log-rank test, Cox proportional hazards models, and propensity score-matched (PSM) analysis. Curve smoothing was performed through the generalized additive model. The interaction test was performed to evaluate the impact of HR on OS concerning risk factors. Also, we used multiple imputation to deal with missing data.

Results

In total, 23.0% (n = 225) of patients received HR. At a median OS of 23.7 months, HR was associated with improved OS in the multivariate analysis [hazard ratio (HzR) = 0.45, 95%CI = 0.35–0.58; after PSM: HzR = 0.56, 95%CI = 0.41–0.77]. Landmark analyses limited to long-term survivors of ≥6 months, ≥1 year, and ≥2 years demonstrated better OS with HR in all subsets (all p < 0.05). After PSM analysis, however, HR increased the risk of death by 20% (HzR = 1.20, 95%CI = 0.67–2.15) in the subgroup of patients with lactate dehydrogenase (LDH) ≤192 U/L (p for interaction = 0.037). Furthermore, the significant interaction was robust between the LDH and HR with respect to the 1-, 3-, and 5-year observed survival rates (all p < 0.05).

Conclusion

HR was superior to TACE for intermediate-stage HCC in patients with LDH levels >192 U/L. Moreover, TACE might be suitable for patients with LDH levels ≤192 U/L.
Superselective Transarterial Chemoembolization for Unresectable or “Ablation Unsuitable” Hepatocellular Carcinoma in the Caudate Lobe: A Real World, Single-Center Retrospective Study
Authors: Yan Liangliang , Ren Yanqiao , Qian Kun , Kan Xuefeng , Zhang Hongsen , Chen Lei , Liang Bin , Zheng Chuansheng
Published: October 2021

Objectives

To analyze the clinical outcomes of Transarterial chemoembolization (TACE) for unresectable or “ablation unsuitable” hepatocellular carcinoma (HCC) in the caudate lobe (CL) found at initial presentation in clinical practice.

Methods

Fifty-eight patients with HCC-CL undergoing conventional TACE from January 2015 to January 2020 were enrolled in our medical center. Overall survival (OS), progression-free survival (PFS), tumor response rate and major complication rates were analyzed. Multivariate analyses for potential clinical and radiologic factors were performed by using the Cox proportional hazard model.

Results

The median OS was 23 months (95%CI: 18.1-27.9), and the median PFS was 11 months (95%CI: 7.4-14.6). The 1-, 3-, and 5-years OS rates were 66.5%, 31.9% and 15.7%, respectively. The 0.5, 1-, and 3-years PFS rates were 60.3%, 44.5% and 6.3%, respectively. Objective response rate was 53.4% and disease control rate was 79.3%. The most serious complication was bile duct injury, with an incidence of 3.4%. Multivariable analysis revealed that total bilirubin, Barcelona Clinic Liver Cancer stage, nonselective chemoembolization and TACE session were four significant factors associated with OS.

Conclusions

Superselective TACE treatment might be associated with better survival benefits in unresectable or “ablation unsuitable” HCC in the CL without macroscopic vascular invasion (MVI) and adequate liver function, compared with the non-selective TACE group, and should be considered as an important reliable therapy for surgeons and interventional radiologists.
Targeted Near-Infrared Fluorescence Imaging With Iodized Indocyanine Green in Preoperative Pulmonary Localization: Comparative Efficacy, Safety, Patient Perception With Hook-Wire Localization
Authors: Ding Ning , Wang Kefei , Cao Jian , Hu Ge , Wang Zhiwei , Jin Zhengyu
Published: October 2021

Background

Precise preoperative localization is of great importance to improve the success rate and reduce the operation time of VATS surgery. This study aimed to assess the efficacy, safety, patient perception between CT-guided indocyanine green (ICG) preoperative localization of lung nodule and hook-wire localization.

Methods

65 patients with 85 clinically suspicious pulmonary nodules underwent ICG preoperative localization in this study, and 92 patients with 95 nodules localized by conventional hook-wire served as controls. Both hook-wire localization and ICG injection were performed under CT guidance. Successful targeting rate, success rate in the operative field, incidence rate of complications and respiratory pain score were recorded and compared.

Results

The successful targeting rate for both groups is 100%, however, due to hook-wire dislodgement, the success rate in the VATS operation field of the hook-wire group (95.6%) is lower than that of the ICG group (100%), with no significant difference(p=0.056). The overall complication rate of the hook-wire group (37.0%) is significantly higher than the ICG group (35.4%) (p=0.038). The mean respiratory pain score of the hook-wire group is 3.70 ± 1.25, which is significantly higher than that of the ICG group (2.85 ± 1.05) (p<0.001).

