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Dougho Park,1 Byung Hee Kim,1 Sang-Eok Lee,1 Dong Young Kim,2 Yoon Sik Eom,2 Jae Man Cho,3 Joong Won Yang,3 Mansu Kim,3 Heum Dai Kwon3 1Department of Rehabilitation Medicine, Spine and Joint Center, Pohang Stroke and Spine Hospital, Pohang, Republic of Korea; 2Department of Orthopedic Surgery, Spine and Joint Center, Pohang Stroke and Spine Hospital, Pohang, Republic of Korea; 3Department of Neurosurgery, Spine and Joint Center, Pohang Stroke and Spine Hospital, Pohang, Republic of KoreaCorrespondence: Dougho ParkDepartment of Rehabilitation Medicine, Spine and Joint Center, Pohang Stroke and Spine Hospital, 352, Huimang-Daero, Nam-Gu, Pohang, 37659, Republic of KoreaTel +82 54 289 9171Fax +82 54 289 9100Email parkdougho@gmail.comPurpose: A bifid median nerve (BMN) is not a rare variant. This study aimed to investigate the features of carpal tunnel syndrome (CTS) accompanied by BMN.Patients and Methods: In this retrospective study, we defined a BMN group as CTS with BMN and a non-bifid median nerve (NMN) group as CTS without BMN. All hands were assigned to four severity grades according to the findings of electrodiagnosis (EDx): very mild, mild, moderate, and severe. The cross-sectional area (CSA) of the median nerve, palmar bowing of the flexor retinaculum, and persistent median artery (PMA) were assessed by ultrasonography. Numerical pain rating scale (NRS) and symptom duration were assessed as clinical variables.Results: Sixty-four hands (57 patients) and 442 hands (341 patients) were enrolled in the BMN and the NMN groups, respectively. BMN was prevalent in 12.6% of all CTS hands. The distribution of EDx severity grade was milder in the BMN group than in the NMN group (P< 0.001). The CSA of the BMN group was 16.2± 4.1 mm2, slightly larger than 15.1± 4.2 mm2 in the NMN group (P=0.056). The BMN group showed higher NRS than the NMN group (5.5± 1.5 and 4.4± 1.7, respectively; P< 0.001). In the subgroup analysis, NRS was significantly higher in the BMN group than in the NMN group at all EDx severity grades. In the BMN group, the PMA group showed greater EDx severity (P=0.037) and higher NRS (6.0 and 5.0, respectively; P=0.012) than the non-PMA group. The radial side branch’s CSA was larger than that of the ulnar side branch (10.0 mm2 and 6.0 mm2, respectively; P< 0.001).Conclusion: CTS with BMN presented more severe symptoms and relatively milder EDx severity. When assessing the severity of CTS with BMN, the clinical symptoms should primarily be considered, as well as we should complementarily evaluate the EDx and ultrasonography.Keywords: carpal tunnel syndrome, bifid median nerve, electrodiagnosis, diagnostic ultrasound, pain measurement

Na Zhang,1,2 Li-Qiong Wang,1 Jin-Ling Li,1 Xin-Tong Su,1 Fang-Ting Yu,1 Guang-Xia Shi,1 Jing-Wen Yang,1 Cun-Zhi Liu1 1International Acupuncture and Moxibustion Innovation Institute, School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2School of Acupuncture-Moxibustion and Tuina, Shandong University of Chinese Medicine, Shandong, People’s Republic of ChinaCorrespondence: Cun-Zhi LiuSchool of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Lu, Chaoyang District, Beijing 100029, People’s Republic of ChinaEmail lcz_tg@126.comObjective: Acupuncture therapy is an effective non-drug therapy for sciatica, but it has not yet formed an effective treatment strategy and recommendations. Our objective was to establish an expert consensus on acupuncture treatment of sciatica for clinical guidance based on the improved Delphi survey.Methods: A group of 80 clinical specialists was invited to participate in two rounds of semi-open clinical issue investigation. At the same time, the PubMed, Embase, and Cochrane Library databases were searched for systematic reviews on acupuncture treatment of sciatica, and the quality of evidence was evaluated. Then the three-round Delphi survey was undertaken with 30 experts based on the clinical issue investigation and systematic reviews.Results: In round 1 of the Delphi survey, the experts evaluated 17 items identified from the results of the clinical investigation and literature review. The criterion for achieving consensus was a threshold of 80% agreement. After the three-round Delphi survey, 16 items (94.12%) achieved consensus, including 5 domains: the principle of acupuncture treatment for sciatica; the “dose” of acupuncture; the clinical effects of acupuncture; the adverse effects, and others.Conclusion: This Delphi survey achieved an expert consensus on key items in the management of sciatica for acupuncture, which provides the current opinions in China. We trust that these treatment recommendations may facilitate their implementation in the future.Keywords: acupuncture, sciatica, expert consensus, Delphi survey

