bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frequent somatic mosaicism in T lymphocyte subsets in individuals with and without multiple sclerosis
Authors: Van Horebeek Lies , Dedoncker Nina , Dubois Bénédicte , Goris An 
Published: December 2022

BackgroundSomatic variants are variations in an individual’s genome acquired after the zygotic stadium and result from mitotic errors or not (fully) repaired DNA damage.ObjectivesTo investigate whether somatic mosaicism in T lymphocyte subsets is enriched early in multiple sclerosis (MS).MethodsWe identified somatic variants with variant allele fractions ≥1% across the whole exome in CD4+ and CD8+ T lymphocytes of 21 treatment-naive MS patients with &lt;5 years of disease duration and 16 partially age-matched healthy controls. We investigated the known somatic STAT3 variant p.Y640F in peripheral blood in a larger cohort of 446 MS patients and 259 controls.ResultsAll subjects carried 1-142 variants in CD4+ or CD8+ T lymphocytes. Variants were more common, more abundant, and increased with age in CD8+ T lymphocytes. Somatic variants were common in the genes DNMT3A and especially STAT3. Overall, the presence or abundance of somatic variants, including the STAT3 p.Y640F variant, did not differ between MS patients and controls.ConclusionsSomatic variation in T lymphocyte subsets is widespread in both control individuals and MS patients. Somatic mosaicism in T lymphocyte subsets is not enriched in early MS and thus unlikely to contribute to MS risk, but future research needs to address whether a subset of variants influences disease susceptibility.
Differences in retinal microvasculature between large artery atherosclerosis and small artery disease: an optical coherence tomography angiography study
Authors: Lu Kun , Kwapong William Robert , Jiang Shuai , Zhang Xuening , Xie Jianyang , Ye Chen , Yan Yuying , Cao Le , Zhao Yitian , Wu Bo 
Published: December 2022

Purpose: Recent reports suggest retinal microvasculature mirror cerebral microcirculation. Using optical coherence tomography angiography (OCTA), we investigated the retinal microvasculature differences between ischemic stroke patients with large artery atherosclerosis (LAA) and small artery disease (SAD).Methods: All patients underwent MR imaging and were classified as SAD and LAA; LAA was subdivided into anterior LAS and posterior LAS depending on the location. Swept-source OCTA (SS-OCTA) was used to image and segment the retina into the superficial vascular complex (SVC) and deep vascular complex (DVC) in a 6 × 6 mm area around the fovea. A deep learning algorithm was used to assess the vessel area density (VAD, %) in the retinal microvasculature.Results: Fifty-eight (mean age = 60.26 ± 10.88 years; 81.03% males) were LAA while 64 (mean age = 55.58 ± 10.34 years; 85.94% males) were SAD. LAS patients had significantly reduced VAD in the DVC (P = 0.022) compared to SAD patients; the VAD in the SVC did not show any significant difference between the two groups (P = 0.580). Anterior LAA ischemic stroke showed significantly lower VAD (P = 0.002) in the SVC compared with posterior LAS patients. There was no significant difference in the DVC between the two groups (P = 0.376).Conclusions: We found LAA patients had significantly reduced DVC density compared with SAD; we also showed anterior LAA patients had significantly reduced SVC density compared with posterior LAA. These findings suggest retinal imaging has the potential to be used to detect microvasculature changes in subtypes of ischemic stroke.
Validation of the GALAD model and establishment of a new model for HCC detection in Chinese patients
Authors: Chen Ping , Song Haolin , Xu Wei , Guo Jin , Wang Jianfei , Zhou Juhong , Kang Xiang , Jin Chaolei , Cai Yubo , Feng Zixuan , Gao Hainv , Lu Fengmin , Li Lanjuan 
Published: December 2022

