bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneous early illness courses of Korean patients with bipolar disorders: replication of the staging model
Authors: Lee Yejin , Lee Dongbin , Jung Hyewon , Cho Yunji , Baek Ji Hyun , Hong Kyung Sue 
Published: November 2022

Abstract
Background
Clinical staging of bipolar disorder (BD) requires application of real-world data, as the next step in hypothesis. This study used the staging model to analyze the long-term course of BD in Korean patients based on clinical features and treatment responses to map the progression of bipolar illness from its early phase after the onset of illness.

Methods
A total of 136 patients diagnosed with BD-I (n = 62) or BD-II (n = 74) were recruited. Their progressive stages were retrospectively evaluated. A multi-state model was used to calculate the probability of progression to each stage. Hazard ratios of covariates expected to influence different courses of BD were calculated. Using the Alda score, long-term responses to mood stabilizers depending on the current stage were compared.

Results
Several sub-populations showed varied courses during the first five years after the onset of illness, with 41.5% remaining in stage 2 and 53% progressing to higher stages with shortened time for transition. Profiles of patients with BD-I and BD-II were different, suggesting biologically distinct groups. Comorbid psychiatric disorders, such as obsessive-compulsive disorder (OCD) and bulimia nervosa (BN) were associated with a recurrent course (stage 3a or 3b) or a malignant course (stage 3c or 4). Early age of onset, shorter duration of illness, older age at the start of medication, and poor response to lithium affected the illness progression.

Conclusion
We were able to apply the stage model based on episode recurrence patterns in early illness courses of Korean patients with BD. The stage progression pattern differed from the early phase in BD-I and BD-II patients. Psychotic comorbidity, age at onset, age at starting psychiatric treatment showed associations with the illness progression.
Identification, expression, and purification of DNA cytosine 5-methyltransferases with short recognition sequences
Authors: Miura Fumihito , Miura Miki , Shibata Yukiko , Furuta Yoshikazu , Miyamura Keisuke , Ino Yuki , Bayoumi Asmaa M. A. , Oba Utako , Ito Takashi 
Published: November 2022

Abstract
Background
DNA methyltransferases (MTases) are enzymes that induce methylation, one of the representative epigenetic modifications of DNA, and are also useful tools for analyzing epigenomes. However, regarding DNA cytosine 5-methylation, MTases identified so far have drawbacks in that their recognition sequences overlap with those for intrinsic DNA methylation in mammalian cells and/or that the recognition sequence is too long for fine epigenetic mapping. To identify MTases with short recognition sequences that never overlap with the CG dinucleotide, we systematically investigated the 25 candidate enzymes identified using a database search, which showed high similarity to known cytosine 5-MTases recognizing short sequences.

Results
We identified MTases with six new recognition sequences, including TCTG, CC, CNG, TCG, GCY, and GGCA. Because the recognition sequence never overlapped with the CG dinucleotide, MTases recognizing the CC dinucleotide were promising.

Conclusions
In the current study, we established a procedure for producing active CC-methylating MTases and applied it to nucleosome occupancy and methylome sequencing to prove the usefulness of the enzyme for fine epigenetic mapping. MTases that never overlap with CG dinucleotides would allow us to profile multiple epigenomes simultaneously.
Implementation of Coach McLungsSM into primary care using a cluster randomized stepped wedge trial design
Authors: Ludden Thomas , O’Hare Katherine , Shade Lindsay , Reeves Kelly , Patterson Charity G. , Tapp Hazel 
Published: November 2022

Abstract
Background
Asthma is a prevalent chronic disease that is difficult to manage and associated with marked disparities in outcomes. One promising approach to addressing disparities is shared decision making (SDM), a method by which the patient and provider cooperatively make a decision about asthma care. SDM is associated with improved outcomes for patients; however, time constraints and staff availability are noted implementation barriers. Use of health information technology (IT) solutions may facilitate the utilization of SDM. Coach McLungsSM is a collaborative web-based application that involves pediatric patients, their caregivers, and providers in a personalized experience while gathering patient-reported data. Background logic provides decision support so both audiences can develop a well-informed treatment plan together. The goal of this study is to evaluate the implementation of the Coach McLungsSM intervention into primary care.