Guang-Xia Shi,1 Jian-Feng Tu,2 Tian-Qi Wang,2 Jing-Wen Yang,2 Li-Qiong Wang,2 Lu-Lu Lin,2 Yu Wang,1 Yong-Ting Li,1 Cun-Zhi Liu2 1Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing, People’s Republic of China; 2School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaCorrespondence: Cun-Zhi Liu Email lcz_tg@126.comBackground: Inflammation plays a significant role in the pathogenesis of knee osteoarthritis (KOA). Although both electro-acupuncture (EA) and manual acupuncture (MA) are known to influence systemic inflammation, little is known about the potential changes in inflammation as a working mechanism of EA and MA in KOA.Methods: Data from the Acupuncture for Knee Osteoarthritis Trial (ATKOA) were used. Serum concentrations of inflammatory factors (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-8, IL-18, IL-4, IL-10, IL-13, IL-15, IL-17, monocyte chemotactic protein-1 (MCP-1), CC-chemokine ligand 5 (CCL5), and cartilage degradation biomarkers (matrix metalloproteinase-1 MMP-1, MMP-3, MMP-13 and cartilage oligomeric matrix protein COMP)) were measured at baseline and after 8 weeks of treatment. Clinical outcomes were valid and reliable self-reported pain and function measures for osteoarthritis using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and visual analogue scale (VAS) at baseline and post-treatment.Results: Both 8-weeks EA and MA significantly reduced pro-inflammatory cytokines (TNFα, IL-1β), and cartilage degradation biomarkers (MMP-3, MMP-13) significantly increased the anti-inflammatory cytokine IL-13 compared with pre-treatment (p< 0.05). Further, the reduction of TNF-α was more significant in EA when compared to MA (p=0.046). While there was no significant difference between groups in cytokines IL-1β (p=0.102), MMP-3 (p=0.113), MMP-13 (p=0.623) or IL-13 (p=0.935). Moreover, in both EA and MA, the effect of acupuncture on the VAS and WOMAC function scale after 8 weeks is clinically important, although no significant differences were found between groups.Conclusion: Eight weeks of both EA and MA seem to provide improvement in pain relief and function among individuals with mild to moderate knee OA. This benefit is partly mediated by changes of major inflammatory factors TNF-α, IL-1β and IL-13.Trial Registration: Controlled-Trials.com Identifier: NCT03274713.Keywords: knee osteoarthritis, electro-acupuncture, manual acupuncture, inflammation

Ha Na Oh,1 Joo Eun Lee,2 Hyun Woong Kim,1 Jae Wook Yang,1 Il Han Yun11Department of Ophthalmology, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea; 2Department of Ophthalmology, Haeundae Paik Hospital, Inje University College of Medicine, Busan, KoreaPurpose: To report on a case that developed an atypical form of occult choroidal neovascularization (CNV) after successful macular hole surgery.Methods: Visual acuity change, color fundus photographs, fluorescein and indocyanine green angiograms, and optical coherence tomography results were compared throughout the follow-up duration.Patients: A 64-year-old woman with a macular hole in the right eye and drusen in both eyes underwent pars plana vitrectomy, internal limiting membrane peeling, and gas tamponade. One month after the operation she developed occult CNV, in which pigment epithelial detachment and fine retinal pigment epithelial (RPE) layer wrinkles were observed under the completely sealed macular hole. After 3-monthly intravitreal injections of ranibizumab, the lesion did not change significantly.Conclusion: CNV can develop after otherwise successful macular hole surgery, especially in patients with pre-existing aging changes in the macula, such as drusen. Care should be taken in such patients, to prevent the development of CNV after macular hole surgery.Keywords: drusen, macular hole surgery, occult choroidal neovascularization, ranimizumab injection

Background and Objectives: Between 1998 and 2000, approximately 525 Tibetan people previously living in the United States claimed refugee status in Canada, many of whom were referred to our centers for completion of tuberculosis (TB) screening. We reviewed TB-related outcomes in this cohort, to compare our experience with previously published work, and to assess follow-up after a stay in a low-incidence region.Methods: We performed a retrospective study of all patients of Tibetan origin assessed at our centers (St. Michael's Hospital and West Park Healthcare Centre, both in Toronto) for completion of TB screening, referred because of abnormal chest radiographic findings or positive tuberculin skin test (TST) result. We compared rates of active and drug-resistant TB in our cohort with local and national rates, as well as those previously published in similar groups.Results: One hundred eighty-nine individuals were referred to us for assessment, and 181 records were available for review. The mean duration of stay in Canada prior to presentation was 2.6 months, after having spent a mean of 11 months in the United States. Thirty-two percent of patients gave a history of previous TB, and 97% were TST positive. Culture-positive TB was diagnosed in 24 patients (13%, 4,571 per 100,000), 12 patients had at least one drug resistance (50% of cases), and 4 patients were resistant to at least isoniazid and rifampin (multidrug resistant, 17% of cases).Interpretation: People from highly TB endemic areas retain a very high risk of active TB and drug resistance, despite an intervening period in a low-prevalence country. It is important to maintain a high degree of suspicion for TB in all people from high-incidence areas. Treatment of all cases of latent TB infection or ongoing medical surveillance is likely justified in this population. [ABSTRACT FROM AUTHOR]

Graphene oxide (GO) is a two-dimensional metastable nanomaterial. Interestingly, GO formed oxygen clusterings in addition to oxidized and graphitic phases during the low-temperature thermal annealing process, which could be further used for biomolecule bonding. By harnessing this property of GO, we created a bio-interface with patterned structures with a common laboratory hot plate that could tune cellular behavior by physical contact. Due to the regional distribution of oxygen clustering at the interface, we refer to it as patterned annealed graphene oxide (paGO). In addition, since the paGO was a heterogeneous interface and bonded biomolecules to varying degrees, arginine-glycine-aspartic acid (RGD) was modified on it and successfully regulated cellular-directed growth and migration. Finally, we investigated the FRET phenomenon of this heterogeneous interface and found that it has potential as a biosensor. The paGO interface has the advantages of easy regulation and fabrication, and the one-step thermal reduction method is suitable for biological applications. We believe that this low-temperature thermal annealing method would make GO interfaces more accessible, especially for the development of nano-interfacial modifications for biological applications, revealing its potential for biomedical applications.

