bluuebunny/crossref_metadata_2025 huggingface dataset:
Disease severity and status in Stevens–Johnson syndrome and toxic epidermal necrolysis: Key knowledge gaps and research needs
Authors: Lehloenya Rannakoe J.
Published: September 2022

Stevens–Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are on a spectrum of cutaneous drug reactions characterized by pan-epidermal necrosis with SJS affecting < 10% of body surface area (BSA), TEN > 30%, and SJS/TEN overlap between 10 and 30%. Severity-of-illness score for toxic epidermal necrolysis (SCORTEN) is a validated tool to predict mortality rates based on age, heart rate, BSA, malignancy and serum urea, bicarbonate, and glucose. Despite improved understanding, SJS/TEN mortality remains constant and therapeutic interventions are not universally accepted for a number of reasons, including rarity of SJS/TEN; inconsistent definition of cases, disease severity, and endpoints in studies; low efficacy of interventions; and variations in treatment protocols. Apart from mortality, none of the other endpoints used to evaluate interventions, including duration of hospitalization, is sufficiently standardized to be reproducible across cases and treatment centers. Some of the gaps in SJS/TEN research can be narrowed through international collaboration to harmonize research endpoints. A case is made for an urgent international collaborative effort to develop consensus on definitions of endpoints such as disease status, progression, cessation, and complete re-epithelialization in interventional studies. The deficiencies of using BSA as the sole determinant of SJS/TEN severity, excluding internal organ involvement and extension of skin necrosis beyond the epidermis, are discussed and the role these factors play on time to healing and mortality beyond the acute stage is highlighted. The potential role of artificial intelligence, biomarkers, and PET/CT scan with radiolabeled glucose as markers of disease status, activity, and therapeutic response is also discussed.
Determining why continuous cropping reduces the production of the morel Morchella sextelata
Authors: Wei-Ye Liu , Hong-Bo Guo , Ke-Xin Bi , Alekseevna Sibirina Lidiya , Xiao-Jian Qi , Xiao-Dan Yu
Published: September 2022

Artificial cultivation of Morchella sextelata and other morels is expanding in China, but continuous cropping reduces Morchella for unknown reasons. Here, we investigated soil that had been used or not used for M. sextelata cultivation for 0, 1, and 2 years. We found that the continuous cropping of M. sextelata substantially reduced the pH and the nutrient content of the hyphosphere soil and increased sclerotia formation by M. sextelata. Changes in the structure of bacterial and fungal communities were associated with levels of available nitrogen (N) and phosphorus in the soil. With continuous cropping, the richness and diversity of fungal and bacterial communities increased, but the abundance of Bacillus and Lactobacillus decreased and the abundance of pathogenic fungi increased. FAPROTAX analysis indicated that N cycle functions were enriched more with than without continuous cultivation, and that enrichment of N cycle and sulfate respiration functions was higher in the second than in the first year of cultivation. FunGuild analysis indicated that the functions related to pathotrophs and wood saprotrophs were enriched by M. sextelata cultivation. Overall, the results suggest that continuous cropping may reduce M. sextelata production by acidifying the soil and increasing the abundance of pathogenic fungi. Additional research is needed to determine whether increases in the abundance of pathogenic fungi and changes in soil chemistry result in the declines in production that occur with continuous M. sextelata cultivation.
Differences in microbial diversity and environmental factors in ploughing-treated tobacco soil
Authors: Zhang Yuzhen , Bo Guodong , Shen Minchong , Shen Guoming , Yang Jianming , Dong Shanyu , Shu Zhaohe , Wang Zhaobao
Published: September 2022

During agricultural production, plowing affects the existing traits of the planted soil, including environmental factors (physicochemical properties and soil enzymatic activity) and microbial community, but whether deep tillage and conventional tillage cause differences in soil microecology are unknown. In this study, the 16S rRNA high-throughput sequencing technology was combined with soil environmental factor detection to analyze the differences in microbial diversity of smokey soils at different depths. As a result, the composition and structure of microbial community varied in different soil depth after plowing. Two dominant phyla, Actinobacteria and Acidobacteria, have varied a lot between the deep-plowing treatment HS3 (the sample in 10–20 cm depth after deep-plowing treatment) sample and the conventional tillage HC3 (treatment the sample in 10–20 cm depth after conventional tillage) sample. The abundance of Actinobacteria has increased significantly, while the abundance of Acidobacteria has decreased significantly. Moreover, deep tillage increased the activity of sucrase (S-SC) and nitrate reductase (NR) in samples with soil depth below 20 cm. In summary, deep tillage disturbed spatial microbial diversity and environmental factors significantly. This would provide new guidance for improving farmland management strategies, optimizing the activation methods of soil layers, further improving crop planting soil, and increasing crop yield.
Delivering gene therapy for mucopolysaccharide diseases
Authors: Wood Shaun R. , Bigger Brian W.
Published: September 2022