Methods
Implementation will be evaluated using a stepped wedge randomized control study design at 21 pediatric and family medicine practices within a large, integrated, nonprofit healthcare system. We will measure changes in emergency department visits, hospitalizations, and oral steroid use, which serve as surrogate measures for patient-centered asthma outcomes. We will use a generalized linear mixed models with logit link to test the hypothesis for the reduction in exacerbation rates specifying the fixed effects of intervention and time and random effects for practice and practice*time. This design achieves 84% power to detect the hypothesized effect size difference of 10% in overall exacerbation between control (40%) and intervention (30%) periods (two-sided, p = 0.05). Implementation will be guided using the Expert Recommendations for Implementing Change (ERIC), a compilation of implementation strategies, and evaluated using the CFIR (Consolidated Framework for Implementation Research) and RE-AIM (Reach Effectiveness, Adoption, Implementation, Maintenance).

Discussion
We anticipate that a tailored implementation of Coach McLungsSM across diverse primary care practices will lead to a decrease in emergency department visits, hospitalizations, and oral steroid use for patients in the intervention group as compared to the control condition.
Trial Registration: Clincaltrials.gov, NCT05059210. Registered 28 September 2021, https://www.clinicaltrials.gov/ct2/show/NCT05059210
Safety and efficacy of corticosteroids in ARDS patients: a systematic review and meta-analysis of RCT data
Authors: Chang Xinyan , Li Shaojun , Fu Yueqiang , Dang Hongxing , Liu Chengjun 
Published: November 2022

Abstract
Purpose
Acute respiratory distress syndrome (ARDS) is an acute and critical disease among children and adults, and previous studies have shown that the administration of corticosteroids remains controversial. Therefore, a meta-analysis of randomized controlled trials (RCTs) was performed to evaluate the safety and efficacy of corticosteroids.

Methods
The RCTs investigating the safety and efficacy of corticosteroids in ARDS were searched from electronic databases (Embase, Medline, and the Cochrane Central Register of Controlled Trials). The primary outcome was 28-day mortality. Heterogeneity was assessed using the Chi square test and I2 with the inspection level of 0.1 and 50%, respectively.

Results
Fourteen RCTs (n = 1607) were included for analysis. Corticosteroids were found to reduce the risk of death in patients with ARDS (relative risk (RR) = 0.78, 95% confidence interval (CI): 0.70–0.87; P < 0.01). Moreover, no significant adverse events were observed, compared to placebo or standard support therapy. Further subgroup analysis showed that variables, such as adults (RR = 0.78; 95% CI: 0.70–0.88; P < 0.01), non-COVID-19 (RR = 0.71; 95% CI: 0.62–0.83; P < 0.01), methylprednisolone (RR = 0.70; 95% CI: 0.56–0.88; P < 0.01), and hydrocortisone (RR = 0.79; 95% CI: 0.63–0.98; P = 0.03) were associated with 28-day mortality among patients who used corticosteroids. However, no association was found, regarding children (RR = 0.21; 95% CI: 0.01–4.10; P = 0.30).

Conclusion
The use of corticosteroids is an effective approach to reduce the risk of death in ARDS patients. However, this effect is associated with age, non-COVID-19 diseases, and methylprednisolone and hydrocortisone use. Therefore, evidence suggests patients with age ≥ 18 years and non-COVID-19 should be encouraged during the corticosteroid treatment. However, due to substantial differences in the use of corticosteroids among these studies, questions still remain regarding the dosage, optimal corticosteroid agent, and treatment duration in patients with ARDS.
Association of angiotensin-converting enzyme insertion/deletion (ACE I/D) gene polymorphism with susceptibility to prostate cancer: an updated meta-analysis
Authors: Du Jianhui , Lan Jianhua , Yang Hai , Ying Qiao , Huang Guohua , Mou Jian , Long Jia , Qiao Zhenghua , Hu Qiyi 
Published: November 2022

Abstract
Objective
This meta-analysis aims to explore the association between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and susceptibility to prostate cancer (PCa).