Background: Molecular and transcription factor subtyping were recently introduced to identify patients with unique clinical features in small cell lung cancer (SCLC). However, its prognostic relevance is yet to be established. This study aims to investigate the clinical implications and prognostic significance of transcription factor subtyping in SCLC using immunohistochemistry., Methods: One hundred and ninety consecutive SCLC patients treated with platinum-based chemotherapy at a single institution were retrospectively reviewed. Expression of ASCL1, NeuroD1, POU2F3, and YAP1 was assessed by immunohistochemical staining and applied to determine the transcription factor subtype of each case., Results: The association among transcription factors was not entirely mutually exclusive. YAP1 expression was the most significant prognostic indicator compared with other transcription factors or their related subtypes. Among patients with limited-stage disease (LD), complete response (CR) rates were 46.2% and 22.4% in the YAP1-positive and YAP1-negative groups, respectively. The median duration of response among patients who achieved CR was 64.8 and 36.4 months in the YAP1-positive and YAP1-negative groups, respectively (P=0.06). Median overall survival (OS) in LD was 35.6 and 16.9 months in the YAP1-positive and YAP1-negative groups, respectively (P=0.03). In extensive-stage disease (ED), the median OS was 11.3 months for the YAP1-positive group and 11 months for the YAP1-negative group (P=0.03)., Conclusions: Positive expression of YAP1 can be associated with durable CR and favorable survival outcomes in patients with SCLC, especially in LD., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-317/coif). The authors have no conflicts of interest to declare., (2024 Translational Lung Cancer Research. All rights reserved.)

Drug toxicity assays using conventional 2D static cultures and animal studies have limitations preventing the translation of potential drugs to the clinic. The recent development of organs-on-a-chip platforms provides promising alternatives for drug toxicity/screening assays. However, most studies conducted with these platforms only utilize single endpoint results, which do not provide real-time/ near real-time information. Here, a versatile technology is presented that integrates a 3D liver-on-a-chip with a label-free photonic crystal-total internal reflection (PC-TIR) biosensor for rapid and continuous monitoring of the status of cells. This technology can detect drug-induced liver toxicity by continuously monitoring the secretion rates and levels of albumin and glutathione S-transferase α (GST-α) of a 3D liver on-a-chip model treated with Doxorubicin. The PC-TIR biosensor is based on a one-step antibody functionalization with high specificity and a detection range of 21.7 ng mL -1 to 7.83 x 10 3  ng mL -1 for albumin and 2.20 ng mL -1 to 7.94 x 10 2  ng mL -1 for GST-α. This approach provides critical advantages for the early detection of drug toxicity and improved temporal resolution to capture transient drug effects. The proposed proof-of-concept study introduces a scalable and efficient plug-in solution for organ-on-a-chip technologies, advancing drug development and in vitro testing methods by enabling timely and accurate toxicity assessments., (© 2024 Wiley‐VCH GmbH.)

Objectives: To investigate the clinical and genetic features of children with 3-methylcrotonyl-coenzyme A carboxylase deficiency (MCCD)., Methods: A retrospective analysis was conducted on the clinical manifestations and genetic testing results of six children with MCCD who attended Children's Hospital Affiliated to Zhengzhou University from January 2018 to October 2023., Results: Among the six children with MCCD, there were 4 boys and 2 girls, with a mean age of 7 days at the time of attending the hospital and 45 days at the time of confirmed diagnosis. Of all children, one had abnormal urine odor and five had no clinical symptoms. All six children had increases in blood 3-hydroxyisovaleryl carnitine and urinary 3-hydroxyisovaleric acid and 3-methylcrotonoylglycine, and five of them had a reduction in free carnitine. A total of six mutations were identified in the MCCC1 gene, i.e., c.1630del(p.R544Dfs*2), c.269A>G(p.D90G), c.1609T>A(p.F537I), c.639+2T>A, c.761+1G>T, and c.1331G>A(p.R444H), and three mutations were identified in the MCCC2 gene, i.e., c.838G>T(p.D280Y), c.592C>T(p.Q198*,366), and c.1342G>A(p.G448A). Among these mutations, c.269A>G(p.D90G) and c.1609T>A(p.F537I) had not been previously reported in the literature. There was one case of maternal MCCD, and the child carried a heterozygous mutation from her mother. Five children with a reduction in free carnitine were given supplementation of L-carnitine, and free carnitine was restored to the normal level at the last follow-up visit., Conclusions: This study identifies two new mutations, c.269A>G(p.D90G) and c.1609T>A(p.F537I), thereby expanding the mutation spectrum of the MCCC1 gene. A combination of blood amino acid and acylcarnitine profiles, urine organic acid analysis, and genetic testing can facilitate early diagnosis and treatment of MCCD, and provide essential data for genetic counseling.

Micro-light-emitting diodes (μLEDs) have gained significant interest as an activation source for gas sensors owing to their advantages, including room temperature operation and low power consumption. However, despite these benefits, challenges still exist such as a limited range of detectable gases and slow response. In this study, we present a blue μLED-integrated light-activated gas sensor array based on SnO 2 nanoparticles (NPs) that exhibit excellent sensitivity, tunable selectivity, and rapid detection with micro-watt level power consumption. The optimal power for μLED is observed at the highest gas response, supported by finite-difference time-domain simulation. Additionally, we first report the visible light-activated selective detection of reducing gases using noble metal-decorated SnO 2 NPs. The noble metals induce catalytic interaction with reducing gases, clearly distinguishing NH 3 , H 2 , and C 2 H 5 OH. Real-time gas monitoring based on a fully hardware-implemented light-activated sensing array was demonstrated, opening up new avenues for advancements in light-activated electronic nose technologies., (© 2024. The Author(s).)

