bluuebunny/crossref_metadata_2025_split huggingface dataset:
FN3 Domain Displaying Double Epitopes: A Cost-Effective Strategy for Producing Substitute Antigens
Authors: Ruan Yao , Chao Shuangying , Hu Xuejun , Lu Longzhen , Lin Yue , Wang Qian , Zheng Yang , Li Junming , Ding Ning 
Published: November 2021

Construction of substitute antigens based on alternative scaffold proteins is a promising strategy in bioassay technology. In this study, we proposed a strategy for constructing substitute antigens derived from 10th human fibronectin type III (FN3) using two peptide epitopes of terminal pro-brain natriuretic peptide (NT-proBNP) as an example. The base sequences encoding the two antigenic epitopes of NT-proBNP were recombined into the FG loop region and the C-terminus of FN3, fused by 4 GS or polyN linker. The fusion proteins (named FN3-epitopes-4GS and FN3-epitopes-polyN, respectively) were expressed and purified cost-effectively using an Escherichia coli expression system. The immunoreactivity of recombinant substitutes was preliminarily confirmed by western blot analysis using epitope-specific antibodies. The sandwich enzyme-linked immunosorbent assay demonstrated that either FN3-epitopes-polyN or FN3-epitopes-4GS was highly sensitive, and FN3-epitopes-polyN exhibited better kinetics to specific antibodies than FN3-epitopes-4GS, showing a linear dose-response relationship in the concentration range of 0.06–12.85 ng/ml, which suggest that the polyN linker was more suitable for constructing the FN3-based substitute antigens compared to the 4 GS linker. Furthermore, the serum stability test and differential scanning calorimetry analysis showed that the recombinant FN3-epitopes-polyN maintained the original stability of FN3. Therefore, it was confirmed that FN3 could be engineered to construct a stable biomacromolecular substitute for displaying double epitopes of antigen proteins, such as NT-proBNP. In summary, a cost-effective strategy to produce NT-proBNP substitute antigens with good immunoreactivity and physicochemical stability was established in this work, which may provide potential uses for the production of other substitute antigens in the future.
The Effect of a Combined Ganciclovir, Methylprednisolone, and Immunoglobulin Regimen on Survival and Functional Outcomes in Patients With Japanese Encephalitis
Authors: Miao Wang , Guo Junshuang , Zhang Shuyu , Shen Nannan , Shang Xiaoping , Liu Furong , Lu Warren , Xu Jianghai , Teng Junfang 
Published: November 2021

Objective: There is currently no effective treatment for Japanese encephalitis, which has a high rate of morbidity and mortality. This study assessed the effectiveness of a ganciclovir, methylprednisolone, and immunoglobulin combination (TAGMIC) therapy in decreasing cognitive impairment and mortality among patients with Japanese encephalitis.Methods: We retrospectively assessed the clinical data of 31 patients diagnosed with Japanese encephalitis, who were admitted to an intensive care unit. Patients were divided into the TAGMIC and non-TAGMIC group according to their treatment regime. We compared the 60-day, 6-month, and overall mortality and survival curves between groups. We also compared Barthel Index scores, Montreal Cognitive Assessment (MoCA) scores, and diffusion tensor imaging (DTI) results.Results: There was no significant difference in the 30-day mortality rate or Kaplan–Meier survival curve between groups. The 60-day, 6-month, and overall mortality rates in the TAGMIC group were significantly reduced (P = 0.043, P = 0.018, and P = 0.018, respectively) compared with the non-TAGMIC group (0, 0, 0 vs. 31.25, 37.5, 37.5%, respectively). The 60-day, 6-month, and overall Kaplan–Meier survival curves were significantly different between groups (P = 0.020, P = 0.009, P = 0.009, respectively). There was no significant difference in the Barthel Index scores of surviving patients. Among the five patients who underwent MoCA and DTI, four had a score of 0/5 for delayed recall (no cue), while the remaining patient had a score of 2/5. All five patients were able to achieve a score of 5/5 with classification and multiple-choice prompts, and had sparse or broken corpus callosum (or other) fibre bundles.Conclusion: TAGMIC treatment can reduce mortality due to severe Japanese encephalitis. The memory loss of surviving patients is mainly due to a disorder of the memory retrieval process, which may be related to the breakage of related fibre bundles.
The Onset of Interictal Spike-Related Ripples Facilitates Detection of the Epileptogenic Zone
Authors: Numata-Uematsu Yurika , Uematsu Mitsugu , Sakuraba Rie , Iwasaki Masaki , Osawa Shinichiro , Jin Kazutaka , Nakasato Nobukazu , Kure Shigeo 
Published: November 2021