Conclusions

ICG composed with contrast mixture are superior to the conventional hook-wire preoperative lung nodule localization procedure, with a lower complication rate, lower pain score, and relatively higher success rate. ICG is a promising alternative method for pulmonary nodule preoperative localization.
Molecular Mechanisms of Ferroptosis and Its Roles in Hematologic Malignancies
Authors: Zhao Yan , Huang Zineng , Peng Hongling
Published: October 2021

Cell death is essential for the normal metabolism of human organisms. Ferroptosis is a unique regulated cell death (RCD) mode characterized by excess accumulation of iron-dependent lipid peroxide and reactive oxygen species (ROS) compared with other well-known programmed cell death modes. It has been currently recognized that ferroptosis plays a rather important role in the occurrence, development, and treatment of traumatic brain injury, stroke, acute kidney injury, liver damage, ischemia–reperfusion injury, tumor, etc. Of note, ferroptosis may be explained by the expression of various molecules and signaling components, among which iron, lipid, and amino acid metabolism are the key regulatory mechanisms of ferroptosis. Meanwhile, tumor cells of hematological malignancies, such as leukemia, lymphoma, and multiple myeloma (MM), are identified to be sensitive to ferroptosis. Targeting potential regulatory factors in the ferroptosis pathway may promote or inhibit the disease progression of these malignancies. In this review, a systematic summary was conducted on the key molecular mechanisms of ferroptosis and the current potential relationships of ferroptosis with leukemia, lymphoma, and MM. It is expected to provide novel potential therapeutic approaches and targets for hematological malignancies.
Modification of EBV-Associated Pathologies and Immune Control by Coinfections
Authors: Münz Christian
Published: October 2021

The oncogenic Epstein–Barr virus (EBV) persistently infects more than 95% of the human adult population. Even so it can readily transform human B cells after infection in vitro, it only rarely causes tumors in patients. A substantial proportion of the 1% of all human cancers that are associated with EBV occurs during coinfections, including those with the malaria parasite Plasmodium falciparum, the human immunodeficiency virus (HIV), and the also oncogenic and closely EBV-related Kaposi sarcoma-associated herpesvirus (KSHV). In this review, I will discuss how these infections interact with EBV, modify its immune control, and shape its tumorigenesis. The underlying mechanisms reveal new aspects of EBV-associated pathologies and point toward treatment possibilities for their prevention by the human immune system.
Analysis of a Cooperation and Interventional Model in Humanitarian Medicine
Authors: Marianeschi Stefano M. , Uricchio Nicola , Cerri Gianandrea Bern , Ghiselli Simone , Carro Cristina , Albano Giulia , Viola Nicola
Published: October 2021

Background: Every year, around 15 million children, in developing countries, die or develop life-long disabilities because of congenital cardiac diseases. In this report we measure the effect of a pediatric cardiac surgery humanitarian project on the health of the individual and on the potential influence this has on the countries economy and its growing health services.

Methods: We collected and analyzed data from the Italian NGO, Mission Bambini's database, including all congenital cardiac missions undertaken in Cambodia between 2012 and 2019. DALY's (Disability Adjusted Life Years) saved by the humanitarian mission were estimated and used to reflect on the impact this had on the populations economy. Progression in the local medical teams skills emulated the advancements made in the health sector of the region.

Results: Between 2012 and 2019, 128 patients underwent a congenital cardiac operation at Angkor Hospital for Children at Siem Reap, Cambodia. The median age was 6 years. The majority of the pathologies included VSD, TOF, ASD. The mean Aristotle's Complexity Score was 6. Post-operative mortality was 0.8% (1/128). The cost-effectiveness analysis identified 5.360 DALY's saved by surgery. The competency of the local team was progressive with them being able to handle more complex cases on subsequent missions.