Methods
We searched studies related to ACE I/D polymorphism and susceptibility to PCa through PubMed, Web of Science, Embase, Cochrane Library, and Scopus databases from inception to June 1, 2022. Five gene models, including allelic, dominant, recessive, homozygote, and heterozygote models, were analyzed. The pooled odds ratio (OR) was calculated using Stata 15.0 software. Publication bias was judged by the funnel plot and Egger’s test, with the robustness of the findings verified by sensitivity analysis.

Results
Eight published articles (including ten studies) were identified. The pooled results showed that ACE I/D locus polymorphism was significantly correlated with the risk of PCa under all gene models except for the heterozygous model (D vs. I: OR= 1.58, 95% CI: 1.14–2.21; DD vs. DI+II: OR=1.68, 95% CI: 1.11–2.54; DD+DI vs. II: OR=1.76, 95% CI: 1.11–2.80; DI vs. II: OR= 1.44, 95% CI: 0.99–2.10; DD vs. II: OR= 2.12, 95% CI: 1.15–3.93). Subgroup analysis based on genotype frequencies in the control group meeting Hardy-Weinberg equilibrium showed statistically significant differences in all gene models. The funnel plot and Egger’s test indicated no publication bias. The sensitivity analysis verified the robustness of the conclusions obtained in this meta-analysis.

Conclusion
ACE I/D locus polymorphism correlates to PCa risk. Allele D, genotype DD+DI, and DD at the ACE I/D locus increase susceptibility to PCa and can therefore serve as a potential diagnostic and screening molecular marker for PCa patients.
Longitudinal phenotypes in patients with acute respiratory distress syndrome: a multi-database study
Authors: Chen Hui , Yu Qian , Xie Jianfeng , Liu Songqiao , Pan Chun , Liu Ling , Huang Yingzi , Guo Fengmei , Qiu Haibo , Yang Yi 
Published: November 2022

Abstract
Background
Previously identified phenotypes of acute respiratory distress syndrome (ARDS) have been limited by a disregard for temporal dynamics. We aimed to identify longitudinal phenotypes in ARDS to test the prognostic and predictive enrichment of longitudinal phenotypes, and to develop simplified models for phenotype identification.

Methods
We conducted a multi-database study based on the Chinese Database in Intensive Care (CDIC) and four ARDS randomized clinical trials (RCTs). We employed latent class analysis (LCA) to identify longitudinal phenotypes using 24-hourly data from the first four days of invasive ventilation. We used the Cox regression model to explore the association between time-varying respiratory parameters and 28-day mortality across phenotypes. Phenotypes were validated in four RCTs, and the heterogeneity of treatment effect (HTE) was investigated. We also constructed two multinomial logistical regression analyses to develop the probabilistic models.

Findings
A total of 605 ARDS patients in CDIC were enrolled. The three-class LCA model was identified and had the optimal fit, as follows: Class 1 (n = 400, 66.1% of the cohort) was the largest phenotype over all study days, and had fewer abnormal values, less organ dysfunction and the lowest 28-day mortality rate (30.5%). Class 2 (n = 102, 16.9% of the cohort) was characterized by pulmonary mechanical dysfunction and had the highest proportion of poorly aerated lung volume, the 28-day mortality rate was 47.1%. Class 3 (n = 103, 17% of the cohort) was correlated with extra-pulmonary dysfunction and had the highest 28-day mortality rate (56.3%). Time-varying mechanical power was more significantly associated with 28-day mortality in Class 2 patients compared to other phenotypes. Similar phenotypes were identified in four RCTs. A significant HTE between phenotypes and treatment strategies was observed in the ALVEOLI (high PEEP vs. low PEEP) and the FACTT trials (conservative vs. liberal fluid management). Two parsimonious probabilistic models were constructed to identify longitudinal phenotypes.