Objective: Accurate estimation of the epileptogenic zone (EZ) is essential for favorable outcomes in epilepsy surgery. Conventional ictal electrocorticography (ECoG) onset is generally used to detect the EZ but is insufficient in achieving seizure-free outcomes. By contrast, high-frequency oscillations (HFOs) could be useful markers of the EZ. Hence, we aimed to detect the EZ using interictal spikes and investigated whether the onset area of interictal spike-related HFOs was within the EZ.Methods: The EZ is considered to be included in the resection area among patients with seizure-free outcomes after surgery. Using a complex demodulation technique, we developed a method to determine the onset channels of interictal spike-related ripples (HFOs of 80–200 Hz) and investigated whether they are within the resection area.Results: We retrospectively examined 12 serial patients who achieved seizure-free status after focal resection surgery. Using the method that we developed, we determined the onset channels of interictal spike-related ripples and found that for all 12 patients, they were among the resection channels. The onset frequencies of ripples were in the range of 80–150 Hz. However, the ictal onset channels (evaluated based on ictal ECoG patterns) and ripple onset channels coincided in only 3 of 12 patients.Conclusions: Determining the onset area of interictal spike-related ripples could facilitate EZ estimation. This simple method that utilizes interictal ECoG may aid in preoperative evaluation and improve epilepsy surgery outcomes.
The Role of Continuous Theta Burst TMS in the Neurorehabilitation of Subacute Stroke Patients: A Placebo-Controlled Study
Authors: Dionísio Ana , Gouveia Rita , Castelhano João , Duarte Isabel Catarina , Santo Gustavo C. , Sargento-Freitas João , Duecker Felix , Castelo-Branco Miguel 
Published: November 2021

Objectives: Transcranial magnetic stimulation, in particular continuous theta burst (cTBS), has been proposed for stroke rehabilitation, based on the concept that inhibition of the healthy hemisphere helps promote the recovery of the lesioned one. We aimed to study its effects on cortical excitability, oscillatory patterns, and motor function, the main aim being to identify potentially beneficial neurophysiological effects.Materials and Methods: We applied randomized real or placebo stimulation over the unaffected primary motor cortex of 10 subacute (7 ± 3 days) post-stroke patients. Neurophysiological measurements were performed using electroencephalography and electromyography. Motor function was assessed with the Wolf Motor Function Test. We performed a repeated measure study with the recordings taken pre-, post-cTBS, and at 3 months' follow-up.Results: We investigated changes in motor rhythms during arm elevation and thumb opposition tasks and found significant changes in beta power of the affected thumb's opposition, specifically after real cTBS. Our results are consistent with an excitatory response (increase in event-related desynchronization) in the sensorimotor cortical areas of the affected hemisphere, after stimulation. Neither peak-to-peak amplitude of motor-evoked potentials nor motor performance were significantly altered.Conclusions: Consistently with the theoretical prediction, this contralateral inhibitory stimulation paradigm changes neurophysiology, leading to a significant excitatory impact on the cortical oscillatory patterns of the contralateral hemisphere. These proof-of-concept results provide evidence for the potential role of continuous TBS in the neurorehabilitation of post-stroke patients. We suggest that these changes in ERS/ERD patterns should be further explored in future phase IIb/phase III clinical trials, in larger samples of poststroke patients.
Cochlear Implants in Single-Sided Deafness. Comparison Between Children and Adult Populations With Post-lingually Acquired Severe to Profound Hearing Loss
Authors: Falcón Benítez Nadia , Falcón González Juan Carlos , Ramos Macías Ángel , Borkoski Barreiro Silvia , Ramos de Miguel Ángel 
Published: November 2021

