Correction: Aggregation or phase separation can be induced in highly charged proteins by small charged biomolecules.

Correction for 'Aggregation or phase separation can be induced in highly charged proteins by small charged biomolecules' by Minchae Kang et al., Soft Matter, 2022, 18, 3313-3317, https://doi.org/10.1039/D2SM00384H.

Polyunsaturated fatty acid biosynthesis pathway determines ferroptosis sensitivity in gastric cancer.

Ferroptosis is an iron-dependent regulated necrosis mediated by lipid peroxidation. Cancer cells survive under metabolic stress conditions by altering lipid metabolism, which may alter their sensitivity to ferroptosis. However, the association between lipid metabolism and ferroptosis is not completely understood. In this study, we found that the expression of elongation of very long-chain fatty acid protein 5 (ELOVL5) and fatty acid desaturase 1 (FADS1) is up-regulated in mesenchymal-type gastric cancer cells (GCs), leading to ferroptosis sensitization. In contrast, these enzymes are silenced by DNA methylation in intestinal-type GCs, rendering cells resistant to ferroptosis. Lipid profiling and isotope tracing analyses revealed that intestinal-type GCs are unable to generate arachidonic acid (AA) and adrenic acid (AdA) from linoleic acid. AA supplementation of intestinal-type GCs restores their sensitivity to ferroptosis. Based on these data, the polyunsaturated fatty acid (PUFA) biosynthesis pathway plays an essential role in ferroptosis; thus, this pathway potentially represents a marker for predicting the efficacy of ferroptosis-mediated cancer therapy.

Structural basis for recognition of the tumor suppressor protein PTPN14 by the oncoprotein E7 of human papillomavirus.

Human papillomaviruses (HPVs) are causative agents of various diseases associated with cellular hyperproliferation, including cervical cancer, one of the most prevalent tumors in women. E7 is one of the two HPV-encoded oncoproteins and directs recruitment and subsequent degradation of tumor-suppressive proteins such as retinoblastoma protein (pRb) via its LxCxE motif. E7 also triggers tumorigenesis in a pRb-independent pathway through its C-terminal domain, which has yet been largely undetermined, with a lack of structural information in a complex form with a host protein. Herein, we present the crystal structure of the E7 C-terminal domain of HPV18 belonging to the high-risk HPV genotypes bound to the catalytic domain of human nonreceptor-type protein tyrosine phosphatase 14 (PTPN14). They interact directly and potently with each other, with a dissociation constant of 18.2 nM. Ensuing structural analysis revealed the molecular basis of the PTPN14-binding specificity of E7 over other protein tyrosine phosphatases and also led to the identification of PTPN21 as a direct interacting partner of E7. Disruption of HPV18 E7 binding to PTPN14 by structure-based mutagenesis impaired E7's ability to promote keratinocyte proliferation and migration. Likewise, E7 binding-defective PTPN14 was resistant for degradation via proteasome, and it was much more effective than wild-type PTPN14 in attenuating the activity of downstream effectors of Hippo signaling and negatively regulating cell proliferation, migration, and invasion when examined in HPV18-positive HeLa cells. These results therefore demonstrated the significance and therapeutic potential of the intermolecular interaction between HPV E7 and host PTPN14 in HPV-mediated cell transformation and tumorigenesis.

Aggregation or phase separation can be induced in highly charged proteins by small charged biomolecules.

Protein phase separation in biological systems has captured the attention of scientists in the last decade; however, the main mechanism underlying protein phase separation in cells remains unclear. Biologists, physicists, and chemists have all tried to understand this important biological phenomenon, each using their own unique techniques and language. Each subject has its advantages in explaining protein phase separation; however, in this study, we find that the chemical language of molecular structure is the key to explaining the mechanism underlying protein phase separation. Using fluroescence microscopy and molecular dynamics, this study identifies small multivalently charged biomolecules, such as nucleoside triphosphate (negatively charged) and polyamine (positively charged), as important drivers of phase separation of highly charged proteins in cells.