Interpretation
We identified and validated three novel longitudinal phenotypes for ARDS patients, with both prognostic and predictive enrichment. The phenotypes of ARDS can be accurately identified with simple classifier models, except for Class 3.
Genistein effect on cognition in prodromal Alzheimer’s disease patients. The GENIAL clinical trial
Authors: Viña José , Escudero Joaquín , Baquero Miquel , Cebrián Mónica , Carbonell-Asíns Juan Antonio , Muñoz José Enrique , Satorres Encarnación , Meléndez Juan Carlos , Ferrer-Rebolleda José , Cózar-Santiago Mª del Puig , Santabárbara-Gómez Jose Manuel , Jové Mariona , Pamplona Reinald , Tarazona-Santabalbina Francisco José , Borrás Consuelo 
Published: November 2022

Abstract
Background
Delaying the transition from minimal cognitive impairment to Alzheimer’s dementia is a major concern in Alzheimer’s disease (AD) therapeutics.
Pathological signs of AD occur years before the onset of clinical dementia. Thus, long-term therapeutic approaches, with safe, minimally invasive, and yet effective substances are recommended. There is a need to develop new drugs to delay Alzheimer’s dementia. We have taken a nutritional supplement approach with genistein, a chemically defined polyphenol that acts by multimodal specific mechanisms. Our group previously showed that genistein supplementation is effective to treat the double transgenic (APP/PS1) AD animal model.

Methods
In this double-blind, placebo-controlled, bicentric clinical trial, we evaluated the effect of daily oral supplementation with 120 mg of genistein for 12 months on 24 prodromal Alzheimer’s disease patients. The amyloid-beta deposition was analyzed using 18F-flutemetamol uptake. We used a battery of validated neurocognitive tests: Mini-Mental State Exam (MMSE), Memory Alteration Test (M@T), Clock Drawing Test, Complutense Verbal Learning Test (TAVEC), Barcelona Test-Revised (TBR), and Rey Complex Figure Test.

Results
We report that genistein treatment results in a significant improvement in two of the tests used (dichotomized direct TAVEC, p = 0.031; dichotomized delayed Centil REY copy p = 0.002 and a tendency to improve in all the rest of them.
The amyloid-beta deposition analysis showed that genistein-treated patients did not increase their uptake in the anterior cingulate gyrus after treatment (p = 0.878), while placebo-treated did increase it (p = 0.036). We did not observe significant changes in other brain areas studied.

Conclusions
This study shows that genistein may have a role in therapeutics to delay the onset of Alzheimer’s dementia in patients with prodromal Alzheimer’s disease. These encouraging results indicate that this should be followed up by a new study with more patients to further validate the conclusion that arises from this study.

Trial registration
NCT01982578, registered on November 13, 2013.
Impact of suboptimal or inappropriate treatment on healthcare resource use and cost among patients with uncomplicated urinary tract infection: an analysis of integrated delivery network electronic health records
Authors: Shafrin Jason , Marijam Alen , Joshi Ashish V. , Mitrani-Gold Fanny S. , Everson Katie , Tuly Rifat , Rosenquist Peter , Gillam Michael , Ruiz Maria Elena 
Published: November 2022

Abstract
Background
Although uncomplicated urinary tract infections (uUTIs; occurring in female patients without urological abnormalities or history of urological procedures or complicating comorbidities) are one of the most common community infections in the United States (US), limited data are available concerning associations between antibiotic resistance, suboptimal prescribing, and the economic burden of uUTI. We examined the prevalence of suboptimal antibiotic prescribing and antibiotic resistance and its effects on healthcare resource use and costs.

Methods
This retrospective cohort study utilized electronic health record data from a large Mid-Atlantic US integrated delivery network database, collected July 2016–March 2020. Female patients aged ≥ 12 years with a uUTI, who received ≥ 1 oral antibiotic treatment within ± 5 days of index uUTI diagnosis, and had ≥ 1 urine culture with antimicrobial susceptibility test, were eligible for inclusion in the study. The study examined the proportion of antibiotics that were inappropriately or suboptimally prescribed among patients with confirmed uUTI, and total healthcare costs (all-cause and UTI-related) within 6 months after a uUTI, stratified by antibiotic susceptibility and/or inappropriate or suboptimal treatment. Patient outcomes were assessed after 1:1 propensity score matching of patients with antibiotic-susceptible versus not-susceptible isolates and then by other covariates (e.g., demographics and recent healthcare use). A similar propensity score calculation was used to analyze the effect of inappropriate/suboptimal treatment on health outcomes. Costs were adjusted to 2020 US dollars ($).