Background: Targeted therapies for diabetic nephropathy (DN) are lacking, partly due to their irreversible nature. The role of Orai1, a store-operated Ca2+ channel, in DN remains debated, with conflicting evidence on its effect on proteinuria in animal models. We aimed to elucidate the functional relevance of Orai1 expression for clinicopathological parameters in patients with DN., Methods: In this study, we included 93 patients diagnosed with DN between 2009 and 2019. Immunohistochemical staining for Orai1 was performed on paraffin-embedded kidney sections. The significance of Orai1 expression in human DN was assessed by examining its correlation with DN's pathological and clinical parameters using Pearson's correlation coefficient and univariate logistic regression., Results: Orai1 was significantly overexpressed in DN patients compared to control. A strong correlation was observed between increased Orai1 expression and higher Renal Pathology Society DN classification, enhanced interstitial fibrosis and tubular atrophy scores. Positive correlations with serum creatinine levels and prognosis of chronic kidney disease (CKD) by glomerular filtration rate (GFR) and albuminuria category were noted but the estimated GFR was inversely related to Orai1 expression. Orai1's association with advanced CKD stages persisted even after adjusting for confounding variables in multivariate logistic regression analysis., Conclusion: Orai1 expression is closely associated with histological and clinical severities of DN, suggesting its potential as a predictive biomarker for disease progression and prognosis. These findings provide new perspectives on therapeutic interventions targeting Orai1 in DN.

Purpose: To evaluate the structural, microvascular, and functional progression of normal tension glaucoma (NTG) with or without high myopia by examining longitudinal changes in optical coherence tomography angiography (OCTA) and visual field (VF) parameters., Methods: We evaluated 61 NTG eyes and classified 25 of the eyes with axial lengths (ALs) of ≥26 mm as highly myopic. We assessed the rate of change in OCTA parameters, namely radial peripapillary capillary (RPC) vessel density (VD), parafovea VD, deep parafovea VD, retinal nerve fibre layer (RNFL) thickness, and ganglion cell complex thickness. We evaluated the correlation of the rate of change in OCTA parameters with VF loss and AL., Results: Among the 61 NTG eyes, rates of loss of RPC VD, parafovea VD, deep parafovea VD, and RNFL thickness were significantly different from zero despite the nonsignificant rate of change in VF mean deviation (MD). Changes in these OCTA parameters did not differ significantly in highly myopic NTG eyes. The rate of change in VF MD was significantly correlated with the rate of change in parafovea VD in highly myopic and non-highly myopic NTG eyes. In highly myopic NTG eyes, AL was negatively correlated with the rates of loss of RNFL thickness, VF MD, and VF PSD., Conclusion: NTG eyes with a relatively stable VF exhibited loss of VD and RNFL thickness. VF progression in NTG was correlated with decreasing parafovea VD, indicating a structure-function correlation. Greater AL may indicate faster VF loss and RNFL thinning in highly myopic NTG eyes., (© 2024 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background and Purpose: The analgesic action of paracetamol involves K V 7 channels, and its metabolite N-acetyl-p-benzo quinone imine (NAPQI), a cysteine modifying reagent, was shown to increase currents through such channels in nociceptors. Modification of cysteine residues by N-ethylmaleimide, H 2 O 2 , or nitric oxide has been found to modulate currents through K V 7 channels. The study aims to identify whether, and if so which, cysteine residues in neuronal K V 7 channels might be responsible for the effects of NAPQI., Experimental Approach: To address this question, we used a combination of perforated patch-clamp recordings, site-directed mutagenesis, and mass spectrometry applied to recombinant K V 7.1 to K V 7.5 channels., Key Results: Currents through the cardiac subtype K V 7.1 were reduced by NAPQI. Currents through all other subtypes were increased, either by an isolated shift of the channel voltage dependence to more negative values (K V 7.3) or by such a shift combined with increased maximal current levels (K V 7.2, K V 7.4, K V 7.5). A stretch of three cysteine residues in the S2-S3 linker region of K V 7.2 was necessary and sufficient to mediate these effects., Conclusion and Implication: The paracetamol metabolite N-acetyl-p-benzo quinone imine (NAPQI) modifies cysteine residues of K V 7 subunits and reinforces channel gating in homomeric and heteromeric K V 7.2 to K V 7.5, but not in K V 7.1 channels. In K V 7.2, a triple cysteine motif located within the S2-S3 linker region mediates this reinforcement that can be expected to reduce the excitability of nociceptors and to mediate antinociceptive actions of paracetamol., (© 2024 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Objective: Converging evidence indicates that subjective cognitive decline (SCD) could be an early indicator of dementia. The hippocampus is the earliest affected region during the progression of cognitive impairment. However, little is known about whether and how acupuncture change the hippocampal structure and function of SCD individuals., Methods: Here, we used multi-modal MRI to reveal the mechanism of acupuncture in treating SCD. Seventy-two older participants were randomized into acupuncture or sham acupuncture group and treated for 12 weeks., Results: At the end of the intervention, compared to sham acupuncture, participants with acupuncture treatment showed improvement in composite Z score from multi-domain neuropsychological tests, as well as increased hippocampal volume and functional connectivity. Moreover, the greater white matter integrity of the fornix, which is the major output tract of the hippocampus, was shown in the acupuncture group., Conclusion: These findings suggest that acupuncture may improve the cognitive function of SCD individuals, and increase hippocampal volume on the regional level and enhance the structural and functional connectivity of hippocampus on the connective level., Competing Interests: DISCLOSURES The authors report no conflicts with any product mentioned or concept discussed in this article., (Copyright © 2024 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Patient-derived organoids (PDOs) developed ex vivo and in vitro are increasingly used for therapeutic screening. They provide a more physiologically relevant model for drug discovery and development compared to traditional cell lines. However, several challenges remain to be addressed to fully realize the potential of PDOs in therapeutic screening. This paper summarizes recent advancements in PDO development and the enhancement of PDO culture models. This is achieved by leveraging materials engineering and microfabrication technologies, including organs-on-a-chip and droplet microfluidics. Additionally, this work discusses the application of PDOs in therapy screening to meet diverse requirements and overcome bottlenecks in cancer treatment. Furthermore, this work introduces tools for data processing and analysis of organoids, along with their microenvironment. These tools aim to achieve enhanced readouts. Finally, this work explores the challenges and future perspectives of using PDOs in drug development and personalized screening for cancer patients., (© 2024 Wiley‐VCH GmbH.)