Analysis and Guidelines for Revisional Malarplasty; Most Common Facial Skeletal Contouring Surgery.

BACKGROUND: Revisional malarplasty is the most frequently performed and difficult to perform revision surgery among facial contouring surgeries. The incidence of postoperative complications and need for revision surgery is increasing because of indiscriminate malar reduction through a narrow surgical space. The authors analyzed cases of revisional malarplasty secondary to complications. METHODS: The authors analyzed the time required and technique used in 172 patients who underwent revisional malarplasty in the past 3 years. The incision made for the approach and the graft material used for reconstruction were also investigated. RESULTS: Of 172 patients, 35 (20.3%) underwent emergency revision. Furthermore, 71 (41.2%) required an intraoral incision, and 101 (58.8%) required a coronal incision. A total of 81(47.1%) patients required artificial or autogenous bone grafts. CONCLUSIONS: Patients with failed malarplasty should receive immediate intervention to prevent functional and cosmetic problems. When bone resorption occurs due to unfavorable union or nonunion, reconstruction using appropriate autologous tissue can prevent functional impairment and long-term cosmetic problems.

Safety and efficacy of letibotulinumtoxinA(BOTULAX®) in treatment of post stroke upper limb spasticity: a randomized, double blind, multi-center, phase III clinical trial.

OBJECTIVE: To investigate a new botulinum neurotoxin type A, termed letibotulinumtoxinA(Botulax®) and compare its efficacy and safety for post-stroke upper limb spasticity with that of onabotulinumtoxinA(Botox®). DESIGN: A prospective, double-blinded, multicenter, randomized controlled clinical study. SETTING: Six university hospitals in Korea. SUBJECTS: A total of 187 stroke participants with upper limb spasticity. INTERVENTIONS: Two kinds of botulinum neurotoxin type A were used. One set of injection was performed and total injected doses were 309.21±62.48U(Botulax) and 312.64±49.99U(Botox)( P>0.05). MAIN MEASURES: Primary outcome was measured using the modified Ashworth scale for wrist flexors at week 4 and secondary outcome was measured using modified Ashworth scale for wrist flexors, elbow flexors, finger flexors, and thumb flexors as well as Global Assessment in spasticity, Disability Assessment Scale, and Caregiver Burden Scale. Safety measures including adverse events, vital signs and physical examination, and laboratory tests were also monitored. RESULTS: The mean ages for the Botulax group were 56.81±9.49 and which for the Botox group were 56.93±11.93( P>0.05). In primary outcome, the change in modified Ashworth scale for wrist flexors was -1.45±0.61 in the Botulax group and -1.40±0.57 in the Botox group, and the difference between the two groups was -0.06(95% CI:-0.23-0.12, P>0.05). In secondary outcome, both groups demonstrated significant improvements with respect to modified Ashworth scale, Global Assessment in spasticity, Disability Assessment Scale, and Caregiver Burden Scale ( P<0.05), and no significant difference was observed between the two groups ( P>0.05). In addition, safety measures showed no significant differences between the two groups ( P>0.05). CONCLUSIONS: The efficacy and safety of Botulax were comparable with those of Botox in treatment of post-stoke upper limb spasticity.

Language-specific dysgraphia in Korean patients with right brain stroke: influence of unilateral spatial neglect.

The purpose of the present study was to investigate the relationship between Korean language-specific dysgraphia and unilateral spatial neglect in 31 right brain stroke patients. All patients were tested for writing errors in spontaneous writing, dictation, and copying tests. The dysgraphia was classified into visuospatial omission, visuospatial destruction, syllabic tilting, stroke omission, stroke addition, and stroke tilting. Twenty-three (77.4%) of the 31 patients made dysgraphia and 18 (58.1%) demonstrated unilateral spatial neglect. The visuospatial omission was the most common dysgraphia followed by stroke addition and omission errors. The highest number of errors was made in the copying and the least was in the spontaneous writing test. Patients with unilateral spatial neglect made a significantly higher number of dysgraphia in the copying test than those without. We identified specific dysgraphia features such as a right side space omission and a vertical stroke addition in Korean right brain stroke patients. In conclusion, unilateral spatial neglect influences copy writing system of Korean language in patients with right brain stroke.