BackgroundGALAD model is a statistical model used to estimate the possibility of hepatocellular carcinoma (HCC) in patients with chronic liver disease. Many studies with other ethnic populations have shown that it has high sensitivity and specificity. However, whether this model can be used for Chinese patients remains to be determined. Our study was conducted to verify the performance of GALAD model in a Chinese cohort and construct a new model that is more appropriately for Chinese populations.MethodsThere are total 512 patients enrolled in the study, which can be divided into training set and validation set. 80 patients with primary liver cancer, 139 patients with chronic liver disease and 87 healthy people were included in the training set. Through the ROC(receiver operating characteristic) curve analysis, the recognition performance of GALAD model for liver cancer was evaluated, and the GAADPB model was established by logistic regression, including gender, age, AFP, DCP, total protein, and total bilirubin. The validation set (75 HCC patients and 130 CLD patients) was used to evaluate the performance of the GAADPB model.ResultThe GALAD and GAADPB achieved excellent performance (area under the receiver operating characteristic curve [AUC], 0.925, 0.945), and were better than GAAP, Doylestown, BALAD-2, aMAP, AFP, AFP-L3%, DCP and combined detection of AFP, AFP-L3 and DCP (AUCs: 0.894, 0.870, 0.648, 0.545, 0.879, 0.782, 0.820 and 0.911) for detecting HCC from CLD in the training set. As for early stage of HCC (BCLC 0/A), GAADPB had the best sensitivity compared to GALAD, ADP and DCP (56.3%, 53.1%, 40.6%, 50.0%). GAADPB had better performance than GALAD in the test set, AUC (0.896 vs 0.888).ConclusionsThe new GAADPB model was powerful and stable, with better performance than the GALAD and other models, and it also was promising in the area of HCC prognosis prediction. Further study on the real-world HCC patients in China are needed.
Abdominoinguinal approach in en bloc resection of retroperitoneal sarcoma involving iliac vessels with graft interposition
Authors: Lv Ang , Liu Bo-Nan , Liu Dao-Ning , Wang Zhen , Hao Chun-Yi 
Published: December 2022

BackgroundRetroperitoneal sarcomas (RPSs) located in the lower abdominal quadrants involving iliac vessels are difficult to manage. This study introduced a 5-step method for en bloc resection with graft interposition using the abdominoinguinal approach and evaluated its efficacy and safety.MethodsData of 24 consecutive patients who met the inclusion criteria from 272 patients with RPS who underwent surgical treatment between April 2015 and April 2022 were retrospectively collected and analyzed.ResultsThe patients underwent left- or right-sided abdominoinguinal incision. In all patients, the abdominoinguinal approach provided good exposure, and complete resection was achieved. Iliac artery+vein, vein, and artery resection and replacement by graft were performed in 70.8%, 25.0%, and 4.2% of patients, respectively. Additional resected organs mainly included the colon, ureter, bladder, kidney, and abdominal wall. The median number of organs resected was 5. In 37.5% of patients, reconstruction of the lower abdominal wall and inguinal ligament was performed using a mesh. Venous graft thrombosis occurred in 21.7% of patients, while no patient had pulmonary embolism or arterial occlusion. Major complications occurred in 20.8% of patients, and no 30-day mortality was observed. The estimated 5-year local recurrence and distant metastasis rates were 54.4% and 22.1%, respectively, with a median recurrence-free survival of 27 months.ConclusionsEn bloc resection of RPS involving iliac vessels with graft interposition using the abdominoinguinal approach is feasible and advantageous. Good complete resection rate and safety can be achieved. The long-term survival benefit of this surgical approach should be verified by further large-scale prospective controlled studies.
Dinutuximab beta plus conventional chemotherapy for relapsed/refractory high-risk neuroblastoma: A single-center experience
Authors: Olgun Nur , Cecen Emre , Ince Dilek , Kizmazoglu Deniz , Baysal Birsen , Onal Ayse , Ozdogan Ozhan , Guleryuz Handan , Cetingoz Riza , Demiral Ayse , Olguner Mustafa , Celik Ahmet , Kamer Serra , Ozer Erdener , Altun Zekiye , Aktas Safiye 
Published: December 2022

