bluuebunny/crossref_metadata_2025_split huggingface dataset:
Six-year clinical outcomes of enzyme replacement therapy for perinatal lethal and infantile hypophosphatasia in Korea: Two case reports
Authors: Kim Insung , Noh Eu-Seon , Kim Min-Sun , Jang Ja-Hyun , Jeon Tae Yeon , Choi Hae Won , Cho Sung Yoon 
Published: February 2023

Introduction:
Hypophosphatasia (HPP) is a genetic disease caused by loss-of-function mutations in ALPL, which encodes tissue-nonspecific alkaline phosphatase (ALP). Early diagnosis and treatment of perinatal and infantile HPP are important because of their high mortality rates. Enzyme replacement therapy (ERT) using human recombinant tissue-nonspecific ALP asfotase alfa was introduced in Korea in 2016. We report the first experience of ERT over 6 years for perinatal lethal and infantile HPP in Korea.

Patient concerns:
The first patient was a 6-week-old Korean boy with a failure to thrive. The second patient was an 8-day-old Korean-Uzbek body with generalized tonic-clonic seizure with cyanosis.

Diagnoses:
HPP was suspected in both patients because of the very low level of ALP activity and rachitic findings on radiographs, and the disease was confirmed by Sanger sequencing of the ALPL gene.

Intervention:
The first patient with infantile HPP started ERT at 21 months of age and the second patient with perinatal HPP started ERT at 30 days of age. Both patients received asfotase alfa (2 mg/kg 3 times per week subcutaneously, adjusted to 3 mg/kg 3 times per week if required) for 6 years.

Outcomes:
After 6 years of ERT, radiographic findings and growth standard deviation scores improved in both patients. The second patient showed no evidence of rickets after 3 years of ERT. Mechanical respiratory support and supplemental oxygen were not required after 4.5 years of treatment in the first patient and at 2 months after treatment in the second patient.

Conclusion:
Among the 2 patients, the patient who started ERT early had a much better prognosis despite a more severe initial clinical presentation. Our results suggest that early diagnosis and prompt treatment play an important role in improving long-term prognosis and avoiding morbidity and premature mortality in patients with perinatal and infantile HPP.
Clinical study of Tongdu Shujin decoction in the treatment of ankylosing spondylitis with cold-dampness obstruction type: Study protocol for a randomized controlled trial
Authors: Wang Zihua , Du Mingrui , Li Jigao , Shi Dongliang , Wang Hejun , Li Huan , Guo Hongtao 
Published: February 2023

Background:
Ankylosing spondylitis (AS) has a high incidence, and severe cases can lead to spinal deformity and even joint fusion, which causes a huge burden on patients life, work and psychology. Tongdu Shujin decoction (TDSJ) has a definite effect in the treatment of ankylosing spondylitis, so we designed a randomized controlled trial to observe the efficacy of TDSJ in the treatment of AS, and to evaluate its safety.

Methods:
In this randomized controlled trial, 80 eligible patients were randomly assigned in a 1:1 ratio to a treatment group TDSJ and a control group (celecoxib capsules in combination with thalidomide tablets) for 8 weeks. Visual analogue scale, bath ankylosing spondylitis disease activity index, bath ankylosing spondylitis functional index, and traditional Chinese medicine syndrome scores will be used as primary indicators. Erythrocyte sedimentation rate, C-reactive protein, spinal mobility (figure-ground distance, occipital tubercle-wall distance, Schober test) will be used as secondary indicators. Vital signs (respiration, heart rate, body temperature, blood pressure, electrocardiogram), blood routine, urine routine, stool routine, liver function, and renal function will be used as safety indicators. The primary and secondary indicators will be detected at 0th and 8th week, while safety indicators at 0th, 4th, and 8th week.

Discussion:
This study will provide high-quality clinical evidence for the efficacy and safety of TDSJ in the treatment of AS.
Effects of intensive speech treatment on Mandarin speakers with Parkinson’s Disease: A review
Authors: Chen Qingqing , Chen Bailin , Wan Qin , Wang Yongli , Li Jian , Huang Zhaoming 
Published: February 2023

Background:
Benefits of intensive speech treatment have been documented for a range of speech signs in English speakers with Parkinson’s Disease (PD). However, the answer to a critical question that whether the same treatment benefits speech variables including intelligibility in Mandarin speakers is still unclear. In order to develop a targeted speech treatment for Mandarin speakers with PD, we reviewed the efficacy of intensive speech treatment to improve vocal loudness and functional communication and discuss possible explanations for efficacy on Mandarin speakers with PD.