Conclusion: In developing Countries, performing congenital cardiac surgery cases can be carried out successfully with improvement in both the economy and the health system of the country by increasing the years and the quality of life of the working population and developing the expertise of the regional team.
Single-Target Versus Multi-Target Drugs Versus Combinations of Drugs With Multiple Targets: Preclinical and Clinical Evidence for the Treatment or Prevention of Epilepsy
Authors: Löscher Wolfgang
Published: October 2021

Rationally designed multi-target drugs (also termed multimodal drugs, network therapeutics, or designed multiple ligands) have emerged as an attractive drug discovery paradigm in the last 10–20 years, as potential therapeutic solutions for diseases of complex etiology and diseases with significant drug-resistance problems. Such agents that modulate multiple targets simultaneously are developed with the aim of enhancing efficacy or improving safety relative to drugs that address only a single target or to combinations of single-target drugs. Although this strategy has been proposed for epilepsy therapy >25 years ago, to my knowledge, only one antiseizure medication (ASM), padsevonil, has been intentionally developed as a single molecular entity that could target two different mechanisms. This novel drug exhibited promising effects in numerous preclinical models of difficult-to-treat seizures. However, in a recent randomized placebo-controlled phase IIb add-on trial in treatment-resistant focal epilepsy patients, padsevonil did not separate from placebo in its primary endpoints. At about the same time, a novel ASM, cenobamate, exhibited efficacy in several randomized controlled trials in such patients that far surpassed the efficacy of any other of the newer ASMs. Yet, cenobamate was discovered purely by phenotype-based screening and its presumed dual mechanism of action was only described recently. In this review, I will survey the efficacy of single-target vs. multi-target drugs vs. combinations of drugs with multiple targets in the treatment and prevention of epilepsy. Most clinically approved ASMs already act at multiple targets, but it will be important to identify and validate new target combinations that are more effective in drug-resistant epilepsy and eventually may prevent the development or progression of epilepsy.
Large Amino Acid Mimicking Selenium-Doped Carbon Quantum Dots for Multi-Target Therapy of Alzheimer’s Disease
Authors: Zhou Xi , Hu Shuyang , Wang Shuangling , Pang Yu , Lin Yulong , Li Meng
Published: October 2021

Multi-target intervention and synergistic treatment are critical for the drug development of Alzheimer’s disease (AD) due to its complex and multifactional nature. Oxidative stress and amyloid β peptides (Aβ) accumulation have been recognized as therapeutic targets for AD. Herein, with ability to inhibit Aβ aggregation and the broad-spectrum antioxidant properties, the large amino acid mimicking selenium-doped carbon quantum dots (SeCQDs) are presented as novel nanoagents for multi-target therapy of AD. Compared with the precursor, selenocystine, SeCQDs which maintain the intrinsic properties of both selenium and carbon quantum dots (CQDs) possess good biocompatibility and a remarkable ROS-scavenging activity. Moreover, the functionalized α-carboxyl and amino groups on edge of SeCQDs can trigger multivalent interactions with Aβ, leading to the ability of SeCQDs to inhibit Aβ aggregation. In vivo study demonstrated that SeCQDs can significantly ameliorate the Aβ induced memory deficits, reduce Aβ accumulation and inhibit neuron degeneration in AD model rats. The versatility of functionalization and potential ability to cross the blood-brain barrier (BBB) make SeCQDs as prospective nanodrugs for treating AD.
The Circadian Oscillator of the Cerebellum: Triiodothyronine Regulates Clock Gene Expression in Granule Cells in vitro and in the Cerebellum of Neonatal Rats in vivo
Authors: Bering Tenna , Hertz Henrik , Rath Martin Fredensborg
Published: October 2021

The central circadian clock resides in the suprachiasmatic nucleus (SCN) of the hypothalamus, but an SCN-dependent molecular circadian oscillator is present in the cerebellar cortex. Recent findings suggest that circadian release of corticosterone is capable of driving the circadian oscillator of the rat cerebellum. To determine if additional neuroendocrine signals act to shape cerebellar clock gene expression, we here tested the role of the thyroid hormone triiodothyronine (T3) in regulation of the cerebellar circadian oscillator. In cultured cerebellar granule cells from mixed-gender neonatal rats, T3 treatment affected transcript levels of the clock genes Per2, Arntl, Nr1d1, and Dbp, suggesting that T3 acts directly on granule cells to control the circadian oscillator. We then used two different in vivo protocols to test the role of T3 in adult female rats: Firstly, a single injection of T3 did not influence clock gene expression in the cerebellum. Secondly, we established a surgical rat model combining SCN lesion with a programmable micropump infusing circadian physiological levels of T3; however, rhythmic infusion of T3 did not reestablish differential clock gene expression between day and night in SCN lesioned rats. To test if the effects of T3 observed in vitro were related to the developmental stage, acute injections of T3 were performed in mixed-gender neonatal rats in vivo; this procedure significantly affected cerebellar expression of the clock genes Per1, Per2, Nr1d1, and Dbp. Developmental comparisons showed rhythmic expression of all clock genes analyzed in the cerebellum of adult rats only, whereas T3 responsiveness was limited to neonatal animals. Thus, T3 shapes cerebellar clock gene profiles in early postnatal stages, but it does not represent a systemic circadian regulatory mechanism linking the SCN to the cerebellum throughout life.
Creole Prosodic Systems Are Areal, Not Simple
Authors: Yakpo Kofi
Published: October 2021

