bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of novel flavin-dependent monooxygenase from Strobilanthes Cusia reveals molecular basis of indoles’ biosynthetic logic
Authors: Liu Chang , Cheng Mengya , Ma Chao , Chen Junfeng , Tan Hexin 
Published: October 2023

Abstract
Background
Strobilanthes cusia (Nees) Kuntze is a traditional medical plant distributed widely in south China. The indole compounds that originated from the plant are responsible for its pharmacological activities. However, the reason why indole ingredients are accumulated in this herb and how it is biosynthesized has remained largely unknown.

Results
In this study, metabolic and transcriptional profiling measurement experiments of different S. cusia organs were carried out to understand the underlying molecular basis of indoles’ biosynthetic logic. A metabolic investigation demonstrated that the indoles are primarily accumulated mainly in aerial parts, particularly in leaves. RNA-seq was employed to reveal the organ specific accumulation of indoles in different S. cusia organs. Meanwhile, a flavin-dependent monooxygenase gene (ScFMO1) was found in S. cusia, and it has capacity to produce indoxyl from indole by the fermentation assay. Finally, we assessed the outcomes of transient expression experiment in tobacco and confirmed that ScFMO1 localizes in cytoplasm.

Conclusions
Our results suggest that ScFMO1 plays a key role in biosynthesis of indoles (Indigo, indirubin, indican, etc.), it will be useful for illuminating the molecular basis of the medicinal indoles’ biosynthesis and developing strategies for improving their yields.
Early outcomes of a triple-branched stent graft implantation in elderly patients with acute type a aortic dissection
Authors: Dong Yi , Wang Xuefei , Chen Liangwan , Wu Qingsong , Li Qianzhen 
Published: October 2023

Abstract
Purpose
Older patients with acute type A aortic dissection (ATAAD) have higher risk of mortality than that of younger patients when a total arch reconstruction (TAR) is required. Triple-branched stent graft (TBSG) implantation is a novel technique for TAR. However, early outcomes of a TBSG implantation in older patients have not been reported. This study aimed to evaluate the early outcomes of the TBSG technique in older patients with ATAAD.

Methods
From February 2015 to December 2020, 640 patients who simultaneously underwent an emergent open aortic surgery and TBSG implantation for ATAAD were enrolled in this study. They were categorized into the younger (age ≤ 70 years old, n = 573) and older groups (age > 70 years, n = 67). Clinical data of all patients were retrospectively reviewed.

Result
The mean ages of the patients in the younger and older groups were 45.3 ± 9.6 years old and 73.5 ± 3.0 years old, respectively. Preoperative characteristics were similar between the two groups, except for weight and incidence of moderate or greater aortic regurgitation, which were lower in the older group than those in the younger group. Surgical procedure and duration (i.e., duration for cardiopulmonary bypass, aortic cross-clamp, selected cerebral perfusion, and total circulation arrest) were comparable between the two groups (p > 0.05). Patients in the older group had higher incidence of dialysis for acute kidney injury and longer ICU stay compared with those in the younger group. However, the incidences of 30-day mortality (5.1% in younger group vs. 7.5% in older group, p = 0.407) and other major complications (i.e., neurological adverse events) were similar between the two groups.

Conclusion
TBSG implantation for ATAAD resulted in an acceptable mortality rate in patients above 70 years old, thus, it could be a feasible surgical procedure to perform in older patients with ATAAD when a TAR is required.
Elevated circulating PCSK9 level is associated with 28-day mortality in patients with sepsis: a prospective cohort study
Authors: Shu Yuanlu , Deng Ziwei , Deng Ye , Zhou Jianliang , Wang Jin , Duan Zhenxing , Jiang Tao , Zhao Xiang , Shi Zhihua , Qiu Chengfeng 
Published: October 2023

Abstract
Objectives
Pro-protein convertase subtilisin/kexin 9 (PCSK9) decreases the clearance of the pathogenic lipids, supporting the potential role of PCSK9 in the prognosis of sepsis.