Mucopolysaccharide diseases are a group of paediatric inherited lysosomal storage diseases that are caused by enzyme deficiencies, leading to a build-up of glycosaminoglycans (GAGs) throughout the body. Patients have severely shortened lifespans with a wide range of symptoms including inflammation, bone and joint, cardiac, respiratory and neurological disease. Current treatment approaches for MPS disorders revolve around two main strategies. Enzyme replacement therapy (ERT) is efficacious in treating somatic symptoms but its effect is limited for neurological functions. Haematopoietic stem cell transplant (HSCT) has the potential to cross the BBB through monocyte trafficking, however delivered enzyme doses limit its use almost exclusively to MPSI Hurler. Gene therapy is an emerging therapeutic strategy for the treatment of MPS disease. In this review, we will discuss the various vectors that are being utilised for gene therapy in MPS as well as some of the most recent gene-editing approaches undergoing pre-clinical and clinical development.
Urine cytological study in patients with clinicopathologically confirmed neuronal intranuclear inclusion disease
Authors: Zhou Yiyi , Huang Pengcheng , Huang Zhaojun , Peng Yun , Zheng Yilei , Yu Yaqing , Zhu Min , Deng Jianwen , Wang Zhaoxia , Hong Daojun
Published: September 2022

Objective

The diagnosis of neuronal intranuclear inclusion disease (NIID) is currently based on CGG repeat expansion in the 5′UTR of the NOTCH2NLC gene, or p62-positive intranuclear inclusions in skin biopsy. The purpose of this study is to explore the value of non-invasive pathological findings in urine sediment cells from NIID patients.

Materials and methods

Ten patients with clinically suspected NIID were enrolled for skin biopsy and gene screening. Morning urine (500 ml) was collected from each patient, and cell sediment was obtained by centrifugation. Urine cytology, including Giemsa staining, p62 immunostaining, and electron microscopic examination, were conducted on cell sediment.

Results

The main clinical symptoms of 10 patients included episodic disturbance of consciousness, cognitive impairment, tremor, limb weakness, and so on. Cerebral MRI showed that 9 patients had linear DWI high signal in the corticomedullary junction. Genetic testing found that the number of CGG repeat ranged from 96 to 158 in the NOTCH2NLC gene. Skin biopsy revealed that all patients showed p62-positive intranuclear inclusions in 18.5 ± 6.3% of the duct epithelial cells of sweat gland. In contrast, urine sediment smears revealed that only 3 patients had p62 positive intranuclear inclusions in 3.5 ± 1.2% of the sedimentary cells. Ultrastructural examinations showed that intranuclear inclusions were also identified in the cell sediment of the 3 patients.

Conclusion

Urine cytology may be a new and non-invasive pathological diagnosis technique for some NIID patients, although the positive rate is not as high as that of skin biopsy, which is a sensitive and reliable pathological method for NIID.
Differences in brain activations between micro- and macro-expressions based on electroencephalography
Authors: Zhao Xingcong , Liu Ying , Chen Tong , Wang Shiyuan , Chen Jiejia , Wang Linwei , Liu Guangyuan
Published: September 2022

Micro-expressions can reflect an individual’s subjective emotions and true mental state and are widely used in the fields of mental health, justice, law enforcement, intelligence, and security. However, the current approach based on image and expert assessment-based micro-expression recognition technology has limitations such as limited application scenarios and time consumption. Therefore, to overcome these limitations, this study is the first to explore the brain mechanisms of micro-expressions and their differences from macro-expressions from a neuroscientific perspective. This can be a foundation for micro-expression recognition based on EEG signals. We designed a real-time supervision and emotional expression suppression (SEES) experimental paradigm to synchronously collect facial expressions and electroencephalograms. Electroencephalogram signals were analyzed at the scalp and source levels to determine the temporal and spatial neural patterns of micro- and macro-expressions. We found that micro-expressions were more strongly activated in the premotor cortex, supplementary motor cortex, and middle frontal gyrus in frontal regions under positive emotions than macro-expressions. Under negative emotions, micro-expressions were more weakly activated in the somatosensory cortex and corneal gyrus regions than macro-expressions. The activation of the right temporoparietal junction (rTPJ) was stronger in micro-expressions under positive than negative emotions. The reason for this difference is that the pathways of facial control are different; the production of micro-expressions under positive emotion is dependent on the control of the face, while micro-expressions under negative emotions are more dependent on the intensity of the emotion.
ERBB2 promoter demethylation and immune cell infiltration promote a poor prognosis for cancer patients
Authors: Wang Hongting , Jiang Yongxu , Jin Huanhuan , Wang Cunqin
Published: September 2022

Background

Receptor tyrosine-protein kinase erbB-2 (ERBB2) expression is a critical factor for the prognosis of various cancers. ERBB2 enrichment indicates a poor prognosis in some cancer types but could be a favorable prognostic factor in others.

Methods

We analyzed DNA methylation, mRNA, protein, immune cell infiltration, and related signaling pathways using TIMER2.0, GEPIA2, STRING, and UALCAN portal datasets in tumor tissues of diverse cancer types and their matched normal tissues.

Results

ERBB2 promoter demethylation increases transcript protein amplification and promotes a poor prognosis for cancer patients. ERBB2 gain-of-function procures immune cell infiltration for tumor growth and drives away T regulatory cells, which suppress or downregulate induction and proliferation of effector T cells. The downstream signaling pathways, such as tumor proliferation, ECM-related genes, and degradation of ECM, are involved in ERBB2 gene demethylation and immune activation in cancer progression.