Nuclear localization of huntingtin during spermatogenesis.

Huntingtin is a ubiquitous cytoplasmic protein. Mutant huntingtin causes Huntington's disease and its intranuclear inclusion is associated with cytotoxicity. Nuclear localization of normal huntingtin is detected in the oocyte up to 2.5 days post coitum. Therefore, huntingtin is expected to reside in the nucleus even before fertilization. The present study determined normal huntingtin distribution during spermatogenesis. Testicles from an adult male Sprague-Dawley rat were stained with anti-huntingtin antibody and nuclear counterstaining was performed with 4',6-diamidino-2-phenylindole. Concerning nuclear localization, huntingtin was detected in the spermatids, whereas predominant cytoplasmic localization of it was evident in the spermatogonia. Between the primary and secondary spermatocytes, huntingtin appeared to be delocalized in the nuclei when meiosis occurred. The findings provide evidence that normal huntingtin is transported to the nuclear compartment during the meiotic stage of spermatogenesis.

Correlating ultrasound findings of carpal tunnel syndrome with nerve conduction studies.

INTRODUCTION: The aim of this study was to make correlations between ultrasonographic measurements of thenar muscle and flexor retinaculum and nerve conduction studies (NCS) in carpal tunnel syndrome (CTS). METHODS: Ultrasound and NCS were performed on 92 wrists with CTS and on 40 wrists from healthy individuals. Ultrasound of thenar and hypothenar muscles, flexor retinaculum, and median nerve were assessed. The ultrasonographic findings were compared between the 2 groups, and correlation analyses between median latency and ultrasonographic findings were performed. RESULTS: Motor latency correlated positively with flexor retinaculum thickness (FRT) and negatively with the ratio of thenar to hypothenar muscle. FRT and motor latency were found to be increased significantly in CTS. The ratio of thenar to hypothenar muscle was found to be decreased significantly in CTS compared with controls. CONCLUSIONS: The ultrasonographic findings of FRT and thenar muscle reflect the severity of disease in patients with CTS and are valuable for the diagnosis of CTS.

Phosphorylation of OTUB1 at Tyr 26 stabilizes the mTORC1 component, Raptor.

Raptor plays a critical role in mTORC1 signaling. High expression of Raptor is associated with resistance of cancer cells to PI3K/mTOR inhibitors. Here, we found that OTUB1-stabilized Raptor in a non-canonical manner. Using biochemical assays, we found that the tyrosine 26 residue (Y26) of OTUB1 played a critical role in the interaction between OTUB1 and Raptor. Furthermore, non-receptor tyrosine kinases (Src and SRMS kinases) induced phosphorylation of OTUB1 at Y26, which stabilized Raptor. Interestingly, phosphorylation of OTUB1 at Y26 did not affect the stability of other OTUB1-targeted substrates. However, dephosphorylation of OTUB1 destabilized Raptor and sensitized cancer cells to anti-cancer drugs via mitochondrial reactive oxygen species-mediated mitochondrial dysfunction. Furthermore, we detected high levels of phospho-OTUB1 and Raptor in samples of patients with renal clear carcinoma. Our results suggested that regulation of OTUB1 phosphorylation may be an effective and selective therapeutic target for treating cancers via down-regulation of Raptor.

The lipoprotein-associated phospholipase A2 inhibitor Darapladib sensitises cancer cells to ferroptosis by remodelling lipid metabolism.