BackgroundRelapsed/refractory high-risk neuroblastoma has a dismal prognosis. Anti-GD2-mediated chemo-immunotherapy has a notable anti-tumor activity in patients with relapsed/refractory high-risk neuroblastoma. The purpose of this study was to analyze the efficacy and safety of the combination of immunotherapy with dinutuximab beta (DB) and chemotherapy in patients with relapsed/refractory high-risk neuroblastoma.MethodsAll patients received the Turkish Pediatric Oncology Group NB 2009 national protocol for HR-NB treatment at the time of diagnosis. Salvage treatments were administered after progression or relapse. The patients who could not achieve remission in primary or metastatic sites were included in the study. The most common chemotherapy scheme was irinotecan and temozolomide. DB was administered intravenously for 10 days through continuous infusion with 10 mg/m2 per day. The patients received 2 to 14 successive cycles with duration of 28 days each. Disease assessment was performed after cycles 2, 4, and 6 and every 2 to 3 cycles thereafter.ResultsBetween January 2020 and March 2022, nineteen patients received a total of 125 cycles of DB and chemotherapy. Objective responses were achieved in 12/19 (63%) patients, including complete remission in 6/19 and partial response in 6/19. Stable disease was observed in two patients. The remaining five patients developed bone/bone marrow and soft tissue progression after 2-4 cycles of treatment. The most common Grade ≥3 toxicities were leukopenia, thrombocytopenia, hypertransaminasemia, fever, rash/itching and capillary leak syndrome, respectively.ConclusionOur study results suggest that DB-based chemo-immunotherapy seems to be suitable with encouraging response rates in patients with relapsed/refractory high-risk neuroblastoma.
Multi-analyte liquid biopsies for molecular pathway guided personalized treatment selection in advanced refractory cancers: A clinical utility pilot study
Authors: Patil Darshana , Akolkar Dadasaheb , Nagarkar Rajnish , Srivastava Navin , Datta Vineet , Patil Sanket , Apurwa Sachin , Srinivasan Ajay , Datar Rajan 
Published: December 2022

PurposeThe selection of safe and efficacious anticancer regimens for treatment of patients with broadly refractory metastatic cancers remains a clinical challenge. Such patients are often fatigued by toxicities of prior failed treatments and may have no further viable standard of care treatment options. Liquid Biopsy-based multi-analyte profiling in peripheral blood can identify a majority of drug targets that can guide the selection of efficacious combination regimens.Patients and methodsLIQUID IMPACT was a pilot clinical study where patients with advanced refractory cancers received combination anticancer treatment regimens based on multi-analyte liquid biopsy (MLB) profiling of circulating tumor biomarkers; this study design was based on the findings of prior feasibility analysis to determine the abundance of targetable variants in blood specimens from 1299 real-world cases of advanced refractory cancers.ResultsAmong the 29 patients in the intent to treat (ITT) cohort of the trial, 26 were finally evaluable as per study criteria out of whom 12 patients showed Partial Response (PR) indicating an Objective Response Rate (ORR) of 46.2% and 11 patients showed Stable Disease (SD) indicating the Disease Control Rate (DCR) to be 88.5%. The median Progression-Free Survival (mPFS) and median Overall Survival (mOS) were 4.3 months (95% CI: 3.0 – 5.6 months) and 8.8 months (95% CI: 7.0 – 10.7 months), respectively. Toxicities were manageable and there were no treatment-related deaths.ConclusionThe study findings suggest that MLB could be used to assist treatment selection in heavily pretreated patients with advanced refractory cancers.
Improvement of the gait pattern after selective dorsal rhizotomy derives from changes of kinematic parameters in the sagittal plane
Authors: Jiang Wenbin , Jiang Shuyun , Yu Yan , Zhan Qijia , Wei Min , Mei Rong , Chen Fang , Guo Yao , Xiao Bo 
Published: December 2022