Objective: To determine audiological and clinical results of cochlear implantation (CI) comparing two populations with single-sided deafness (SSD): post-lingually deaf children between 6 and 12 years of age, and post-lingually deaf adults, in order to evaluate the effect of CI in different age groups.Design: Retrospective case review.Setting: Tertiary clinic.Patients and Method: Twenty-three children and twenty-one adult patients that were candidates for CI with single-side deafness were included. In all cases we evaluate: Speech perception thresholds; disyllabic words test (65 dB SPL) were performed in the modalities S0–SCI–SNH and Auditory Lateralization Test. The Speech, Spatial, and Qualities of Hearing Scale (SSQ) questionnaire was also used. All results were obtained after 12 months of CI activation.Results: In children, the most common etiology was idiopathic sensory-neural hearing loss. They showed positive results in the Auditory Lateralization Test. In the Speech Test, word recognition in noise improved from 2% preoperatively to 61.1% at a mean follow-up of 1 year (S0 condition) in children [test with signal in CI side 60% and signal normal hearing side (plugged) 31%]. The processor was used for &gt;12 h in all cases. With respect to the SSQ questionnaire, parents were more satisfied within the postoperative period than within the preoperative period. For adults, the most common etiology was idiopathic sudden sensorineural hearing loss (SNHL). Positive results in the Auditory Lateralization Test were found. With respect to the Speech Test in quiet conditions: Word recognition in noise improved from 5.7% preoperatively to 71.8% at a mean follow-up of 1 year [test with signal in CI side 68% and signal normal hearing side (plugged) 41%]. The processor was used for &gt;12 h. In the SSQ questionnaire, the post-operative results showed a beneficial effect of the CI. No adverse events were reported during the study period. No differences were found between children and adults in all tests in this study.Conclusions: Cochlear implantation in post-lingually deaf adults and children with SSD can achieve a speech perception outcome comparable with CI in conventional candidates. Improvements in spatial hearing were also observed. Careful patient selection and counseling regarding potential benefits are important to optimize outcomes.
Case Report: Kampo Medicine for Non-tuberculous Mycobacterium Pulmonary Disease
Authors: Suzuki Tomoko , Uneda Kazushi , Aoyagi Ryutaro , Kobayashi Takehito , Mitsuma Tadamichi , Nakamoto Hidetomo 
Published: November 2021

Background: While the number of pulmonary tuberculosis cases has decreased, increase in non-tuberculous mycobacterium pulmonary disease (NTM-PD) is a global problem. Guideline-based therapy for NTM-PD sometimes causes complications that prevent treatment completion, and there are many cases of relapse even if the treatment can be completed. In addition to antibacterial treatment, care of host risk factors, such as aging, lean physique and immunosuppressive state, is also very important for the management of NTM-PD. In Japan, Kampo medicine, a traditional Japanese herbal formulation, used alone or in combination with standard multidrug therapy for NTM-PD, has been found to be effective for such cases.Case Presentation: A 77-year-old lean woman had been diagnosed with Mycobacterium intracellulare pulmonary infection 6 years earlier, and had received the standard multidrug treatment 5 years later at a former hospital due to worsening of her symptoms of cough, breathlessness and hemoptysis. However, the treatment was discontinued within a year due to the development of adverse events. She refused the guideline-based antibacterial treatment, and asked for Kampo medicine instead. Bukuryoshigyakuto was subsequently prescribed, which led to cough and sputum, especially hemosputum, being well controlled. With 3 years of Kampo medicine treatment, she gained weight and her hemosputum disappeared. High-resolution computed tomography images showed improvement in her lung condition, and her sputum smear culture was negative for acid-fast bacillus.Conclusion: Various kinds of Kampo medicines have been used empirically for NTM-PD in Japan. A literature review from 1992 to 2020 showed that hozais, in particular, seem to be key drugs for the treatment of host NTM-PD risk factors. Kampo medicines can contribute to comprehensive treatment for NTM-PD management that does not rely solely on antibacterial drugs.
Nomogram for Predicting the Prognoses of Patients With Pancreatic Head Cancer After Pancreaticoduodenectomy: A Population-Based Study on SEER Data
Authors: Zhang Wei , Xu Lin , Che Xu 
Published: November 2021