Methods:
Literatures about intensive speech treatment for Mandarin speakers with PD were retrieved from PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), Wanfang and Weipu Database for Chinese Technical Periodicals (VIP) Database. Search strategy was (voice therapy OR speech therapy OR voice treatment OR speech treatment OR voice training OR speech training OR voice rehabilitation OR speech rehabilitation OR Lee Silverman voice treatment OR intensive speech treatment) and (Parkinson’s disease) and (Mandarin speakers OR Chinese OR Chinese people).

Results:
Five randomized controlled trials were selected and possible explanations for efficacy on individuals with PD are discussed. Further research directions are suggested.

Conclusion:
The existing evidence from treatment efficacy studies of intensive speech treatment provides support for improving vocal loudness, speech intelligibility, pitch and rate in Mandarin speakers with PD. Our future research will continue to work to conduct a large sample multicenter randomized controlled trial to provide high quality evidence and understand the basic mechanisms accompanying treatment-related change.
Comparison of clinical outcomes with proximal femoral nail anti-rotation versus dynamic hip screw for unstable intertrochanteric femoral fractures: A meta-analysis
Authors: Zhang Cong , Chen Zhangxin , Wang Mengyuan , Chen Wei , Ding Zhenqi 
Published: February 2023

Background:
The aim of this meta-analysis was to evaluate the advantages and disadvantages of proximal femoral nail anti-rotation (PFNA) versus dynamic hip screw (DHS) for the treatment of unstable intertrochanteric fractures, including the available evidence drawn from the literature.

Methods:
A systematic search was conducted to identify available and relevant randomized controlled trials and retrospective comparative observational studies regarding PFNA compared against DHS in treating unstable femoral intertrochanteric fractures in Embase, PubMed, Cochrane Library, Web of Science, and Scopus Online up to February 12, 2022. Data from the included studies were extracted independently by 2 reviewers and analyzed using RevMan 5.3, and the quality of the studies was assessed.

Results:
Five randomized controlled trials and 12 observational studies were recruited and met the inclusion criteria, which consisted of 1332 patients with PFNA and 1271 patients with DHS. The results of the meta-analysis showed that, compared with the DHS, PFNA exhibited a beneficial role in postoperative Harris Hip Scores, operation time, intraoperative blood loss, length of hospital stay, fracture healing time and full weight-bearing time, limb shortening, cutout, reoperation, union problems, the varus collapse of the femoral head/neck, and infection; however, DHS was superior to PFNA in hidden blood loss (relative risk [RR] = 139.81, 95% confidence interval [CI] [136.18, 143.43], P < .00001), postoperation drainage (RR = −17.85, 95% CI [−30.10, −5.60], P = .004), total blood loss (RR = 50.34, 95% CI [42.99, 57.69], P < .00001), and femoral shaft fracture (RR = 4.72, 95% CI [1.15, 19.32], P = .03) treated by DHS were significantly decreased, compared with those by PFNA; however, no significant differences were observed in tip–apex distance, fixation failures, screw migration, or other complicants between the 2 surgical methods.

Conclusion:
Analysis of a large number of relevant clinical indicators available shows that PFNA has better clinical manifestation than DHS in treating unstable femoral intertrochanteric fractures.
Positive Correlation Between 18F-FDG Uptake and Tumor-Proliferating Antigen Ki-67 Expression in Adrenocortical Carcinomas
Authors: Libé Rossella , Pais Aurore , Violon Florian , Guignat Laurence , Bonnet Fideline , Huillard Olivier , Assié Guillaume , Gaillard Martin , Dousset Bertrand , Gaujoux Sébastien , Barat Maxime , Dohan Anthony , Sibony Mathilde , Bertherat Jérôme , Cottereau Anne Segolene , Tenenbaum Florence , Coste Joël , Groussin Lionel 
Published: February 2023

Purpose of the Report
Adrenocortical carcinoma (ACC) is an extremely rare endocrine malignancy, which cannot always be diagnosed during conventional radiology and hormonal investigations. 18F-FDG PET could help predict malignancy, but more data are necessary to support future guidelines.