Conclusion

ERBB2 gene demethylation leads to a poor prognosis in cancer patients, which is strongly influenced by the composition and abundance of tumor immune cell infiltration. ERBB2 demethylation could be used in clinical practice to identify immune profiles and direct therapeutic strategies.
A positive feedback loop between tryptophan hydroxylase 1 and β-Catenin/ZBP-89 signaling promotes prostate cancer progression
Authors: Ge Chengguo , Yan Jiusong , Yuan Xiaoyu , Xu Guangyong
Published: September 2022

Alterations in tryptophan (Trp) metabolism facilitate the continuous modulation of tumor progression, including tumor growth, distant metastasis, and chemoresistance development. Although there is a high correlation between Trp metabolism and tumor progression, it is unknown whether and how Trp metabolism affects the development of prostate cancer. In this study, we reported that the overexpression of Trp hydroxylase 1 (TPH1) caused the upregulation of Trp hydroxylation and mediated the production of 5-hydroxytryptamine (5-HT), contributing to tumor growth and poor prognosis in patients with prostate cancer. An increase in 5-HT levels triggered the activation of the Axin 1/β-catenin signaling pathway, thus enhancing cell proliferation and migration. Consequently, β-catenin cooperated with the Krüppel-type zinc finger family transcription factor ZBP-89 to upregulate TPH1 expression, further promoting Trp hydroxylation and forming the TPH1/5-HT/β-catenin/ZBP-89/THP1 positive feedback signaling loop. Interruption of the signaling loop by the THP1 inhibitor 4-chloro-dl-phenylalanine (PCPA) significantly improved anticancer effects and suppressed lung metastasis in prostate cancer–bearing mice. Our findings revealed a mechanism by which TPH1 promotes prostate cancer growth by inducing Trp hydroxylation and identified a novel THP1 target for an innovative prostate cancer therapeutic strategy.
Urinary incontinence as a possible signal of neuromuscular toxicity during immune checkpoint inhibitor treatment: Case report and retrospective pharmacovigilance study
Authors: Hu Yizhang , Lu Wenchao , Tang Borui , Zhao Zhixia , An Zhuoling
Published: September 2022

Background

Immune checkpoint inhibitors (ICIs) are associated with different immune-related adverse events (irAEs), but there is limited evidence regarding the association between urinary incontinence and ICIs.

Methods

We described the case of a patient experiencing urinary incontinence who later experienced a series of irAEs such as myocarditis, myositis, and neurologic diseases while on ICI treatment in our hospital. In addition, we queried the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) from the third quarter of 2010 to the third quarter of 2020 to perform a retrospective study to characterize the clinical features of urinary incontinence associated with ICIs.

Result

In the FAERS study, 59 cases of ICI-related urinary incontinence were retrieved, and approximately 32.2% of the cases were fatal. Combination therapy with nervous system drugs and age >80 years old were the significant risk factors for fatal outcomes. Among these cases of ICI-related urinary incontinence, 40.7% (n = 24) occurred concomitantly with other adverse events, especially, neurological (fifteen cases), cardiovascular (seven cases), musculoskeletal (six cases), and urological disorders (five cases). Five cases had an overlapping syndrome similar to our case report, including one case of myasthenia gravis with myocarditis and another of myasthenic syndrome with polymyositis.

Conclusion

ICI-related urinary incontinence might be a signal of fatal neuromuscular irAEs, especially when it occurs concomitantly with ICI-associated neuromuscular–cardiovascular syndrome. Clinicians should be aware of the occurrence of urinary incontinence to identify potentially lethal irAEs in the early phase.
Incidence and risk factors for myocardial injury after laparoscopic adrenalectomy for pheochromocytoma: A retrospective cohort study
Authors: Lan Ling , Shu Qian , Yu Chunhua , Pei Lijian , Zhang Yuelun , Xu Li , Huang Yuguang
Published: September 2022

Background

Pheochromocytoma is a rare catecholamine-secreting tumor. Tumor resection remains a high-risk procedure due to intraoperative hemodynamic instability nowadays, which may lead to myocardial injury. We aimed to determine the incidence and associated risk factors for myocardial injury after laparoscopic adrenalectomy for pheochromocytoma.

Methods

Adult patients (n=350, American Society of Anesthesiology physical status 1–3) who underwent elective laparoscopic adrenalectomy for pheochromocytoma under general anesthesia between January 31, 2013 and January 31, 2020 were included in this observational, retrospective, single-center, cohort study. Blood troponin I levels were measured before and during the first 2 days after surgery. Myocardial injury was defined as an elevated troponin I level exceeding the 99th percentile upper reference limit due to cardiac ischemic causes.

Results

Myocardial injury occurred in 42/350 patients (12.0%, 95% confidence interval: 9.0%–15.9%). In multivariable analysis (adjusted odds ratios [95% confidence intervals]), previous ischemic heart disease or stroke (5.04 [1.40–18.08]; P=0.013), intraoperative heart rate >115 bpm (2.55 [1.06–6.12]; P=0.036), intraoperative systolic blood pressure >210 mmHg (2.38 [1.00–5.66]; P=0.049), and perioperative decrease in hemoglobin level(1.74 [1.15–2.64] per g/dL decrease; P=0.008) were associated with an increased risk of myocardial injury. For the cumulative duration of dichotomized intraoperative hemodynamics, multivariable analysis showed that intraoperative heart rate >115 bpm for >1 minute (2.67 [1.08–6.60]; P=0.034) and systolic blood pressure >210 mmHg for >1 minute (3.78 [1.47–9.73]; P=0.006) were associated with an increased risk of myocardial injury. The risk of myocardial injury progressively increased with a longer cumulative duration of intraoperative tachycardia and hypertension.