This study refutes the common idea that tone gets simplified or eliminated in creoles and contact languages. Speakers of African tone languages imposed tone systems on all Afro-European creoles spoken in the tone-dominant linguistic ecologies of Africa and the colonial Americas. African speakers of tone languages also imposed tone systems on the colonial varieties of English, French, Spanish, and Portuguese spoken in tonal Africa. A crucial mechanism involved in the emergence of the tone systems of creoles and colonial varieties is stress-to-tone mapping. A typological comparison with African non-creole languages shows that creole tone systems are no simpler than African non-creole tone systems. Demographic, linguistic, and social changes in an ecology can lead to switches from tone to stress systems and vice versa. As a result, there is an areal continuum of tone systems roughly coterminous with the presence of tone in the east (Africa) and stress in the west (Americas). Transitional systems combining features of tone and stress converge on the areal buffer zone of the Caribbean. The prosodic systems of creoles and European colonial varieties undergo regular processes of contact, typological change and areal convergence. None of these are specific to creoles. So far, creoles and colonial varieties have not featured in work on the world-wide areal clustering of prosodic systems. This study therefore aims to contribute to a broader perspective on prosodic contact beyond the narrow confines of the creole simplicity debate.
Body Mobility and Attention Networks in 6- to 7-Year-Old Children
Authors: Rosenbaum Joëlle , Hascoët Jean-Michel , Hamon Isabelle , Petel Arthur , Caudron Sébastien , Ceyte Hadrien
Published: October 2021

Learning in 6- to 7-year-old children is strongly influenced by three functions of attention: alertness, orienting, and executive control. These functions share a close relationship with body mobility, such as the posture adopted or a request to stay still during tasks. The aim of this study (ClinicalTrials.gov) was to analyze the influence of body posture (standing versus sitting) and the influence of these imposed postures compared to a free body mobility on attention functions in 6- to 7-year-old children. Twenty-one children (11 girls) with a mean age of 6.7±0.6years performed the Attention Network Test for Children in three-body mobility conditions: sitting still, standing still, and free to move. Three attentional scores were calculated which would separately reflect performance of alertness, orienting, and executive control. Overall, no difference in alertness performance was found between the three bodily mobility conditions. In addition, our results suggest a general poor orienting performance in children, whatever the body mobility condition, which might be related to their young age. Finally, children improved their executive control performance when they stood still, probably due to an improvement in arousal and mental state.
Impact of Behavioral and Psychological Symptoms on Caregiver Burden in Patients With Dementia With Lewy Bodies
Authors: Kanemoto Hideki , Sato Shunsuke , Satake Yuto , Koizumi Fuyuki , Taomoto Daiki , Kanda Atsushi , Wada Tamiki , Yoshiyama Kenji , Ikeda Manabu
Published: October 2021

Background/Objective: Behavioral and psychological symptoms of dementia (BPSD) have been reported to affect caregiver burden in patients with dementia with Lewy bodies (DLB). However, the factor structure of BPSD and the factors that affect caregiver burden in DLB remain unknown. This study sought to classify BPSD and to reveal what type of BPSD affects caregiver burden in patients with DLB.

Methods: We collected data on neuropsychiatric inventory-plus (NPI-plus), Zarit Burden Interview (ZBI), Mini-Mental State Examination (MMSE), Lawton's Instrumental Activities of Daily Living and Physical Self-Maintenance Scale (IADL/PSMS), age, and sex of 102 patients with probable DLB. An exploratory factor analysis of 13 items of the NPI-plus was carried out to classify BPSD. Multivariate regression analyses were conducted to extract the clinical variables related to caregiver burden, including factors resulting from the aforementioned factor analysis.