Arachidonic and adrenic acids in the membrane play key roles in ferroptosis. Here, we reveal that lipoprotein-associated phospholipase A2 (Lp-PLA2) controls intracellular phospholipid metabolism and contributes to ferroptosis resistance. A metabolic drug screen reveals that darapladib, an inhibitor of Lp-PLA2, synergistically induces ferroptosis in the presence of GPX4 inhibitors. We show that darapladib is able to enhance ferroptosis under lipoprotein-deficient or serum-free conditions. Furthermore, we find that Lp-PLA2 is located in the membrane and cytoplasm and suppresses ferroptosis, suggesting a critical role for intracellular Lp-PLA2. Lipidomic analyses show that darapladib treatment or deletion of PLA2G7, which encodes Lp-PLA2, generally enriches phosphatidylethanolamine species and reduces lysophosphatidylethanolamine species. Moreover, combination treatment of darapladib with the GPX4 inhibitor PACMA31 efficiently inhibits tumour growth in a xenograft model. Our study suggests that inhibition of Lp-PLA2 is a potential therapeutic strategy to enhance ferroptosis in cancer treatment.

Clinical Practice Guidelines for Oropharyngeal Dysphagia.

OBJECTIVE: Dysphagia is a common clinical condition characterized by difficulty in swallowing. It is sub-classified into oropharyngeal dysphagia, which refers to problems in the mouth and pharynx, and esophageal dysphagia, which refers to problems in the esophageal body and esophagogastric junction. Dysphagia can have a significant negative impact one's physical health and quality of life as its severity increases. Therefore, proper assessment and management of dysphagia are critical for improving swallowing function and preventing complications. Thus a guideline was developed to provide evidence-based recommendations for assessment and management in patients with dysphagia. METHODS: Nineteen key questions on dysphagia were developed. These questions dealt with various aspects of problems related to dysphagia, including assessment, management, and complications. A literature search for relevant articles was conducted using Pubmed, Embase, the Cochrane Library, and one domestic database of KoreaMed, until April 2021. The level of evidence and recommendation grade were established according to the Grading of Recommendation Assessment, Development and Evaluation methodology. RESULTS: Early screening and assessment of videofluoroscopic swallowing were recommended for assessing the presence of dysphagia. Therapeutic methods, such as tongue and pharyngeal muscle strengthening exercises and neuromuscular electrical stimulation with swallowing therapy, were effective in improving swallowing function and quality of life in patients with dysphagia. Nutritional intervention and an oral care program were also recommended. CONCLUSION: This guideline presents recommendations for the assessment and management of patients with oropharyngeal dysphagia, including rehabilitative strategies.

Clinical Practice Guideline for Stroke Rehabilitation in Korea-Part 1: Rehabilitation for Motor Function (2022).

This clinical practice guideline (CPG) is the fourth edition of the Korean guideline for stroke rehabilitation, which was last updated in 2016. The development approach has been changed from a consensus-based approach to an evidence-based approach using the Grading of Recommendations Assessment Development and Evaluation (GRADE) method. This change ensures that the guidelines are based on the latest and strongest evidence available. The aim is to provide the most accurate and effective guidance to stroke rehabilitation teams, and to improve the outcomes for stroke patients in Korea. Fifty-five specialists in stroke rehabilitation and one CPG development methodology expert participated in this development. The scope of the previous clinical guidelines was very extensive, making it difficult to revise at once. Therefore, it was decided that the scope of this revised CPG would be limited to Part 1: Rehabilitation for Motor Function. The key questions were selected by considering the preferences of the target population and referring to foreign guidelines for stroke rehabilitation, and the recommendations were completed through systematic literature review and the GRADE method. The draft recommendations, which were agreed upon through an official consensus process, were refined after evaluation by a public hearing and external expert evaluation.

A Pilot Study for the Neuroprotective Effect of Gongjin-dan on Transient Middle Cerebral Artery Occlusion-Induced Ischemic Rat Brain.