Golden pompano is an important aquaculture product in the coastal regions of southern China, which is highly dependent on insulin-like growth factor (IGF) for various biological processes. The cDNAs of ToIGF1, ToIGF2, and ToIGF3 are 1718 bp, 1658 bp, and 2272 bp in length, respectively, with corresponding amino acid sequences of 185 aa, 215 aa, and 194 aa. These sequences consist of 5 parts, including the signal peptide, the B domain, the C domain, the A domain, the D domain, and the E domain, which are also found in other species. While ToIGF1 has no SSR polymorphism, ToIGF2 and ToIGF3 have 3 and 1 SSR polymorphism sites, respectively. In terms of tissue expression, ToIGF1 is predominantly expressed in the liver, ToIGF2 shows its highest expression in the gills, and ToIGF3 also shows its highest expression in the gills, but no expression in the liver and spleen. These tissue distribution results suggest that ToIGFs are not only present in growth-related tissues such as the brain, muscle, and liver, but also in reproductive tissues, tissues that regulate osmotic pressure, and tissues related to food intake. This observation is consistent with other bony fish species and highlights the extensive biological functions of ToIGFs that need to be further explored and exploited. In addition, the expression levels of ToIGFs were found to be different in the different dietary groups, including the pelleted food group, the frozen squid group, and the frozen fish group. In the pelleted diet group, ToIGF1 and ToIGF2 were highly expressed in the liver and intestinal tissues, followed by the frozen fish group. These results suggest that the type of diet can affect the body's energy metabolism by influencing tissue expression of growth-related genes, which in turn affects individual growth., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: The significant rebound of influenza A (H1N1) virus activity, particularly among children, with rapidly growing number of hospitalized cases is of major concern in the post-COVID-19 era. The present study was performed to establish a prediction model of severe case in pediatric patients hospitalized with H1N1 infection during the post-COVID-19 era., Methods: This is a multicenter retrospective study across nine public tertiary hospitals in Yunnan, China, recruiting pediatric H1N1 inpatients hospitalized at five of these centers between February 1 and July 1, 2023, into the development dataset. Screening of 40 variables including demographic information, clinical features, and laboratory parameters were performed utilizing Least Absolute Shrinkage and Selection Operator (LASSO) regression and logistic regression to determine independent risk factors of severe H1N1 infection, thus constructing a prediction nomogram. Receiver operating characteristic (ROC) curve, calibration curve, as well as decision curve analysis (DCA) were employed to evaluate the model's performance. Data from four independent cohorts comprised of pediatric H1N1 inpatients from another four hospitals between July 25 and October 31, 2023, were utilized to externally validate this nomogram., Results: The development dataset included 527 subjects, 122 (23.1 %) of whom developed severe H1N1 infection. The external validation dataset included 352 subjects, 72 (20.5 %) of whom were eventually confirmed as severe H1N1 infection. The LASSO regression identified 19 candidate predictors, with logistic regression further narrowing down to 11 independent risk factors, including underlying conditions, prematurity, fever duration, wheezing, poor appetite, leukocyte count, neutrophil-lymphocyte ratio (NLR), erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α). By integrating these 11 factors, a predictive nomogram was established. In terms of prediction of severe H1N1 infection, excellent discriminative capacity, favorable accuracy, and satisfactory clinical usefulness of this model were internally and externally validated via ROC curve, calibration curve, and DCA, respectively., Conclusion: Our study successfully established and validated a novel nomogram model integrating underlying conditions, prematurity, fever duration, wheezing, poor appetite, leukocyte count, NLR, ESR, LDH, IL-10, and TNF-α. This nomogram can effectively predict the occurrence of serious case in pediatric H1N1 inpatients during the post-COVID-19 era, facilitating the early recognition and more efficient clinical management of such patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Chronic neuropathic pain has been one of the prominent causes of disability, and acupuncture has shown promise in treatment. The present study aimed to characterize acupuncture modulation of chronic neuropathic pain and explore the related functional brain changes. Sixty chronic sciatica patients were divided into acupuncture- or sham acupuncture groups and received 10 sessions of treatment during 4 weeks. The visual analog scale for leg pain, oswestry disability index (ODI), and resting-state functional magnetic resonance images were assessed at baseline and after treatment. Then, fractional amplitudes of low-frequency fluctuations (fALFF) and support vector regression analyses were performed. Compared with sham acupuncture, acupuncture significantly improved symptoms, including visual analog scale for leg pain and ODI. In addition, acupuncture exhibited increased fALFF of the right superior parietal lobule (SPL) and right postcentral gyrus. Furthermore, the actual 4-week ODI values were positively correlated with the support vector regression-predicted values based on the right SPL fALFF and baseline clinical measurements. These results indicate that the spontaneous neural activity of the right SPL and right postcentral gyrus may be involved in the modulation of acupuncture in chronic neuropathic pain. In addition, the spontaneous neural activity of the right SPL might be used as the predictor of response to acupuncture therapy. PERSPECTIVE: This clinical neuroimaging study elucidated the neural basis of acupuncture in chronic sciatica. Neurological indicators and clinical measurements could be used as potential predictors of acupuncture response. This study combines neuroimaging and artificial intelligence techniques to highlight the potential of acupuncture for the treatment of chronic neuropathic pain. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry, ChiCTR2100044585, http://www.chictr.org.cn., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To explore the correlation between blastomere count variations "skip value" which extracted from by time-lapse technology (TLT) combined with artificial intelligence (AI) and morphological features of in vitro fertilization (IVF) embryo, and to test its feasibility in clinical applications. Methods: This study was a diagnostic experiment (AI reassessment of embryo transferred patients), a total of 6 545 embryos from 1 226 patients who underwent IVF at the Women and Children's Hospital of Chongqing Medical University from December 2020 to December 2021 were retrospectively analyzed, of which 2 869 embryos were attempted to cultured to blastocyst stage by TLT. The embryo dynamic map (EDM) was drawn by Embryo Viewer, a TLT recording software, based on embryo developmental kinetics. The self-developed AI embryo evaluation software identified and recorded the number of cleavages in real time during embryonic development, and compared with the EDM, the correlation between the skip value formed by the change of cleavage sphere counts and the outcomes of the embryos was analyzed. The correlation among skip value, morphological score of embryo, implantation rate and live birth rate were performed by Spearman and step-up logistic regression. The receiver operating characteristic (ROC) curve was selected for reporting there relationship of skip value and morphology. Finally, predicting power of skip value for implantation and live birth rate were performed by ROC analysis. Results: The total skip values extracted from the blastomere count of embryos (72 hours post-fertilization) were negatively correlated with abnormal cleavage, blastocyst formation rate, day 3 (D3)-cell score, uneven size and fragmentation (the β values were -0.268, -0.116, -0.213, -0.159 and -0.222, respectively; all P <0.001); positively correlated with D3-cell number ( β =0.034; P <0.001); negatively correlated with blastocyst formation rate and implantation rate ( OR =0.97, 95% CI : 0.93-0.99, P =0.034; OR =0.96, 95% CI : 0.93-0.98, P =0.044). The power of predicting implantation were similar between the order selection of skip values and traditional morphology criteria [area under curve (AUC): 0.679 vs 0.620]. Live birth rate were negatively correlated with female age ( OR =0.91, 95% CI : 0.88-0.93; P <0.001), D3 general score ( OR =0.77, 95% CI : 0.59-0.99; P =0.045) and order selection of skip values ( OR =0.98, 95% CI : 0.96-0.99; P =0.038), while positively correlated with retrieved oocyte number and endometrial thickness in embryo transferred ( OR =1.08, 95% CI :1.05-1.11, P <0.001; OR =1.09, 95% CI :1.06-0.12, P <0.001, respectively) from multivariate regression analysis, and the power of predicting live birth was 0.666 for AUC. Conclusions: The skip value and its order form is a systematic quantification of embryo development, correlated with embryo developmental quality and clinical outcome. It could be an addition parameter for embryo culture and selection.