ObjectiveIn this study, we retrieved the data available in the Surveillance, Epidemiology, and End Results database to identify the prognostic factors for patients with pancreatic head cancer who had undergone pancreaticoduodenectomy and developed a prediction model for clinical reference.MethodsWe screened the data between 1973 and 2015. Propensity score matching (PSM) was used to control for the confounding factors. Kaplan-Meier (log-rank test) curves were used to compare the survival rates. A nomogram was established using multifactorial Cox regression.ResultsIn total, 4099 patients were identified. Their median survival was 22 months, with 74.2%, 36.5%, and 26.2% survival after 1, 3, and 5 years, respectively. The median cancer-specific survival was 24.0 months, with 71.1%, 32.6%, and 21.9% survival after 1, 3, and 5 years, respectively. The results of the Cox proportional risk regression showed that age, insurance status, gender, histological type, degree of tissue differentiation, T and N stages, tumor size, extent of regional lymph node dissection, and postoperative radiotherapy or chemotherapy are independent factors affecting prognosis. PSM was used twice to eliminate any bias from the unbalanced covariates in the raw data. After PSM, the patients who had received postoperative radiotherapy were found to have a better survival prognosis and disease-specific survival prognosis than those who had not received radiotherapy [HR = 0.809, 95% CI (0.731–0.894), P &lt; 0.001 and HR = 0.814, 95% CI (0.732–0.904), P &lt; 0.001; respectively]. A similar result was observed for the patients who had received postoperative chemotherapy versus those who had not [HR = 0.703, 95% CI (0.633–0.78), P &lt; 0.001 and HR = 0.736, 95% CI (0.658–0.822), P &lt; 0.001, for survival and disease-specific survival prognoses, respectively]. Finally, the β coefficients of the Cox proportional risk regression were used to establish a nomogram.ConclusionAge, insurance status, gender, histological type, degree of differentiation, T and N stages, tumor size, regional lymph node dissection, and postoperative radiotherapy or chemotherapy are factors affecting the prognosis in pancreatic head cancer after pancreaticoduodenectomy. Postoperative radiotherapy and chemotherapy can improve patient survival. These still need to be further validated in the future.
Is There a Neuropathic-Like Component to Endometriosis-Associated Pain? Results From a Large Cohort Questionnaire Study
Authors: Coxon Lydia , Wiech Katja , Vincent Katy 
Published: November 2021

Background: Pain is one of the primary symptoms of endometriosis, a chronic inflammatory condition characterised by the presence of endometrial tissue outside the uterus. Endometriosis-associated pain is commonly considered as nociceptive in nature, but its clinical presentation suggests that it might have neuropathic-like properties in a subgroup of patients.Methods: This is a cross sectional study using an online survey. The survey was distributed by patient support websites. The survey was composed of validated questionnaires assessing pain symptoms, psychological measures and questions about number of surgeries.Main Results: We had 1,417 responses which met the inclusion criteria. Using standard painDETECT cut-off scores, we found that pain was classified as neuropathic in 40% of patients and as mixed neuropathic/nociceptive in a further 35%. In line with observations in other neuropathic conditions, the neuropathic subgroup reported higher pain intensities, greater psychological distress and cognitive impairment. Neuropathic pain was also more likely in those with more surgeries to the abdomen and a longer history of pain. As revealed by a cluster analysis, those with a neuropathic pain component could further be divided into two subgroups based on their sensory profile.Conclusions: The data presented here indicate that endometriosis-associated pain includes a neuropathic-like component in a substantial proportion of women. Although further investigation is required, our finding challenges the current conceptualisation of endometriosis-associated pain as nociceptive and advocates for a new perspective on this type of pain, which is so debilitating to a large number of women.
The Efficacy of Acupuncture on Tic Disorders in Children: A Retrospective and Propensity Score-Matched Study
Authors: You Hai-Zhen , Zhou Yi-Fang , Yu Ping-Bo , Xie Jing , Chen Jia , Li Ji-Jun , Wang Guang-Hai , Sun Ke-Xing 
Published: November 2021