Methods
A cohort of 63 patients with histologically proven ACC (n = 55) or metastatic ACC with steroid oversecretion (n = 8) was assembled. All patients underwent an 18F-FDG PET, and the SUVmax and the adrenal-to-liver SUVmax ratio were calculated. The 18F-FDG PET parameters were compared with clinical, pathological, and outcome data.

Results
Fifty-six of 63 patients (89%) had an ACC with an adrenal-to-liver SUVmax ratio >1.45, which was a previously defined cutoff value to predict malignancy with 100% sensitivity. Seven ACCs (11%) had a lower uptake (adrenal-to-liver SUVmax <1.45), most of them with a proliferation marker Ki-67 expression level <10%. A positive correlation between 18F-FDG PET parameters (SUVmax and adrenal-to-liver SUVmax ratio) and tumor size, ENSAT (European Network for the Study of Adrenal Tumors) staging, total Weiss score, and the Ki-67 was found. The strong correlation between SUVmax and Ki-67 (r = 0.47, P = 0.0009) suggests a relationship between 18F-FDG uptake levels and tumor proliferation. No statistically significant associations between outcome parameters (progression-free or overall survival) and 18F-FDG PET parameters were found.

Conclusions
This large cohort study shows that most cases of ACC demonstrate high 18F-FDG uptake. However, the positive correlation observed between SUVmax and Ki-67 expression levels seems to explain the possibility of identifying some ACC with a low or inexistent 18F-FDG uptake. These findings have practical implications for the management of patients with an adrenal mass.
Meta-analysis of insomnia, suicide, and psychopathology in schizophrenia
Authors: Miller Brian J. , McCall William V. 
Published: February 2023

Purpose of review
Insomnia is common in schizophrenia. Insomnia has been associated with suicidal ideation and behavior, as well as greater severity of psychopathology, in schizophrenia. This review performs a meta-analysis of associations between insomnia, suicide, and psychopathology in patients with schizophrenia.

Recent findings
We searched major electronic databases from inception until November 2022 for studies of insomnia, suicide, and psychopathology in patients with schizophrenia. Random effects meta-analysis calculating odds ratios (ORs, for suicide) and effect sizes (ESs, for psychopathology) and 95% confidence intervals (CIs) were performed. Ten studies met the inclusion criteria, comprising 3428 patients with schizophrenia. Insomnia was associated with a significant increased odds of suicidal ideation (OR = 1.84, 95% CI 1.28–2.65, P < 0.01) and suicide attempt or death (OR = 5.83, 95% CI 1.61–2.96, P < 0.01). Insomnia was also associated with total (ES = 0.16, 95% CI 0.09–0.23, P < 0.01), positive (ES = 0.14, 95% CI 0.08–0.20, P = 0.02), and general (ES = 0.17, 95% CI 0.08–0.27, P < 0.01) psychopathology. In meta-regression analyses, BMI was negatively associated with suicidal ideation. Otherwise, age, sex, and study year were all unrelated to the associations.

Summary
Insomnia is associated with suicide and psychopathology in schizophrenia. Formal assessment and treatment of insomnia appears relevant to the clinical care of schizophrenia.
Association of Coronary Stenosis with Cerebral Small Vessel Diseases in Neurologically Asymptomatic Adults
Authors: Min Kyungha , Yun Jae-Moon , Hwang Seo Eun , Nam Ki-Woong , Jeong Han-Yeong , Kwon Hyung-Min , Park Jin-Ho 
Published: February 2023