Human Accelerated Regions (HARs) are highly conserved across species but exhibit a significant excess of human-specific sequence changes, suggesting they may have gained novel functions in human evolution. HARs include transcriptional enhancers with human-specific activity and have been implicated in the evolution of the human brain. However, our understanding of how HARs contributed to uniquely human features of the brain is hindered by a lack of insight into the genes and pathways that HARs regulate. It is unclear whether HARs acted by altering the expression of gene targets conserved between HARs and their chimpanzee orthologs or by gaining new gene targets in human, a mechanism termed enhancer hijacking. We generated a high-resolution map of chromatin interactions for 1,590 HARs and their orthologs in human and chimpanzee neural stem cells (NSCs) to comprehensively identify gene targets in both species. HARs and their chimpanzee orthologs targeted a conserved set of 2,963 genes enriched for neurodevelopmental processes including neurogenesis and synaptic transmission. Changes in HAR enhancer activity were correlated with changes in conserved gene target expression. Conserved targets were enriched among genes differentially expressed between human and chimpanzee NSCs or between human and non-human primate developing and adult brain. Species-specific HAR gene targets did not converge on known biological functions and were not significantly enriched among differentially expressed genes, suggesting that HARs did not alter gene expression via enhancer hijacking. HAR gene targets, including differentially expressed targets, also showed cell type-specific expression patterns in the developing human brain, including outer radial glia, which are hypothesized to contribute to human cortical expansion. Our findings support that HARs influenced human brain evolution by altering the expression of conserved gene targets and provide the means to functionally link HARs with novel human brain features., Competing Interests: Competing Interests: The authors declare no competing financial interests.

Colorectal cancer (CRC) is a common malignant tumor and is one of the three most common cancers worldwide. Traditional surgical treatment, supplemented by chemotherapy and radiotherapy, has obvious side effects on patients. Immunotherapy may lead to some unpredictable complications. Low introduction rate and high cost are some of the problems of gene therapy, so finding a safe, reliable and least toxic treatment method became the main research direction for this study. Lactic acid bacteria and their metabolites are widely used in functional foods or as adjuvant therapies for various diseases because they are safe to eat and have no adverse reactions. Research has shown that lactic acid bacteria and their metabolites play an auxiliary therapeutic role in colorectal cancer mainly by improving the intestinal flora composition, inhibiting the growth of pathogenic bacteria and inhibiting the proliferation of cancer cells. It is now widely believed that the substances that probiotics such as lactic acid bacteria exert anti-cancer effects are mainly secondary metabolites such as butyric acid. Lb. plantarum AY01 isolated from fermented food has good anti-cancer ability, and its main anti-cancer substance is 2'-deoxyinosine. Through flow cytometry detection, it was found that Lb. plantarum AY01 can block cell proliferation in the S phase. In addition, Lb. plantarum AY01 culture reduces the sensitivity of mice to colitis-associated CRC induced by azoxymethane (AOM)/dextran sulfate sodium salt (DSS) and exhibits the occurrence and promotion of tumors. According to transcriptome analysis, Lb. plantarum AY01 may induce apoptosis of colorectal cancer cells by activating the p38 MAPK pathway. This experiment provided possibilities for the treatment of CRC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Bladder cancer (BC) is the tenth most common cancer globally, predominantly affecting men. Early detection and treatment are crucial due to high recurrence rates and poor prognosis for advanced stages. Traditional diagnostic methods like cystoscopy and imaging have limitations, leading to the exploration of noninvasive methods such as liquid biopsy. This review highlights the application of biosensors in BC, including electrochemical and optical sensors for detecting tumor markers like proteins, nucleic acids, and other biomolecules, noting their clinical relevance. Emerging therapeutic approaches, such as antibody-drug conjugates, targeted therapy, immunotherapy, and gene therapy, are also explored, the role of biosensors in detecting corresponding biomarkers to guide these treatments is examined. Finally, the review addresses the current challenges and future directions for biosensor applications in BC, highlighting the need for large-scale clinical trials and the integration of advanced technologies like deep learning to enhance diagnostic accuracy and treatment efficacy.