Methods
In this prospective cohort study, patients with sepsis were consecutively recruited from 1 to 2020 to 30 September 2021 at the First People’s Hospital of Huaihua, China. All the eligible patients were categorized into low-PCSK9 and high-PCSK9 groups, based on their PCSK9 levels at admission. Time-dependent receiver operating characteristic curves and Cox proportional hazards regression were used to evaluate the association between PCSK9 level and 28-day mortality of sepsis.

Results
Of the 203 enrolled patients, 56 (27.59%) died during the 28-day follow-up. The PCSK9 level was positively related to the C-reactive protein level. The cut-off point of PCSK9 levels for 28-day mortality risk was 370 ng/ml. Through comparison between high-PCSK9 (> 370 ng/ml) with low-PCSK9 (≤ 370 ng/ml) groups, the adjusted HR for mortality was 2.56 (95% CI: 1.25–5.23, p = 0.01).

Conclusions
The 28-day mortality of sepsis increased significantly as the baseline circulating PCSK9 level exceeded 370 ng/ml, indicating circulating PCSK9 levels may be a potential biomarker to predict the prognosis of sepsis.
How to perform prespecified subgroup analyses when using propensity score methods in the case of imbalanced subgroups
Authors: Chatelet Florian , Verillaud Benjamin , Chevret Sylvie 
Published: October 2023

AbstractBackgroundLooking for treatment-by-subset interaction on a right-censored outcome based on observational data using propensity-score (PS) modeling is of interest. However, there are still issues regarding its implementation, notably when the subsets are very imbalanced in terms of prognostic features and treatment prevalence.MethodsWe conducted a simulation study to compare two main PS estimation strategies, performed either once on the whole sample (“across subset”) or in each subset separately (“within subsets”). Several PS models and estimands are also investigated. We then illustrated those approaches on the motivating example, namely, evaluating the benefits of facial nerve resection in patients with parotid cancer in contact with the nerve, according to pretreatment facial palsy.ResultsOur simulation study demonstrated that both strategies provide close results in terms of bias and variance of the estimated treatment effect, with a slight advantage for the “across subsets” strategy in very small samples, provided that interaction terms between the subset variable and other covariates influencing the choice of treatment are incorporated. PS matching without replacement resulted in biased estimates and should be avoided in the case of very imbalanced subsets.ConclusionsWhen assessing heterogeneity in the treatment effect in small samples, the “across subsets” strategy of PS estimation is preferred. Then, either a PS matching with replacement or a weighting method must be used to estimate the average treatment effect in the treated or in the overlap population. In contrast, PS matching without replacement should be avoided in this setting.
Impact of an INtervention to increase MOBility in older hospitalized medical patients (INTOMOB): Study protocol for a cluster randomized controlled trial
Authors: Mooser Blandine , Bergsma Dominique , Liechti Fabian D. , Baumgartner Christine , Gentizon Jenny , Méan Marie , Wertli Maria M. , Mancinetti Marco , Schmidt-Leuenberger Joachim , Aubert Carole E. 
Published: October 2023

Abstract
Background
Low mobility during an acute hospitalization is frequent and associated with adverse effects, including persistent functional decline, institutionalization and death. However, we lack effective interventions to improve mobility that are scalable in everyday practice. The INTOMOB trial – INtervention to increase MOBility in older hospitalized medical patients – will test the effect of a multilevel intervention to improve mobility of older hospitalized patients on functional mobility.

Methods
The INTOMOB multicenter superiority parallel cluster randomized controlled trial will enroll in total 274 patients in Swiss hospitals. Community-dwelling adults aged ≥ 60 years, admitted to a general internal medicine ward with an anticipated length of hospital stay of ≥ 3 days, will be eligible for participation. Unit of randomization will be the wards. A multilevel mobility intervention will be compared to standard of care and target the patients (information and exercise booklets, mobility diary, iPad with exercise videos), healthcare professionals (e-learning, oral presentation, mobility checklist), and environment (posters and pictures on the wards). The primary outcome will be life-space level, measured by the University of Alabama at Birmingham Study of Aging Life-Space Assessment (LSA), at 30 days after enrollment. The LSA is a measure of functional mobility, i.e., how far participants move from bedroom to outside town. Secondary outcomes include, among others, LSA at 180 days, mobility and falls during hospitalization, muscle strength at discharge, and falls, emergency room visits, readmissions, and death within 180 days.