In this study, we investigated whether gongjin-dan improves functional recovery and has neuroprotective effects on reducing the infarct volume after transient middle cerebral artery occlusion (MCAo). Infarct volume was measured using TTC staining and glucose utilization by F-18 FDG PET. Functional improvement was evaluated with the Rota-rod, treadmill, Garcia score test, and adhesive removal test. At 14 days after MCAo, neuronal cell survival, astrocytes expansion, and apoptosis were assessed by immunohistofluorescence staining in the peri-infarct region. Also, the expression of neurotrophic factors and inflammatory cytokines such as VEGF, BDNF, Cox-2, TNF-α, IL-1ß, and IL-1α was measured in ischemic hemisphere regions. The gongjin-dan-treated group showed both reduced infarct volume and increased glucose utilization. Behavior tests demonstrated a significant improvement compared to the control. Also in the gongjin-dan treated group, NeuN-positive cells were increased and number of astrocytes, microglia, and apoptotic cells was significantly decreased compared with the control group in the ischemic peri-infarct area. Furthermore, the expression of VEGF and BDNF was increased and level of Cox-2, TNF-α, IL-1ß, and IL-1α was decreased. These results suggest that gongjin-dan may improve functional outcome through the rapid restoration of metabolism and can be considered as a potential neuroprotective agent.

Korean Brain Rehabilitation Registry for rehabilitation of persons with brain disorders: annual report in 2009.

This first annual report provides a description of patients discharged from rehabilitation facilities in Korea based on secondary data analysis of Korean Brain Rehabilitation Registry V1.0 subscribed in 2009. The analysis included 1,697 records of patients with brain disorders including stroke, traumatic brain injury, brain tumor and other disorders from 24 rehabilitation facilities across Korea. The data comprised 1,380 cases of stroke, 104 cases of brain injury, 55 cases of brain tumor, and 58 cases of other brain diseases. The functional status of each patient was measured using the Korean version of the Modified Barthel Index (KMBI). The average change in the KMBI score was 15.9 for all patients in the inpatient rehabilitation facility. The average length of stay for inpatient rehabilitation was 36.9 days. The transfer rates to other hospitals were high, being 62.4% when all patients were considered. Patients with brain disorders of Korea in 2009 and measurable functional improvement was observed in patients. However, relatively high percentages of patients were not discharged to the community after inpatient rehabilitation. Based on the results of this study, consecutive reports of the status of rehabilitation need to be conducted in order to provide useful information to many practitioners.

Correlation of Body Composition via Bioelectrical Impedance Analysis and Motor Function and Recovery of Upper Extremity in Patients Undergoing Stroke Rehabilitation.

Bioelectrical impedance analysis (BIA) has been used to investigate the body compositions and predict functional outcomes in patients with stroke, while the role of BIA to predict motor function or recovery in stroke has not been clarified. This study aimed to investigate relationship between body composition measured by BIA and upper limb motor function and recovery. Body compositions (soft tissue lean mass, phase angle, body fat mass and body water) of fifty patients who are admitted to the stroke rehabilitation unit were segmentally analyzed via BIA. The motor recovery of upper extremity (UE) was evaluated via Fugl-Meyer Assessment (UE-FMA) at the time of transfer and discharge. Correlations between body composition and UE-FMA at discharge were analyzed using Spearman correlation coefficient. Multiple regression analysis was used to determine the regression between body composition and motor function and recovery. The Δ Phase angle, the difference of both sides was significantly linearly inversely correlated with UE-FMA at discharge. However, in multiple regression analysis, body compositions including phase angle did not significantly predict motor function at discharge or motor recovery. The Δ Phase angle is related to the severity of upper limb motor function at discharge in subacute stroke patients, and further studies are needed to determine its value as a predictor for motor recovery.

Reconstruction of temporal hollowing deformities using silicone implants made using a toy-clay model: a report of three cases.

Severe temporal hollowing deformities can occur in patients who undergo craniectomy after intracranial hemorrhage. Reconstruction surgery for cosmetic purposes using silicone implants in patients with temporal hollowing deformities after craniectomy is advantageous because the procedure is simple and rapid, with a short recovery time, resulting in lower overall treatment costs. Of paramount importance, this option yields highly satisfactory results for patients. The authors present three cases of simple and fast surgery using silicone implants where highly satisfactory outcomes were obtained.

Motor-evoked potential confirmation of functional improvement by transplanted bone marrow mesenchymal stem cell in the ischemic rat brain.