Conclusions

There is a high incidence of myocardial injury after laparoscopic adrenalectomy for pheochromocytoma. The identified risk factors may assist physicians in detecting high-risk patients and providing guidance for intraoperative hemodynamics and perioperative hemoglobin management.
Case report: Post-therapeutic laryngeal carcinoma patient possessing a high ratio of aneuploid CTECs to CTCs rapidly developed de novo malignancy in pancreas
Authors: Mi Jiaoping , Yang Fang , Liu Jiani , Liu Mingyang , Lin Alexander Y. , Wang Daisy Dandan , Lin Peter Ping , Zeng Qi
Published: September 2022

Effectively evaluating therapeutic efficacy, detecting minimal residual disease (MRD) after therapy completion, and predicting early occurrence of malignancy in cancer patients remain as unmet imperative clinical demands. This article presents a case of a laryngeal carcinoma patient who had a surgical resection and complete post-operative chemoradiotherapy in combination with the targeted therapy, then rapidly developed pancreatic adenocarcinoma. Detected by SE-iFISH, the patient had a substantial amount of 107 non-hematological aneuploid circulating rare cells including 14 circulating tumor cells (CTCs, CD31-/CD45-) and 93 circulating tumor endothelial cells (CTECs, CD31+/CD45-) with a high ratio of CTECs/CTCs > 5 upon finishing post-surgical combination regimens. Positive detection of those aneuploid non-hematological circulating rare cells was five months prior to subsequent plasma CA19-9 increasing and ten months before the de novo pancreatic cancer was diagnosed by medical imaging modalities. Besides previously reported clinical utilities of co-detection of aneuploid CD31- CTCs and CD31+ CTECs in real-time evaluation of therapeutic efficacy, longitudinal monitoring of emerging treatment resistance and adequate detection of MRD, a large cohort study is necessary to further investigate whether, and how, a high ratio of MRD CTECs to CTCs may function as an appropriate index forecasting either occurrence or metastatic distant recurrence of malignancy in post-therapeutic cancer patients.
Proteomics unite traditional toxicological assessment methods to evaluate the toxicity of iron oxide nanoparticles
Authors: Han Junyuan , Tian Yongzhang , Wang Minghan , Li Yajuan , Yin Jiye , Qu Wensheng , Yan Changhui , Ding Rigao , Guan Yongbiao , Wang Quanjun
Published: September 2022

Iron oxide nanoparticles (IONPs) are the first generation of nanomaterials approved by the Food and Drug Administration for use as imaging agents and for the treatment of iron deficiency in chronic kidney disease. However, several IONPs-based imaging agents have been withdrawn because of toxic effects and the poor understanding of the underlying mechanisms. This study aimed to evaluate IONPs toxicity and to elucidate the underlying mechanism after intravenous administration in rats. Seven-week-old rats were intravenously administered IONPs at doses of 0, 10, 30, and 90 mg/kg body weight for 14 consecutive days. Toxicity and molecular perturbations were evaluated using traditional toxicological assessment methods and proteomics approaches, respectively. The administration of 90 mg/kg IONPs induced mild toxic effects, including abnormal clinical signs, lower body weight gain, changes in serum biochemical and hematological parameters, and increased organ coefficients in the spleen, liver, heart, and kidneys. Toxicokinetics, tissue distribution, histopathological, and transmission electron microscopy analyses revealed that the spleen was the primary organ for IONPs elimination from the systemic circulation and that the macrophage lysosomes were the main organelles of IONPs accumulation after intravenous administration. We identified 197 upregulated and 75 downregulated proteins in the spleen following IONPs administration by proteomics. Mechanically, the AKT/mTOR/TFEB signaling pathway facilitated autophagy and lysosomal activation in splenic macrophages. This is the first study to elucidate the mechanism of IONPs toxicity by combining proteomics with traditional methods for toxicity assessment.
Topical nerve growth factor prevents neurodegenerative and vascular stages of diabetic retinopathy
Authors: Zerbini Gianpaolo , Maestroni Silvia , Leocani Letizia , Mosca Andrea , Godi Michela , Paleari Renata , Belvedere Arianna , Gabellini Daniela , Tirassa Paola , Castoldi Valerio , Viganò Ilaria , Galbiati Silvia , Turco Valentina , Lambiase Alessandro , Rama Paolo
Published: September 2022