Discussion
This study has the potential to improve outcomes of older hospitalized patients through an intervention that should be scalable in clinical practice because it fosters patient empowerment and does not require additional resources. The tools provided to the patients can help them implement better mobility practices after discharge, which can contribute to better functional outcomes. The choice of a functional patient-reported outcome measure as primary outcome (rather than a “simple” objective mobility measure) reinforces the patient-centeredness of the study.

Trial registration
clinicaltrials.gov (NCT05639231, released on December 19 2022); Swiss National Clinical Trial Portal (SNCTP000005259, released on November 28 2022).
Association between chronic pain and acute coronary syndrome in the older population: a nationwide population-based cohort study
Authors: Liu Yu-Chang , Ho Chung-Han , Chen Yi-Chen , Hsu Chien-Chin , Lin Hung-Jung , Wang Chia-Ti , Huang Chien-Cheng 
Published: October 2023

Abstract
Background
Chronic pain (CP) may increase the risk of acute coronary syndrome (ACS); however, this issue in the older population remains unclear. Therefore, this study was conducted to clarify it.

Methods
We used the Taiwan National Health Insurance Research Database to identify older patients with CP between 2001 and 2005 as the study cohort. Comparison cohort was the older patients without CP by matching age, sex, and index date at 1:1 ratio with the study cohort in the same period. We also included common underlying comorbidities in the analyses. The risk of ACS was compared between the two cohorts by following up until 2015.

Results
A total of 17241 older patients with CP and 17241 older patients without CP were included in this study. In both cohorts, the mean age (± standard deviation) and female percentage were 73.5 (± 5.7) years and 55.4%, respectively. Spinal disorders (31.9%) and osteoarthritis (27.0%) were the most common causes of CP. Older patients with CP had an increased risk for ACS compared to those without CP after adjusting for all underlying comorbidities (adjusted sub-distribution hazard ratio [sHR] 1.18; 95% confidence interval: 1.07–1.30). The increasement of risk of ACS was more when the follow-up period was longer (adjusted sHR of < 3 years: 1.8 vs. <2 years: 1.75 vs. <1 year: 1.55).

Conclusions
CP was associated with an increased risk of ACS in the older population, and the association was more prominent when the follow-up period was longer. Early detection and intervention for CP are suggested in this population.
Psychometric evaluation of the Protection Motivation Theory scale in assessing fall protection motivation among older adults to reduce fall risk
Authors: Ong Mei Fong , Soh Kim Lam , Saimon Rosalia , Tiong Ing Khieng , Saidi Hasni Idayu , Mortell Manfred 
Published: October 2023

Abstract
Background
Protection Motivation Theory could be another potential and good framework that addresses essential elements in a behavioural change leading to positive fall protective behaviours. The positive behavioural change could reduce the risk of falls and improve the quality of life of the older community. The study aims to evaluate the reliability and validity of the culturally adapted Protection Motivation Theory scale for older adults' fall protection motivation or protective behaviours to reduce fall risk.

Methods
A cross-sectional study was conducted to establish a psychometric instrument validation. A total of 389 participants aged 55 years and above were included. The study was conducted in Sarawak, Malaysia, from November 2021 to January 2022 in two phases, translation of the PMT Scale, cross-cultural adaptation, face validation and pre-testing of the PMT Scale. The participants were selected using multistage random sampling in a primary healthcare clinic. Data entry and statistical analysis were performed using IBM SPSS version 26 for exploratory factor analysis and SmartPLS version 3.3.7 for confirmatory factor analysis using partial least square structural equation modelling.