Results: The mean age and MMSE score were 78.6 (5.6) and 20.2 (5.2), respectively. Factor analysis revealed four factors of “psychosis,” “affection,” “wakefulness,” and “hyperactivity.” “Psychosis” and “affection” factors as well as MMSE, IADL, and PSMS were significantly associated with ZBI. Multivariate regression analyses revealed that the total score of ZBI was associated with “psychosis,” “affection,” and IADL, that the personal strain score of ZBI was associated with “affection” and IADL, and that the role strain score of ZBI was associated with “wakefulness” and IADL.

Conclusions: BPSD in DLB consists of three factors common to Alzheimer's disease and a specific “wakefulness” factor. In addition to IADL, each BPSD factor would affect caregiver burden in different ways in DLB.
German Law Reform Does Not Reduce the Prevalence of Coercive Measures in Residential Institutions for Children, Adolescents, and Young Adults With Intellectual and Developmental Disabilities
Authors: Geissler Julia M. , Werner Elisabeth , Dworschak Wolfgang , Romanos Marcel , Ratz Christoph
Published: October 2021

Background: Approximately 10% of children, adolescents and young adults with an intellectual and developmental disability (IDD) in Bavaria live in residential institutions. 2015 saw media reports raising suspicions about excessive use of coercive measures (cM) in those institutions. Until a law reform at the end of 2017 made permission from family courts mandatory for cM, their use was governed by parental consent. The REDUGIA project conducted a representative survey comparing cM and their relation to challenging behaviour (cB) and employee stress in Bavaria pre and post reform.

Methods: We sent questionnaires to 65 residential institutions for children, adolescents and young adults with IDD in 2017 (pre reform, T1) and 2019 (post reform, T2). To assess changes, we analysed data from all available questionnaire pairs (T1 and T2, N = 43). We calculated paired t-test and correlative analyses concerning the relationship between cB, cM, and employee stress.

Results: The number of residents overall (T1: N = 1,661; T2: N = 1,673) and per institution (T1: m = 38.6 ± 32.0; T2: m = 38.9 ± 34.5, p = 0.920) remained stable. We did not see any changes in the Index cB (p = 0.508) or the proportion of residents per institution displaying various types of challenging behaviour (all ps>0.220). There was no change in the Index cM (p = 0.089) or any indicator of employee stress, all ps > 0.323. At follow-up, the Index cB correlated positively with the Index cM (r = 0.519 p < 0.001). Regarding employee stress, the Index cB correlated positively with the frequency of sick leave (r = 0.322, p = 0.037) and physical attacks on employees (r = 0.552, p < 0.001). The Index cM also correlated positively with the frequency of sick leave (r = 0.340, p = 0.028) and physical attacks on employees (r = 0.492, p = 0.001).

Discussion: Coercive measures are not a general phenomenon, but are focused on specialised institutions. The law reform did not lead to changes in the number of children, adolescents and young adults with IDD affected by coercive measures in residential institutions in Bavaria. There were still large discrepancies between institutions in the prevalence of challenging behaviour and coercive measures. Coercive measures were associated with challenging behaviour and employee stress. Taken together, findings from REDUGIA emphasise the need to prevent challenging behaviour and thus coercive measures.
Centering Equity in Sustainable Food Systems Education
Authors: Sterling Eleanor J. , Betley Erin , Ahmed Selena , Akabas Sharon , Clegg Daniel J. , Downs Shauna , Izumi Betty , Koch Pamela , Kross Sara M. , Spiller Karen , Teron Lemir , Valley Will
Published: October 2021

Sustainable food systems education (SFSE) is rapidly advancing to meet the need for developing future professionals who are capable of effective decision-making regarding agriculture, food, nutrition, consumption, and waste in a complex world. Equity, particularly racial equity and its intersectional links with other inequities, should play a central role in efforts to advance SFSE given the harmful social and environmental externalities of food systems and ongoing oppression and systemic inequities such as lack of food access faced by racialized and/or marginalized populations. However, few institutional and intra-disciplinary resources exist on how to engage students in discussion about equity and related topics in SFSE. We present perspectives based on our multi-institutional collaborations to develop and apply pedagogical materials that center equity while building students' skills in systems thinking, critical reflection, and affective engagement. Examples are provided of how to develop undergraduate and graduate sustainable food systems curricula that embrace complexity and recognize the affective layers, or underlying experiences of feelings and emotions, when engaging with topics of equity, justice, oppression, and privilege.