ObjectiveSelective dorsal rhizotomy (SDR) can decrease spasticity in children suffering from spastic cerebral palsy (SCP) and thus improve their moving ability when supplemented with the post-operational rehabilitation program. In this case, the study aims to investigate the gait changes in children with mild SCP after SDR in short-term follow-up.MethodsThe information of ambulatory SCP cases who underwent SDR in our center was retrospectively reviewed, and comparisons of changes in spasticity, motor function and data of gait analysis before and after SDR were analyzed.ResultsIn total, 32 cases were included in this study, with a mean age of 5.9 ± 2.1 years old. Noticeable decrease was found in the median value of the pre-operational MAS score after SDR at last follow-up in both sides of adductors, gastrocnemius, soleus, and left hamstrings. The Gross Motor Function Measure-66 score increased from 70.6 ± 9.2 to 73.4 ± 8.2, and the gait deviation index increased after SDR compared with the pre-operational data (right side: 65.8 ± 8.8 vs. 60.1 ± 10.7; left side: 63.5 ± 10.1 vs. 57.0 ± 9.9). Noticeable changes were found that the maximum angle of affected ankles in the sagittal plane (the dorsal-flexion angle) increased from 2.5° to 8.2°, the angles at initial contact (1% gait cycle) of affected knees in the sagittal plane decreased from 34.0° to 27.8°, and the angles at the end of swing phase (100% gait cycle) of affected knees in the sagittal plane decreased from 35.8° to 28.3°.ConclusionIn short-term follow-up, SDR can lower spasticity in children with SCP. Post-operational gait analysis showed improvements in gross motor function and gait, which derived from the changes in the sagittal plane (ankle and knee). A longer follow-up duration is thus needed to clarify the long-term outcome.
The effects of qishen granules for patients with chronic heart failure: A multicenter randomized double-blind placebo-controlled trial
Authors: Du Kangjia , Liu Junjie , Tan Nannan , Huang Xinyi , Wang Juan , Zhao Huihui , Wang Wei 
Published: December 2022

Background: Despite advancements in chronic heart failure (CHF) treatment, the effect often remains unsatisfactory and unstable. More effective therapies are needed. Qishen granules (QSG) are a novel Chinese botanical drug effective in treating CHF in animal models, but clinical evidence remains inadequate.Objective: This study aims to evaluate the effects of QSG on patients with CHF.Methods: We enrolled CHF patients in this 12-week, randomized, double-blind, placebo-controlled trial and randomly assigned them to the QSG (twice a day, 6.8 g granules at once) or placebo group. The primary endpoint was a change in the plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) level after treatment. The secondary outcome consists of the New York Heart Association (NYHA) functional classification, 6-min walking distance (6MWD), TCM syndrome integral scale, quality of life, and echocardiographic index.Results: A total of 191 patients completed the 12-week follow-up period, with 94 in the QSG group and 97 in the placebo group. The Qishen granules group demonstrated a considerably greater reduction in NT-proBNP than the placebo group (50% vs 32% for QSG vs placebo, respectively; p = 0.011). Patients who received QSG performed better in the NYHA functional rank, 6MWD, TCM syndrome integral scale, and quality of life (p &lt; 0.05). The QSG group performed better in HFrEF patients regarding the efficiency of NT-proBNP. There was no statistical significance in the change in evaluated safety parameters, such as blood routine and biochemistry.Conclusion: Based on standard treatment, Qishen granules further reduced the levels of NT-proBNP when compared with placebo. Together with other outcomes, our findings suggest that QSG could be used in combination therapy for CHF.Clinical Trial Registration: www.clinicaltrials.gov, identifier NCT03027375. Registered 9 October 2017
Ultrasonic optic nerve sheath diameter could improve the prognosis of acute ischemic stroke in the intensive care unit
Authors: Li Cong , Wang Cui-Cui , Meng Yan , Fan Jia-Yu , Zhang Jie , Wang Li-Juan 
Published: December 2022

Objectives: Stroke patients with high intracranial pressure (ICP) may have poor prognosis. Non-invasive ultrasonic optic nerve sheath diameter (ONSD) could evaluate increased ICP. To investigate whether ONSD is valuable for prognosis of patients with acute ischemic stroke (AIS).Methods: AIS receiving intensive care were recruited with the Glasgow Coma Scale (GCS) score. Patients in group A underwent ultrasonic ONSD to assess ICP voluntarily, whereas group B without ONSD. Patients were followed up at discharge and once a week for 3 months with Glasgow Outcome Scale (GOS) score (four to five scores indicated good prognosis and one to three scores indicated poor prognosis).Results: Forty-nine patients were included. GCS scores did not differ significantly between groups A (26 patients) and B (8 ± 3 vs. 7 ± 3, p &lt; 0.05). In group A, ONSD was 5.01 ± 0.48 mm, which correlated with GCS score (p &lt; 0.05). At discharge, the GOS score was higher in group A than in group B (3.35 ± 1.35 vs. 2.57 ± 1.121, p = 0.034). The proportion of patients with a good prognosis was higher in group A than in group B (46.2% vs. 13.0%, p = 0.006). At discharge and after 3 months of follow-up, ONSD at admission was correlated with the GOS score in group A (r = -0.648 [p &lt; 0.05] and -0.731 [p &lt; 0.05], respectively). After 3 months of follow-up, the GOS score was higher in group A than group B (3.00 ± 1.673 vs. 2.04 ± 1.430, p &lt; 0.05). The proportion of patients with a good prognosis was higher in group A than in group B (46.2% vs. 21.2%, p = 0.039). The Kaplan-Meier curve showed a higher rate of good prognosis in group A than in group B. ONSD (p &lt; 0.05) was an independent predictor of poor prognosis.Conclusion: Non-invasive ultrasonic ONSD could be useful in improving the prognosis of patients with AIS receiving intensive care.
A case report of severe pirimiphos-methyl intoxication: Clinical findings and cholinesterase status
Authors: Zellner Tobias , Rabe Christian , Wellen-Pawlowski Jens von der , Hansen Dagmar , John Harald , Worek Franz , Eyer Florian 
Published: December 2022