This study investigated the effect of bone marrow mesenchymal stem cells (BMSCs) on the motor pathway in the transient ischemic rat brain that were transplanted through the carotid artery, measuring motor-evoked potential (MEP) in the four limbs muscle and the atlantooccipital membrane, which was elicited after monopolar and bipolar transcortical stimulation. After monopolar stimulation, the latency of MEP was significantly prolonged, and the amplitude was less reduced in the BMSC group in comparison with the control group (P < .05). MEPs induced by bipolar stimulation in the left forelimb could be measured in 40% of the BMSC group and the I wave that was not detected in the control group was also detected in 40% of the BMSC group. Our preliminary results imply that BMSCs transplanted to the ischemic rat brain mediate effects on the functional recovery of the cerebral motor cortex and the motor pathway.

The effects of additional electrical stimulation combined with repetitive transcranial magnetic stimulation and motor imagery on upper extremity motor recovery in the subacute period after stroke: A preliminary study.

BACKGROUND: To evaluate the therapeutic effects of additional electrical stimulation (ES) combined with low frequency (LF)-repetitive transcranial magnetic stimulation (rTMS) and motor imagery (MI) training on upper extremity (UE) motor function following stroke. METHODS: The participants with subacute stroke in the experimental group (n = 8) received LF rTMS + MI + active ES interventions, and those in control group (n = 9) received LF rTMS + MI + sham ES interventions. Interventions were performed 5 days a week for 2 weeks, for a total of 10 sessions. All participants were given the same dosage of conventional rehabilitation during the study period. The primary outcome measure was the UE Fugl-Meyer Assessment (FMA). The secondary outcome measures were the shoulder abduction and finger extension scores, modified Barthel Index, Purdue Pegboard Test, and finger tapping test. All scores were measured before and just after the intervention. RESULTS: After the 2-week intervention period, the FMA and modified Barthel Index scores were improved in both groups compared to baseline assessment (P < .001 in the experimental group and P = .008 in the control group). Of note, the change in FMA scores was significantly higher in the experimental group compared with that of the control group (P = .04). CONCLUSION: These results suggest that the use of LF rTMS + MI combined with additional ES lead to greater improvement of UE motor function after stroke. As such, this intervention may be a promising adjuvant therapy in UE motor training.

Concurrence of Congenital Muscular Torticollis and Congenital Torticollis Due to Other Anomalies: Two Case Reports.

Introduction: Congenital muscular torticollis (CMT) is the most common cause of torticollis in infants; other causes, including osseous, ocular, and central nervous system torticollis can easily be overlooked. We report two rare cases of CMT with concurrent osseous or ocular torticollis. Case 1: A 1-month-old female infant with a right neck mass and right-tilting head posture was referred. Neck ultrasonography showed diffuse hypertrophy and hyperechoic findings on the right sternocleidomastoid (SCM) muscle, which was consistent with right CMT. A clavicle X-ray imaging was conducted to identify an associated fracture due to birth trauma on the same day and a suspected congenital vertebral anomaly was coincidentally found. Subsequent three-dimensional computed tomography of the cervical spine showed a T1 hemivertebra causing the right-tilting head. The patient was diagnosed with the concurrent manifestation of CMT and congenital osseous torticollis. Case 2: A 3-month-old male infant with a 20° head tilt to the right with a limited cervical range of motion was referred. Neck ultrasonography showed a fibromatosis colli in the right SCM, suggesting CMT. He proceeded to physical therapy for seven months; however, there was little clinical improvement in his head and neck posture. The patient underwent an additional ophthalmologic examination and orbital magnetic resonance imaging (MRI) at 10 months of age. The result showed congenital agenesis of the left fourth cranial nerve with hypoplasia of the superior oblique muscle causing the right-tilting of the head. Ultimately, the boy was diagnosed with a concurrent manifestation of CMT and congenital ocular torticollis. Conclusion: Unless careful examinations are conducted, congenital vertebral anomalies and congenital agenesis of the fourth cranial nerve can go unnoticed in the present two cases. If a patient with CMT displays unusual features or does not respond to physical therapy, clinicians should consider not only a differential diagnosis but also concurrence with other causes of congenital torticollis.