Specific and effective preventive treatment for diabetic retinopathy (DR) is presently unavailable, mostly because the early stages of the complication have been, until recently, poorly understood. The recent demonstration that the vascular phase of DR is preceded and possibly caused by the neurodegeneration of retinal ganglion cells suggests that DR could, at least theoretically, be prevented through an early neuroprotective approach. The aims of our study were to clarify the natural history of diabetes-driven retinal neurodegeneration and to verify the possibility to prevent DR using topical nerve growth factor (NGF). The results of the study show that retinal neurodegeneration, characterized by the loss of retinal ganglion cells represents a relatively early phenomenon of diabetes (between 5 and 16 weeks of age), which tends to be self-limiting in the long run. Neurodegeneration is followed by the development of DR-related vascular dysfunctions, as confirmed by the development of acellular capillaries and the loss of retinal pericytes. Both retinal neurodegeneration and subsequent vascular dysfunction can be successfully prevented by topical NGF administration. These findings suggest that: 1) The first stage of DR consists in a self-limiting retinal neurodegeneration 2) The demonstrated effectiveness of topical NGF in the prevention of DR could be rapidly translated into clinical practice.
Schisandrin alleviates the cognitive impairment in rats with Alzheimer’s disease by altering the gut microbiota composition to modulate the levels of endogenous metabolites in the plasma, brain, and feces
Authors: Zhang Chengqin , Zhang Ying , Zhao Tiantian , Mou Tingting , Jing Wang , Chen Jian , Hao Wenqian , Gu Shuo , Cui Meirong , Sun Yue , Wei Binbin
Published: September 2022

Schisandrin is one of the main active compounds isolated from the fruit of Schisandrae chinensis Fructus, which is scientifically proven to have beneficial effects on Alzheimer’s disease (AD) treatment at the cellular and whole organism level. However, the oral availability of schisandrin is very low, thus implying that the underlying mechanism of therapeutic effect on AD treatment is yet to be clarified fully. Therefore, we speculated that the therapeutic effect of schisandrin on AD is mainly by regulating the imbalance of the gut microbiota (GM). In this study, behavioral experiments and H&E staining were used to confirm the pharmacological effects of schisandrin on rats with AD. 16S rDNA gene sequencing and feces, plasma, and brain metabolomics techniques were utilized to investigate the therapeutic effects and the underlying mechanisms of schisandrin on cognitive impairment in rats with AD. The results indicated that schisandrin improved cognitive impairment and hippocampal cell loss in rats. The UPLC-QTOF/MS-based metabolomics studies of the feces, plasma, and brain revealed that 44, 96, and 40 potential biomarkers, respectively, were involved in the treatment mechanism of schisandrin. Schisandrin improved the metabolic imbalance in rats with AD, and the metabolic changes mainly affected the primary bile acid biosynthesis, sphingolipid metabolism, glycerophospholipid metabolism, and unsaturated fatty acid biosynthesis. Schisandrin can improve the GM structure disorder and increase the abundance of beneficial bacteria in the gut of rats with AD. The predictive metagenomics analysis indicated that the altered GM was mainly involved in lipid metabolism, steroid hormone biosynthesis, arachidonic acid metabolism, biosynthesis of unsaturated fatty acids, and bacterial invasion of epithelial cells. Spearman’s correlation analysis showed a significant correlation between affected bacteria and metabolites in various metabolic pathways. Overall, the data underline that schisandrin improves the cognitive impairment in rats with AD by affecting the composition of the GM community, thus suggesting the potential therapeutic effect of schisandrin on the brain–gut axis in rats with AD at the metabolic level.
Patient-led development of digital endpoints and the use of computer vision analysis in assessment of motor function in rare diseases
Authors: Ferrer-Mallol Elisa , Matthews Clare , Stoodley Madeline , Gaeta Alessandra , George Elinor , Reuben Emily , Johnson Alex , Davies Elin Haf
Published: September 2022

Digital health technologies are transforming the way health outcomes are captured and measured. Digital biomarkers may provide more objective measurements than traditional approaches as they encompass continuous and longitudinal data collection and use of automated analysis for data interpretation. In addition, the use of digital health technology allows for home-based disease assessments, which in addition to reducing patient burden from on-site hospital visits, provides a more holistic picture of how the patient feels and functions in the real world. Tools that can robustly capture drug efficacy based on disease-specific outcomes that are meaningful to patients, are going to be key to the successful development of new treatments. This is particularly important for people living with rare and chronic complex conditions, where therapeutic options are limited and need to be developed using a patient-focused approach to achieve the biggest impact. Working in partnership with patient Organisation Duchenne UK, we co-developed a video-based approach, delivered through a new mobile health platform (DMD Home), to assess motor function in patients with Duchenne muscular dystrophy (DMD), a genetic, rare, muscular disease characterized by the progressive loss of muscle function and strength. Motor function tasks were selected to reflect the “transfer stage” of the disease, when patients are no longer able to walk independently but can stand and weight-bear to transfer. This stage is important for patients and families as it represents a significant milestone in the progression of DMD but it is not routinely captured and/or scored by standard DMD clinical and physiotherapy assessments. A total of 62 videos were submitted by eight out of eleven participants who onboarded the app and were analysed with pose estimation software (OpenPose) that led to the extraction of objective, quantitative measures, including time, pattern of movement trajectory, and smoothness and symmetry of movement. Computer vision analysis of video tasks to identify voluntary or compensatory movements within the transfer stage merits further investigation. Longitudinal studies to validate DMD home as a new methodology to predict progression to the non-ambulant stage will be pursued.
Mu opioid receptor stimulation in the medial preoptic area or nucleus accumbens facilitates song and reward in flocking European starlings
Authors: Polzin Brandon J. , Maksimoski Alyse N. , Stevenson Sharon A. , Zhao Changjiu , Riters Lauren V.
Published: September 2022