Results
Among 2565 patients with a uUTI included in the analysis, the most commonly prescribed antibiotics were nitrofurantoin (61%), trimethoprim-sulfamethoxazole (19%), and ciprofloxacin (15%). More than one-third of the sample (40.2%) had isolates that were not-susceptible to ≥ 1 antibiotic indicated for treating patients with uUTI. Two-thirds (66.6%) of study-eligible patients were prescribed appropriate treatment; 29.9% and 11.9% were prescribed suboptimal and/or inappropriate treatment, respectively. Inappropriate or suboptimally prescribed patients had greater all-cause and UTI-related costs compared with appropriately prescribed patients. Differences were most striking among patients with antibiotic not-susceptible isolates.

Conclusions
These findings highlight how the increasing prevalence of antibiotic resistance combined with suboptimal treatment of patients with uUTI increases the burden on healthcare systems. The finding underlines the need for improved prescribing accuracy by better understanding regional resistance rates and developing improved diagnostic tests.
A case of undifferentiated pleomorphic sarcoma in esophagus after multiple cancer treatments of surgery and chemoradiotherapy
Authors: Ebata Yuho , Sakaguchi Yoshihisa , Tsuda Yasuo , Nambara Sho , Kudou Kensuke , Kusumoto Eiji , Yoshida Rintaro , Kusumoto Tetsuya , Ikejiri Koji 
Published: November 2022

Abstract
Background
Undifferentiated pleomorphic sarcoma (UPS) in the esophagus is extremely rare. Therefore, there are few reports of UPS in the esophagus (UPSE). We present a case of UPSE after multiple cancer treatments.

Case presentation
A 73-year-old man with a history of cancer treatment, including distal gastrectomy, transverse colectomy, and chemoradiotherapy, was diagnosed with an elevated lesion such as a submucosal tumor in the lower esophagus by regular endoscopy. A boring biopsy was performed, and the specimen showed features of sarcoma. The patient underwent a partial esophagectomy without lymph node dissection. Histopathological findings confirmed an undifferentiated pleomorphic sarcoma. Adjuvant therapy was not administered, and the patient survived without recurrence 1 year after surgery.

Conclusions
Currently, complete resection is the only treatment option for UPSE. An optimal treatment strategy using chemotherapy or radiotherapy should be established.
Molar pregnancy unveiled by DNA profiling: a rare forensic case study
Authors: Pande Amulya , Daware Sudhakar , Thakare Vijay , Mahajan Vaishali , Dikshit Ankita , Dhawane Mitali 
Published: November 2022

Abstract
Background
Forensic DNA analysis is one of the most advanced tools in the criminal investigation. It is used successfully in solving offenses involving rape, paternity disputes, murder or attempt to murder, and dacoity as well as identification of mutilated body remains. DNA profiling is used to determine paternity in sexual offense cases where abortion takes place and the product of conception can be anywhere from 6 to 10 weeks of gestation to 8 months. In the present case, a tissue sample stated as a vesicular mole and blood samples of the mother and suspected father were submitted to the DNA division of our laboratory for paternity analysis.

Results
Genotyping results revealed a single allele at all the tested short tandem repeat (STR) loci. The allele obtained at each locus was common with the suspected father. Such type of genotype was very rare and not observed earlier; therefore, repeated analysis was done and the same genotype was obtained every time. DNA profiling revealed all the alleles in the vesicular mole to be of paternal origin only, devoid of any maternal alleles. After referring to books on gynecology, it was confirmed that the genotype obtained was of hydatidiform mole.

Conclusions
In this POCSO Act case, the product of conception (about 1.5 months old) was termed a vesicular mole, and blood samples of the mother and suspected father were sent for the DNA paternity test. STR profiling of the product of conception sample displayed no maternal tissue contamination and non-inheritance of maternal alleles, showing the case to be of molar pregnancy also called hydatidiform mole, a very rare phenomenon in the forensic scenario. After thorough analysis, the case was reported and it was the first of its kind to be reported in a forensic laboratory in Maharashtra, India.