The increasing prevalence of mobility impairments underscores the urgent need for accessible and affordable mobility aids. To overcome the mobility limitations of people with disabilities, there is an increasing need for the development of lightweight and portable powered wheelchairs that can be easily loaded. This study aimed to perform an early health technology assessment and a formative usability evaluation on a modular (detachable) powered wheelchair. It aimed to gauge device satisfaction among users, pinpoint areas for improvement, and detect any unforeseen errors to inform future development. Engaging 16 participants, including powered wheelchair users, healthcare professionals, and caregivers, the research evaluated the wheelchair's functionality in various scenarios, emphasizing safety, effectiveness, and convenience. Statistical analyses of task performance and satisfaction surveys highlighted that, while powered wheelchair users successfully completed tasks focusing on driving and power control, healthcare professionals and caregivers encountered difficulties with the wheelchair's assembly and disassembly. Despite general positivity, the surveys indicated mixed satisfaction levels regarding safety, validity, and convenience, with specific issues related to frame durability, seat comfort, and control mechanisms. These findings suggest that refining the wheelchair's design and addressing user concerns could significantly enhance satisfaction and mobility services. Future efforts will include a thorough review of an advanced prototype and further satisfaction assessments.

The evolution of the human cerebral cortex involved modifications in the composition and proliferative potential of the neural stem cell (NSC) niche during brain development. Human Accelerated Regions (HARs) exhibit a significant excess of human-specific sequence changes and have been implicated in human brain evolution. Multiple studies support that HARs include neurodevelopmental enhancers with novel activities in humans, but their biological functions in NSCs have not been empirically assessed at scale. Here we conducted a direct-capture Perturb-seq screen repressing 180 neurodevelopmentally active HARs in human iPSC-derived NSCs with single-cell transcriptional readout. After profiling >188,000 NSCs, we identified a set of HAR perturbations with convergent transcriptional effects on gene networks involved in NSC apicobasal polarity, a cellular process whose precise regulation is critical to the developmental emergence of basal radial glia (bRG), a progenitor population that is expanded in humans. Across multiple HAR perturbations, we found convergent dysregulation of specific apicobasal polarity and adherens junction regulators, including PARD3, ABI2, SETD2 , and PCM1 . We found that the repression of one candidate from the screen, HAR181, as well as its target gene CADM1 , disrupted apical PARD3 localization and NSC rosette formation. Our findings reveal interconnected roles for HARs in NSC biology and cortical development and link specific HARs to processes implicated in human cortical expansion.

Background: Systemic inflammation is believed to contribute to small cell lung cancer (SCLC) progression, but the underlying relationship remains unclear. Lipocalin-2, a potential biomarker of inflammation, has been implicated in various cancers but its prognostic value in SCLC is underexplored., Methods: We retrospectively analyzed 191 patients with SCLC (72 with limited-stage [LD] and 119 with extensive-stage) treated using platinum-based chemotherapy. Lipocalin-2 expression was evaluated using immunohistochemistry. Optimal cutoff values for lipocalin-2 and neutrophil-to-lymphocyte ratio (NLR) were determined using time-dependent receiver operating characteristic curve analysis. The pectoralis muscle index was used to assess sarcopenia., Results: In LD-SCLC, high lipocalin-2 expression was associated with worse progression-free survival (PFS; median: 7.0 vs. 15.9 months, p = 0.015) and overall survival (OS; median: 12.9 vs. 30.3 months, p = 0.035) compared with low lipocalin-2 expression. Patients were stratified into three prognostic groups by combining lipocalin-2 with NLR: low lipocalin-2/low NLR, high lipocalin-2/low NLR or low lipocalin-2/high NLR, and high lipocalin-2/high NLR (median PFS: 17.3 vs. 11.0 vs. 6.3 months, p = 0.004; median OS: 30.5 vs. 17.3 vs. 8.6 months, p = 0.002). Similar trends were observed when combining lipocalin-2 with the pectoralis muscle index. High lipocalin-2 expression was also associated with lower complete response rates (18.9% vs. 34.3%, p = 0.035). No significant prognostic implications were found for lipocalin-2 in extensive-stage SCLC., Conclusions: High lipocalin-2 expression is potentially associated with poorer survival in LD-SCLC. Combining lipocalin-2 with other inflammation-related markers could improve prognostic stratification., (© 2024 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Microneedle patches have been developed as favorable platforms for delivery systems, such as the locoregional application of therapeutic drugs, and implantation systems, such as electronic devices on visceral tissue surfaces. However, the challenge lies in finding materials that can achieve both biocompatibility and stable fixation on the target tissue. To address this issue, utilizing a biocompatible adhesive biomaterial allows the flat part of the patch to adhere as well, enabling double-sided adhesion for greater versatility. In this work, we propose an adhesive microneedle patch based on mussel adhesive protein (MAP) with enhanced mechanical strength via ultraviolet-induced polyacrylate crosslinking and Coomassie brilliant blue molecules. The strong wet tissue adhesive and biocompatible nature of engineered acrylated-MAP resulted in the development of a versatile wet adhesive microneedle patch system for in vivo usage. In a mouse tumor model, this microneedle patch effectively delivered anticancer drugs while simultaneously sealing the skin wound. Additionally, in an application of rat subcutaneous implantation, an electronic circuit was stably anchored using a double-sided wet adhesive microneedle patch, and its signal location underneath the skin did not change over time. Thus, the proposed acrylated-MAP-based wet adhesive microneedle patch system holds great promise for biomedical applications, paving the way for advancements in drug delivery therapeutics, tissue engineering, and implantable electronic medical devices., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: This study examined the effect of cognitive bias modification for interpretation (CBM-I) training in Korean women with eating disorders (EDs)., Method: Sixty-three women with EDs participated in the study. Participants were randomly assigned to the intervention group where they received six sessions of CBM-I training (n = 31) in addition to treatment-as-usual or were put on a waiting list (n = 32). Participants' interpretation and attention biases, emotion regulation, affect, and ED psychopathology were assessed at baseline, end-of-intervention (4 weeks), and follow-up (8 weeks)., Results: Participants who completed the CBM-I training displayed greater reductions in negative interpretation bias (Δη 2 = 0.107) and emotion dysregulation (Δη 2  = 0.085) with medium to large effect sizes compared to the control group, which were maintained from baseline to follow-up. Disengagement from negative faces and a focus on positive faces was found in the intervention group with a moderate effect size at the end-of-intervention (Δη 2  = 0.090). Both intervention and control groups showed improvements in ED psychopathology. Baseline neuroticism was positively correlated with CBM-I effect., Discussion: The results suggest that modifying interpretation bias towards ambiguous social stimuli might be an effective adjuvant treatment to reduce negative expectations of social situations and improve emotion regulation in women with bulimia nervosa and anorexia nervosa., (© 2024 Eating Disorders Association and John Wiley & Sons Ltd.)