It has been proposed that social cohesion in gregarious animals is reinforced both by a positive affective state induced by social interactions and by the prevention of a negative state that would be caused by social separation. Opioids that bind to mu opioid receptors (MORs) act in numerous brain regions to induce positive and to reduce negative affective states. Here we explored a potential role for MORs in affective states that may impact flocking behavior in mixed-sex flocks of nonbreeding European starlings, Sturnus vulgaris. Singing behavior, which is considered central to flock cohesion, and other social behaviors were quantified after infusions of the MOR agonist D-Ala2, N-Me-Phe4, glycinol5-ENK (DAMGO) into either the medial preoptic area (POM) or the nucleus accumbens (NAC), regions previously implicated in affective state and flock cohesion. We focused on beak wiping, a potential sign of stress or redirected aggression in this species, to provide insight into a presumed negative state. We also used conditioned place preference (CPP) tests to provide insight into the extent to which infusions of DAMGO into POM or NAC that stimulated song might be rewarding. We found that MOR stimulation in either POM or NAC dose-dependently promoted singing behavior, reduced beak wiping, and induced a CPP. Subtle differences in responses to MOR stimulation between NAC and POM also suggest potential functional differences in the roles of these two regions. Finally, because the location of NAC has only recently been identified in songbirds, we additionally performed a tract tracing study that confirmed the presence of dopaminergic projections from the ventral tegmental area to NAC, suggesting homology with mammalian NAC. These findings support the possibility that MORs in POM and NAC play a dual role in reinforcing social cohesion in flocks by facilitating positive and reducing negative affective states.
Diethyl ether anesthesia induces transient cytosolic [Ca2+] increase, heat shock proteins, and heat stress tolerance of photosystem II in Arabidopsis
Authors: Pavlovič Andrej , Jakšová Jana , Kučerová Zuzana , Špundová Martina , Rác Marek , Roudnický Pavel , Mithöfer Axel
Published: September 2022

General volatile anesthetic diethyl ether blocks sensation and responsive behavior not only in animals but also in plants. Here, using a combination of RNA-seq and proteomic LC–MS/MS analyses, we investigated the effect of anesthetic diethyl ether on gene expression and downstream consequences in plant Arabidopsis thaliana. Differential expression analyses revealed reprogramming of gene expression under anesthesia: 6,168 genes were upregulated, 6,310 genes were downregulated, while 9,914 genes were not affected in comparison with control plants. On the protein level, out of 5,150 proteins identified, 393 were significantly upregulated and 227 were significantly downregulated. Among the highest significantly downregulated processes in etherized plants were chlorophyll/tetrapyrrole biosynthesis and photosynthesis. However, measurements of chlorophyll a fluorescence did not show inhibition of electron transport through photosystem II. The most significantly upregulated process was the response to heat stress (mainly heat shock proteins, HSPs). Using transgenic A. thaliana expressing APOAEQUORIN, we showed transient increase of cytoplasmic calcium level [Ca2+]cyt in response to diethyl ether application. In addition, cell membrane permeability for ions also increased under anesthesia. The plants pre-treated with diethyl ether, and thus with induced HSPs, had increased tolerance of photosystem II to subsequent heat stress through the process known as cross-tolerance or priming. All these data indicate that diethyl ether anesthesia may partially mimic heat stress in plants through the effect on plasma membrane.
Exploring mental health stigma among chinese-english bilinguals: Dual-process model of emotional competence, flipped learning readiness, and academic performance in Mainland Chinese Universities
Authors: Pei Lihua
Published: September 2022

Due to severe global competition and performance-related academic challenges, Chinese students are compelled to learn English and become bilinguals despite their non-English majors. Consequently, these students frequently experience psychological issues, including mental health stigma. Hence, the present study aims to explore the psychological factors associated with the academic performance of Chinese-English bilinguals as an outcome of their emotional competence, flipped learning readiness, and mental health stigma. Drawing on data from 448 Chinese-English bilingual students in universities in mainland China, the results based on structural equation modeling (SEM) indicated that their academic performance, flipped learning readiness, and emotional competence are negatively influenced by their mental health stigma. Moreover, the findings also validate that both flipped learning readiness and emotional competence significantly mediate the indirect effects of mental health stigma on the academic performance of bilinguals. The study's implications offer new and compelling evidence on the primary issue of mental health stigma among Gen Z bilingual students to raise deterrence against this psychological menace through collaboration across policymakers, academics, and mental healthcare providers.
Structural brain morphometry as classifier and predictor of ADHD and reward-related comorbidities
Authors: van Rooij Daan , Zhang-James Yanli , Buitelaar Jan , Faraone Stephen V. , Reif Andreas , Grimm Oliver
Published: September 2022