A 63-year-old male was admitted to a district hospital after ingesting ethanol and pirimiphos-methyl (PM) with suicidal intentions. History included alcoholic cirrhosis with alcoholism, adiposity, diabetes with cerebral microangiopathy, chronic renal insufficiency, heparin-induced thrombocytopenia, and status post necrotizing fasciitis. Emergency medical service reported an alert patient without signs of cholinergic crisis; activated charcoal and atropine were administered. Upon hospital arrival, he received fluid resuscitation, activated charcoal, and atropine. He was transferred to a toxicology unit the next day. On admission, he had no cholinergic signs (dry mucous membranes, warm skin, and mydriatic pupils) requiring small atropine doses (0.5 mg per hour). Four hours after admission, he developed bradycardia and respiratory distress, necessitating intubation. He received atropine by continuous infusion for 7 days (248 mg total) and obidoxime (bolus and continuous infusion). PM, pirimiphos-methyl-oxon (PMO), and phosphorylated tyrosine (Tyr) adducts derived from human serum albumin were analyzed in vivo. Cholinesterase status (acetylcholinesterase (AChE), butyrylcholinesterase (BChE), inhibitory activity of patient plasma and reactivatability, and phosphorylated BChE-derived nonapeptides) was measured in vivo. Obidoxime and atropine were monitored. PM and PMO were detectable, PM with maximum concentration ∼24 h post admission (p.a.) and PMO at ∼18 h p.a. Tyr adducts were detectable. AChE in vivo was suppressed on admission, increased continuously after starting obidoxime, and reached maximum activity after ∼30 h. AChE in vivo and reactivatability remained at the same level until the end of monitoring. BChE was already suppressed on admission; termination of the antidote treatment was possible after BChE had recovered to 1/5th of its normal value and extubation was possible after BChE had recovered to 2/5th. While a substantial part of BChE was already aged on admission, aging continued peaking at ∼24 h p.a. After initiating obidoxime treatment, plasma levels increased until obidoxime plasma levels reached a steady state. On admission, plasma atropine level was low; it increased with the start of the continuous infusion. Afterward, the level dropped to a steady state. The clinical course was characterized by bouts of pneumonia, necessitating re-intubation and prolonged ventilation, sepsis, delirium, and a peripheral neuropathy. After psychiatric evaluation, the patient was discharged to a neurological rehabilitation facility after 77 days of hospital care.
A 10 bit 1 MS/s SAR ADC with one LSB common-mode shift energy-efficient switching scheme for image sensor
Authors: Hu Yunfeng , Hu Lexing , Tang Bin , Yi Zichuan 
Published: December 2022

A 10 bit 1 MS/s SAR ADC with one LSB common-mode shift energy-efficient switching scheme for image sensor is presented. Based on the two sub-capacitor arrays architecture and the common-mode technique, the proposed switching scheme achieves 98.45% less switching energy over the conventional architecture with common-mode shift in one LSB. The comparator uses a low power dynamic comparator. The sampling switch adopts a bootstrap circuit with low sampling error. SAR logic is composed of Bit-Slice circuit with low power consumption and few transistors. Simulated in 180 nm CMOS process and 1 MS/s sampling rate, the ADC achieves the 60.06 dB SNDR, the 75.43 dB SFDR and the 10.45 μW power consumption.