Root-knot nematode (Meloidogyne incognita) causes severe crop damage and large economic losses worldwide. Several cultivars of sweetpotato [Ipomoea batatas (L.) Lam)] have been developed with root-knot nematode-resistant traits; however, many of these cultivars do not have favorable agronomic characteristics. To understand the genetic traits underlying M. incognita resistance in sweetpotato, whole genome resequencing was conducted on three RKN-susceptible (Dahomi, Shinhwangmi, and Yulmi) and three RKN-resistant (Danjami, Pungwonmi, and Juhwangmi) sweetpotato cultivars. Three SNPs (single nucleotide polymorphisms) in promotor sequences were shared in RKN-resistant cultivars and were correlated with disease resistance. One of these SNPs was located in G6617|TU10904, which encoded a homolog of RIBOSOMAL PROTEIN EL15Z, and was associated with reduced expression in RKN-resistant cultivars only. Alongside SNP analysis, mRNA-seq data were analyzed for the same cultivars with and without nematode infection, and 18 nematode-sensitive genes were identified that responded in a cultivar-specific manner. Of these genes, expression of G8735|TU14367 was lower in sensitive cultivars than in RKN-resistant cultivars. Overall, this study identified two genes that potentially have key roles in the regulation of nematode resistance and will be useful targets for nematode resistance breeding programs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Social isolation not only increases the risk of mortality in later life but also causes depressive symptoms, cognitive and physical disabilities. Although RNA m6A modifications are suggested to play key roles in brain development, neuronal signaling and neurological disorders, both the roles of m6A and the enzymes that regulate RNA m6A modification in social isolation induced abnormal behavior is unknown. The present study aims to explore the possible epitranscriptomic role of RNA m6A modifications and its enzymes in social isolation induced impaired behavior., Methods: 3-4 weeks mice experiencing 8 weeks social isolation stress (SI) were used in the present study. We quantified m6A levels in brain regions related to mood and cognitive behavior. And the expression of hippocampal m6A enzymes was also determined. The role of hippocampal m6A and its enzymes in SI induced abnormal behavior was further verified by the virus tool., Results: SI led to not only depressive and anxiety-like behaviors but also cognitive impairment, with corresponding decreases in hippocampal m6A and METTL14. Hippocampal over-expression METTL14 with lentivirus not only rescued these behaviors but also enhanced the hippocampal m6A level. Hippocampal over-expression METTL14 resulted in increased synaptic related genes., Conclusions: We provide the first evidence that post-weaning social isolation reduces hippocampal m6A level and causes altered expression of m6A enzyme in mice. Importantly, hippocampal METTL14 over-expression alleviated the SI-induced depression/anxiety-like and impaired cognitive behaviors and enhanced m6A level and synaptic related genes expression., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest or any known competing financial interests or personal relationships that may bias the performance or interpretation of the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Kidney transplantation (KT) improves physical and psychological prognoses for patients with end-stage kidney disease (ESKD). However, few comparative studies have examined depression and suicide rates among patients with ESKD treated with dialysis versus KT., Methods: Data on 21,809 patients with ESKD were extracted from the Korean National Health Insurance Service database, extending from January 2002 to December 2018. These patients exhibited no history of depression or insomnia before starting renal replacement therapy. Outcomes were compared between dialysis and KT recipients using 1:2 propensity score matching (PSM)., Results: Of the patients, 17,649 received dialysis (hemodialysis, 15,537; peritoneal dialysis, 2,112), while 4,160 underwent KT. Of those on dialysis, 45.04% (7,949) experienced insomnia, compared to 25.72% (1,070) of KT recipients (P<0.001). Depression was more frequent among dialysis recipients (22.77%, 4,019) than KT recipients (8.61%, 358; P<0.001). Additionally, those on dialysis had a higher incidence of suicide (0.19%, 33) than recipients of KT (0.12%, 5; P=0.047). After PSM, the hazard ratio (HR) for depression in patients on dialysis compared to KT recipients was 1.76 (95% confidence interval [CI], 1.56-1.99). In subgroup analysis, the relative likelihood of depression among dialysis recipients was particularly high for residents of urban areas (HR, 2.10; 95% CI, 1.80-2.44) and patients under 65 years old (HR, 1.82; 95% CI, 1.62-2.09)., Conclusions: KT recipients exhibit a lower suicide rate than patients on dialysis. Furthermore, KT is associated with a lower prevalence of depression among Korean patients with ESKD, particularly urban residents and individuals under 65 years old.