Attention deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders, and around two-thirds of affected children report persisting problems in adulthood. This negative trajectory is associated with high comorbidity with disorders like obesity, depression, or substance use disorder (SUD). Decreases in cortical volume and thickness have also been reported in depression, SUD, and obesity, but it is unclear whether structural brain alterations represent unique disorder-specific profiles. A transdiagnostic exploration of ADHD and typical comorbid disorders could help to understand whether specific morphometric brain changes are due to ADHD or, alternatively, to the comorbid disorders. In the current study, we studied the brain morphometry of 136 subjects with ADHD with and without comorbid depression, SUD, and obesity to test whether there are unique or common brain alterations. We employed a machine-learning-algorithm trained to classify subjects with ADHD in the large ENIGMA-ADHD dataset and used it to predict the diagnostic status of subjects with ADHD and/or comorbidities. The parcellation analysis demonstrated decreased cortical thickness in medial prefrontal areas that was associated with presence of any comorbidity. However, these results did not survive correction for multiple comparisons. Similarly, the machine learning analysis indicated that the predictive algorithm grouped most of our ADHD participants as belonging to the ADHD-group, but no systematic differences between comorbidity status came up. In sum, neither a classical comparison of segmented structural brain metrics nor an ML model based on the ADHD ENIGMA data differentiate between ADHD with and without comorbidities. As the ML model is based in part on adolescent brains, this might indicate that comorbid disorders and their brain changes are not captured by the ML model because it represents a different developmental brain trajectory.
GamReg Sweden—Protocol for a systematic cohort data collection for improved clinical knowledge in specialized gambling disorder treatment
Authors: Håkansson Anders , Åkesson Gunny
Published: September 2022

Background

Gambling disorder is the first non-substance-related addiction which is recognized as a diagnostic entity and assessed in treatment settings. However, in many clinical settings, assessment, and structured treatment for this condition is severely under-developed, and treatment seeking in many settings is low. This is a protocol paper describing the rationale and structure of a recently established quality register, allowing for structured monitoring of treatment seeking, treatment needs and treatment provision in Swedish health care settings, for gambling disorder and associated conditions.

Methods

Since 2019, a Swedish quality register is in use for the systematic data collection from patients receiving treatment in specialized health care. The register is held by Region Skåne, and approved for national use. Swedish quality registers allow for the clinical monitoring of treatment uptake and needs, for quality improvement purposes, and collect systematic cohort data for these purposes. In addition, these quality registers potentially allow for future research projects, after separate ethics applications, allowing for clinical follow-up studies based on non-identified quality register data. Clinical challenges and research knowledge gaps are addressed in the present register, including mental health comorbidity, history of suicidal behavior, comorbid alcohol, drugs and gaming behaviors, and fundamental psycho-social variables such as violence victimization, concerned significant others including children's situation in families of problem gamblers, and main income and involvements with social services and enforcement agency. In addition, patient flows, including rates of referral from primary care and other treatment settings, can be followed. The overall quality register project is registered at clinicaltrials.gov (NCT05276193).

Discussion

The present protocol paper will allow for systematic reporting and future projects addressing knowledge gaps in clinical treatment for gambling disorder, and highlight the importance for evidence-based treatment in a behavioral addiction. Importantly, the current data will contribute to a better understanding of which patient groups may be less likely to seek or to be referred to treatment, and thereby may shape future initiatives to increase screening and referral in targeted, vulnerable groups.
Data sharing in transboundary water management
Authors: Sarfaraz M. Umer , Hall Damon M. , Rotman Robin M.
Published: September 2022

Half the world's population resides within 310 transboundary lake and river basins shared among 151 riparian nations. Approximately 60% of these basins lack cooperative frameworks to share water. The complexities of sharing water necessitate identifying approaches for managing transboundary international freshwater resources. While much has been written about the histories, theory, and mechanisms of transboundary water management, conflict, and cooperation among riparian nations, we draw attention to scholarship written about what we believe is the central tool for cooperation: data and data sharing. The 1997 United Nations' Convention on the Law of the Non-Navigational Uses of International Watercourses (UN Watercourse Convention) recognizes sharing water resources data is vital to river basin cooperation. Data sharing builds trust between riparian states, aids in mitigating conflict, and improves environmental, economic, and social outcomes. Despite calls to increase data sharing in transboundary basins to support cooperative management, few papers review the role of data sharing in transboundary water management, including how often and what types of water resources data and information are shared. We synthesize the role of data in conflict and collaboration from peer-reviewed papers on transboundary water management from the year the UN Watercourse Convention went into force, 2014 to May 2022. We outline what scholars argue are the types of water-related data to be shared, the frequency of data sharing, and the mechanisms for sharing data for facilitating cooperation in transboundary waters.
Biocide treatment for mosquito control increases CH4 emissions in floodplain pond mesocosms
Authors: Ganglo Caroline , Manfrin Alessandro , Mendoza-Lera Clara , Lorke Andreas
Published: September 2022

Shallow lentic freshwater aquatic systems are globally important emitters of methane (CH4), a highly potent greenhouse gas. Previous laboratory studies indicated that bioturbation by chironomids can reduce CH4 production and increase CH4 oxidation by enhancing oxygen transport into sediment. Thus, reduction in chironomid density by application of biocides for mosquito control, such as Bacillus thuringinesis var. israelensis (Bti), have the potential to affect CH4 emissions. We evaluated the effect of a 41% reduction in chironomid larvae abundance due to Bti applications on CH4 dynamics in the aquatic and aquatic-terrestrial transition zones of 12 floodplain pond mesocosms (FPMs) (half treated, half control). We evaluated short-term (2 months) and seasonal effects by measuring CH4 emissions, dissolved concentrations, and oxidation rates in spring, summer, autumn, and winter. On average, CH4 emissions from the aquatic-terrestrial transition zone of the treated FPMs were 137 % higher than those of the control FPMs. The lack of differences in mean oxidation rates between the treated and control mesocosms suggests that a reduction in bioturbation and the associated decreased oxygen transport into the sediment promoted CH4 production in the treated FPMs. Our findings point to potential effects of Bti on CH4 biogeochemistry through alterations of the chironomid abundance, and highlight the underestimated role of invertebrates in biogeochemical cycling in these ecosystems.
Vector-based analysis of cortical activity associated with dumbbell exercise using functional near-infrared spectroscopy
Authors: Kato Toshinori
Published: September 2022