AbstractBackgroundThe high prevalence of coronary stenosis in patients with stroke is well established. However, the association between coronary stenosis and cerebral small vessel diseases (cSVD) in asymptomatic populations remains unclear.MethodsAs a cross-sectional study, we evaluated South Korean adults who underwent a health checkup including brain magnetic resonance imaging and coronary computed tomography angiography between January 2010 and December 2013. The degree of coronary stenosis was classified into three groups: no stenosis (0%), non-significant stenosis (1–49%), and significant stenosis (≥50%). cSVD includes silent lacunar infarction (SLI), cerebral microbleeds (CMB), and white matter hyperintensity (WMH). We used binary logistic regression analyses for SLI and CMB, and linear regression analysis for WMH.ResultsA total of 1,571 participants were evaluated. The prevalence of non-significant and significant coronary stenosis was 369 (23.5%) and 95 (6.1%), respectively. The prevalence of SLI and CMB was 112 (7.1%) and 66 (4.2%), respectively. The mean WMH volume was 2.6 ± 6.1 mL. SLI was significantly associated with both non-significant (adjusted odds ratio [aOR] = 1.94;p= 0.004) and significant coronary stenosis (aOR = 2.37;p= 0.011), even showing dose-response relationship (pfor trend = 0.012). For WMH, only significant coronary stenosis was associated with WMH (β = 0.27;p= 0.013) and had a dose–response relationship (pfor trend = 0.012).ConclusionsThe presence and severity of coronary stenosis were significantly associated with SLI and WMH. Physicians who detects any of coronary stenosis or cSVD should pay attention to the possible coexistence of the other disease.
A Pooled Electronic Consultation Program to Improve Access to Genetics Specialists
Authors: Folkerts Emma K. , Pelletier Renée C. , Chung Daniel C. , Goldstein Susan A. , Micalizzi Douglas S. , Shannon Kristen M. , Sweetser David A. , Wong Eugene K. , Rehm Heidi L. , Hull Leland E. 
Published: February 2023

AbstractInnovative service delivery models are needed to increase access to genetics specialists. Electronic consultation (e-Consult) programs can connect clinicians with specialists. At Massachusetts General Hospital, an e-Consult service was created to address genomics-related questions. In its first year, the e-Consult service triaged 153 requests and completed 122 in an average of 3.2 days. Of the 95 e-Consults with actionable recommendations, there was documentation that most ordering clinicians followed through (82%). A variety of providers used the service, although the majority (77%) were generalists. E-Consult models should be considered as one way to increase access to genetics care.
Oncogenic drivers dictate immune control of acute myeloid leukemia
Authors: Austin Rebecca J. , Straube Jasmin , Halder Rohit , Janardhanan Yashaswini , Bruedigam Claudia , Witkowski Matthew , Cooper Leanne , Porter Amy , Braun Matthias , Souza-Fonseca-Guimaraes Fernando , Minnie Simone A , Cooper Emily , Jacquelin Sebastien , Song Axia , Bald Tobias , Nakamura Kyohei , Hill Geoffrey R. , Aifantis Iannis , Lane Steven W. , Bywater Megan J. 
Published: February 2023

AbstractAcute myeloid leukemia (AML) is a genetically heterogeneous, aggressive hematological malignancy induced by distinct oncogenic driver mutations. The effect of specific AML oncogenes on immune activation or suppression has not been investigated. Here, we examine immune responses in genetically distinct models of AML and demonstrate that specific AML oncogenes dictate immunogenicity, the quality of immune response and immune escape through immunoediting. Specifically, expression of NrasG12Dalone is sufficient to drive a potent anti-leukemia response through increased MHC Class II expression that can be overcome with increased expression of Myc. These data have important implications for the design and implementation of personalized immunotherapies for patients with AML.Statement of SignificanceThe endogenous immune response against acute myeloid leukemia (AML) is determined by leukemia-specific oncogenic driver mutations. Mutant Nras drives immunological selection of AML.
Pharmacodynamic model of PARP1 inhibition and global sensitivity analyses can lead to cancer biomarker discovery
Authors: Mertins Susan D. , Isenberg Natalie M. , Reyes Kristofer-Roy , Yoon Byung-Jun , Urban Nathan , Jogalekar Manasi P. , Diolaiti Morgan E. , Weil M. Ryan , Stahlberg Eric A. 
Published: February 2023