Background : Acupuncture has been considered as a complementary or alternative therapy for children with tic disorders (TD), but its efficacy remains largely unknown. This study retrospectively examined the efficacy of acupuncture treatment for TD in children over the course of 12 weeks.Methods: Data were collected from Traditional Chinese Medicine clinics in a public pediatric hospital in Shanghai between June 2020 and March 2021. A total of 250 patients with TD were included in the study, with 122 patients exposed to acupuncture therapy combined with conventional treatment (observation group), and 128 patients exposed to conventional treatment alone (control group). Propensity score matching analyses were used to balance baseline characteristics, resulting in 78 matched patients for each group. Reductions in the Yale Global Tic Severity Scale (YGTSS) total score were analyzed in the two groups after 12 weeks of treatment.Results: The two groups reached equilibrium in terms of baseline demographic characteristics and YGTSS total score after the propensity score matching (P &gt; 0.05). Compared to the control group, the reduction in the YGTSS total score after 12 weeks of treatment was greater for the observation group (OR = 2.94, 95% CI: 1.03, 8.39, P = 0.04), and this association was stronger for patients who had significant vocal tics (β = 0.29, 95% CI: 0.88, 2.68, P = 0.001). The clinical efficacy for the observation group was significantly better than the control group.Conclusions: We provided preliminary evidence supporting the therapeutic effect of acupuncture for TD in children. Hence, our findings indicate that acupuncture could be an adjuvant treatment efficacious for TD in children, especially for vocal tics.
Short-Term Efficacy and Safety Outcomes of Brolucizumab in the Real-Life Clinical Practice
Authors: Montesel Andrea , Bucolo Claudio , Sallo Ferenc B. , Eandi Chiara M. 
Published: November 2021

To report the early efficacy and safety outcomes of treatment with intravitreal injections of brolucizumab (IVT-B) in patients presenting neovascular age-related macular degeneration (nAMD) in a tertiary clinical setting. A retrospective case series of patients that received IVT-B with a minimum of two injections performed and at least 4 weeks of follow-up after last injection. Nineteen eyes of 19 patients were included. The number of IVT-B performed for the whole cohort was 58 injections; the mean number of IVT-B per patient was 3.0 ± 1.0 (range 2–6); the mean follow-up time was 14.4 ± 9.0 weeks. Mean baseline best-corrected visual acuity was 0.4 ± 0.4 logMAR and at the last follow-up was 0.4 ± 0.6 logMAR (p = 0.778). All eyes showed a reduction in retinal thickness, with the central macular thickness being 470 ± 151 μm at baseline and 360 ± 144 μm at the last follow-up (p = 0.001). Intra-retinal fluid was present at baseline in 12 eyes (63%) and in three eyes (16%) at the last follow-up (p = 0.065). Sub-retinal fluid was present at baseline in 17 eyes (89%) and at the last follow-up in three eyes (16%, p = 0.011). Pigment epithelium detachment was apparent in the 16 eyes (84%) at baseline and was still present in 14 eyes (73%, p = 0.811). One adverse event of intraocular inflammation was reported. In conclusion, our short-term experience showed that brolucizumab was highly effective in restoring the anatomy and in stabilizing the visual acuity of eyes with nAMD. Its safety profile should be evaluated carefully and needs further investigations.