The mechanisms via which the brain and muscles work together remain poorly understood. The use of vector-based fNIRS, to propose a new metric and imaging method to understand neural activation during dumbbell-lifting exercises. This method can simultaneously measure oxyhemoglobin (oxyHb) and deoxyHb levels so that the angle k: Arctan (deoxyHb/oxyHb) represents the degree of oxygen exchange in the brain and can be used to quantify the distribution of oxygen consumption. The amplitude L of the vector reflects the intensity of the response caused by the amount of change in Hb. This study used vector-based fNIRS to simultaneously measure the left primary motor cortex (left M1), multiple peripheral regions, and the right biceps brachii muscle. The subjects were seven healthy adults. The task was a dumbbell-lifting exercise involving flexion and extension of the elbow joints of both arms. Dumbbell weights of 0 (no dumbbell), 4.5, and 9.5 kg were used. During dumbbell exercise, oxygen exchange increased in the left M1, indicating increased local oxygen consumption. Around the left M1, the cerebral oxygen exchange decreased, and oxygen supply increased without cerebral oxygen consumption. The spatial agreement between the maximum value of oxygen exchange k and L during the task was <20%. Therefore, the dumbbell-lifting exercise task study reported here supported the hypothesis that cerebral oxygen consumption associated with neural activation does not coincide with the distribution of cerebral oxygen supply. The relationship between the brain oxygen supply from the site of increased oxygen exchange in the brain and its surrounding areas can be quantified using the vector method fNIRS.
Rumen-protected zinc–methionine dietary inclusion alters dairy cow performances, and oxidative and inflammatory status under long-term environmental heat stress
Authors: Danesh Mesgaran Mohsen , Kargar Hassan , Janssen Rieke , Danesh Mesgaran Sadjad , Ghesmati Aghil , Vatankhah Amirmansour
Published: September 2022

Dairy cows are susceptible to heat stress due to the levels of milk production and feed intake. Dietary supplemental amino acids, particularly rate-limiting amino acids, for example, methionine (Met), may alleviate the potential negative consequences. Zinc (Zn) is beneficial to the immune system and mammary gland development during heat stress. We investigated the impact of a source of a rumen-protected Zn-Met complex (Loprotin, Kaesler Nutrition GmbH, Cuxhaven, Germany) in high-producing Holstein cows during a long-term environmental heat stress period. A total of 62 multiparous lactating Holstein cows were allocated in a completely randomized design to two dietary treatments, namely, basal diet without (control) and basal diet with the supplemental Zn-Met complex (RPZM) at 0.131% of diet DM. Cows in the RPZM group had higher energy-corrected milk (46.71 vs. 52.85 ± 1.72 kg/d for control and RPZM groups, respectively) as well as milk fat and protein concentration (27.28 vs. 32.80 ± 1.82 and 30.13 vs. 31.03 ± 0.25 g/kg for control and RPZM groups, respectively). The Zn-Met complex supplemented cows had lower haptoglobin and IL-1B concentration than the control (267 vs. 240 ± 10.53 mcg/mL and 76.8 vs. 60.0 ± 3.4 ng/L for control and RPZM groups, respectively). RPZM supplementation resulted in better oxidative status, indicated by higher total antioxidant status and lower malondialdehyde concentrations (0.62 vs. 0.68 ± 0.02 mmol/L and 2.01 vs. 1.76 ± 0.15 nmol/L for control and RPZM groups, respectively). Overall, the results from this study showed that RPZM dietary inclusion could maintain milk production and milk composition of animals during periods of heat stress. Enhanced performance of animals upon Zn-Met complex supplementation could be partly due to improved oxidative and immune status.
Éjszakai bruxizmus és erózió okozta fogkopás esztétikai rehabilitációja
Authors: Laki-Czigola Alexandra , Borbély Judit , Hermann Péter
Published: September 2022

Magas esztétikai igényű fiatal női páciensünk esetén nagy kihívást jelent a bruxizmus és savas erózió okozta fogkopásteljes szájüregi rehabilitációja. Ha a fogkopás csak a frontfogakra és kísőrlőkre terjed ki, a rendelkezésre álló kicsi interokkluzális tér nem biztosítja a megfelelő helyet a frontfogak eredeti magasságának helyreállítására, így az esztétikai rehabilitációnk során a vertikális harapási magasság helyreállítása is megtörtént. Fontos a kiszámítható és temporomandibuláris ízületre kiterjedő gondos kezelési terv készítése, melyhez a digitális technológiák a mosolytervezés, a fordított tervezés, azaz a backward planning és a 2 hónapig viselt funkcionális ideiglenes fogpótlások másolása (copy paste dentistry) során voltak segítségünkre. A harapásemelés mértékének megállapításához hagyományos intraorális rajzolókészüléket alkalmaztunk, és a végleges fogpótlás minimálinvazív preparációt követően, magas esztétikájú monolitikus üvegkerámiából készült el.