AbstractPharmacodynamic models provide inroads to understanding key mechanisms of action and may significantly improve patient outcomes in cancer with improved ability to determine therapeutic benefit. Additionally, these models may also lead to insights into potential biomarkers that can be utilized for prediction in prognosis and therapeutic decisions. As an example of this potential, here we present an advanced computational Ordinary Differential Equation (ODE) model of PARP1 signalling and downstream effects due to its inhibition. The model has been validated experimentally and further evaluated through a global sensitivity analysis. The sensitivity analysis uncovered two model parameters related to protein synthesis and degradation rates that were also found to contribute the most variability to the therapeutic prediction. Because this variability may define cancer patient subpopulations, we interrogated genomic, transcriptomic, and clinical databases, to uncover a biomarker that may correspond to patient outcomes in the model. In particular, GSPT2, a GTPase with translation function, was discovered and if mutations serve to alter catalytic activity, its presence may explain the variability in the model’s parameters. This work offers an analysis of ODE models, inclusive of model development, sensitivity analysis, and ensuing experimental data analysis, and demonstrates the utility of this methodology in uncovering biomarkers in cancer.Author summaryBecause biochemical reaction networks are complex, dynamic, and typically provide output that results from non-linear interactions, mathematical models of such offer insight into cell function. In the clinic, models including drug action further their usefulness in that they may predict therapeutic outcome and other useful markers such as those for prognosis. In this study, we report a model of drug action that targets a critical protein, that when inhibited, promotes tumor cell death and documented remissions. Because all patients do not respond to the described treatment, a means to find cancer patient subpopulations that might benefit continues to be a challenge. Therefore, we analyzed the pharmacodynamic model by defining the parameters of the greatest variability and interrogated genomic, transcriptomic, and clinical cohort databases with this information and discovered a novel biomarker associated with prognosis in some ovarian and uterine cancer patients and separately, associated with the potential to respond to treatment.
Reelin plasma levels predict cognitive decline in Alcohol Use Disorder: peak levels in patients expressing plasma APOE4 protein
Authors: Escudero Berta , Moya Marta , López-Valencia Leticia , Arias Francisco , Orio Laura 
Published: February 2023

ABSTRACTBackgroundHuman apolipoprotein (APO)-E4 has been related to neuropsychiatric disorders such as Alzheimer’s disease and cognitive decline. Reelin and Clusterin share the VLDLR and ApoER2 receptors with APOE4. Here we checked the role of these components in Alcohol Use Disorder (AUD)-induced cognitive decline.MethodsThis is a cross-sectional study with AUD-diagnosed patients (DSM-5) (n=24) recruited from an outpatient ‘Alcohol Programme’ and matched controls (n=34). Participants were assessed by the validated ‘Test of Detection of Cognitive Impairment in Alcoholism’ (TEDCA). APOE4 presence in plasma (distinguishing APOE4 carriers and no carriers subjects) and its levels were performed by ‘e4Quant’ technique. The rest of biological markers were tested by Enzyme-Linked Immunosorbent Assay kits.ResultsPlasma APOE4 isoform was present in 37.5% and 58.8% of patients and controls, respectively. Quantification analyses revealed that APOE4 reached similar plasma levels in carriers independently if they were AUD subjects or controls. Circulant plasma APOE4 had a negative effect on AUD’s cognition, specifically affecting Memory/Learning (p<0.01, η2=0.15). Plasma Clusterin and Reelin increased in patients but, interestingly, Reelin plasma levels peaked in patients expressing APOE4 (p<0.05, η2=0.09), who showed reduced VLDL and ApoER2 expression in peripheral blood mononuclear cells (PBMCs). Reelin was a good predictor of cognitive loss in patients, accounting for the 42.3% and 54.0% of general intelligence and executive function impairments, respectively.ConclusionsReelin plasma levels are increased in AUD patients who express the APOE4 isoform, predicting cognitive deterioration to a great extent. Remarkably, plasma Reelin helps to differentiate between AUD patients with and without cognitive decline.Significance StatementFinding biological markers that predict a worse evolution in neuropsychiatric disorders may help to assist vulnerable patients appropriately. In this sense, in this study we found a biological marker, Reelin, which is elevated in patients with diagnosis of alcohol use disorder (AUD) that underwent an outpatient treatment. Interestingly, Reelin plasma levels were elevated in patients that also express APOE4, an aberrant protein present only in a small percentage of the population which is related to neuroinflammation and cognitive impairment (i.e. it is involved in Alzheimer’s disease). We observed that Reelin plasma levels negatively correlate with cognitive scores, being Reelin a good predictor of cognitive impairment in patients. These results may have implications for the follow-up of AUD patients in outpatient treatment.