Results
The Kaiser–Meyer–Olkin value was 0.760, Bartlett's sphericity test was significant and the total variance explained was 61%. It identified 31 items within eight dimensions of the Protection Motivation Theory scale. The Higher Order Constructs' measurement model indicates that the convergent and discriminant validity were established (Cronbach's alpha and composite reliability: ≥ 0.740; average variance extracted: 0.619 to 0.935 and Henseler's Heterotrait-Monotrait criterion for all constructs' discriminant validity: < 0.9). Test–retest for the intraclass correlation coefficient was 0.745. The model's coefficient of determination demonstrated R2 = 0.375.

Conclusion
Overall, the Protection Motivation Theory Scale has established its reliability and validity for assisting older adults in the community. The Protection Motivation Theory Scale could be used in fall prevention interventions by promoting fall protective behaviours to reduce fall risk among community-dwelling older adults. The scale could assist healthcare providers in assessing the intention of older adults to use fall protective behaviours to reduce fall risk and serve as an alternative reference in developing fall prevention education in a fall prevention strategy.
Assessing the COVID-19 vaccination program during the Omicron variant (B.1.1.529) epidemic in early 2022, Tokyo
Authors: Kayano Taishi , Nishiura Hiroshi 
Published: October 2023

AbstractBackgroundMany countries, including high-income nations, struggled to control epidemic waves caused by the Omicron variant (B.1.1.529), which had an antigenically distinct evolution. Evaluating the direct and indirect effects of vaccination during the Omicron waves is essential to assess virus control policies. The present study assessed the population impacts of a vaccination program during the sixth wave caused by BA.1 and BA.2 from January to May 2022, in Tokyo.MethodsWe analyzed the primary series and booster vaccination coverages and the confirmed cases stratified by vaccination history. We estimated the number of COVID-19 cases that were directly and indirectly prevented by vaccination. To estimate the direct impact, we used a statistical model that compared risks between unvaccinated and vaccinated individuals. A transmission model employing the renewal process was devised to quantify the total effect, given as the sum of the direct and indirect effects.ResultsAssuming that the reporting coverage of cases was 25%, mass vaccination programs, including primary and booster immunizations, directly averted 640,000 COVID-19 cases (95% confidence interval: 624–655). Furthermore, these programs directly and indirectly prevented 8.5 million infections (95% confidence interval: 8.4–8.6). Hypothetical scenarios indicated that we could have expected a 19% or 7% relative reduction in the number of infections, respectively, compared with the observed number of infections, if the booster coverage had been equivalent to that of the second dose or if coverage among people aged 10–49 years had been 10% higher. If the third dose coverage was smaller and comparable to that of the fourth dose, the total number of infections would have increased by 52% compared with the observed number of infections.ConclusionsThe population benefit of vaccination via direct and indirect effects was substantial, with an estimated 65% reduction in the number of SARS-CoV-2 infections compared with counterfactual (without vaccination) in Tokyo during the sixth wave caused by BA.1 and BA.2.
A case of acute kidney injury due to native kidney BK polyomavirus-associated nephropathy in a human T-lymphotropic virus type 1 carrier
Authors: Takae Keita , Ueno Yuki , Shojima Masumi , Nagae Hiroshi , Nakano Takako , Takata Shohei , Katafuchi Ritsuko , Masutani Kosuke , Nakano Toshiaki , Kuroki Yusuke 
Published: October 2023

Abstract
Background
BK polyomavirus-associated nephropathy (BKPyVAN) has become a major cause of kidney dysfunction and graft loss in kidney transplant recipients. On rare occasion, polyomavirus has also been known to affect native kidneys of immunocompromised individuals. Only a small number of opportunistic infections have been reported in the carrier phase of human T-lymphotropic virus type 1 (HTLV-1). This is the first reported case of BKPyVAN in native kidneys of an HTLV-1 carrier.

Case presentation
A 61-year-old man was referred to our hospital from a primary care physician for work-up and treatment of pneumonia. He was diagnosed with Pneumocystis pneumonia and identified as a HTLV-1 carrier who had not yet developed adult T-cell leukemia (ATL). The pneumonia was successfully treated with sulfamethoxazole-trimethoprim. He had never been diagnosed with any kind of kidney dysfunction. Laboratory investigations showed a serum creatinine of 5.3 mg/dL, and urinary sediment showed cells with nuclear enlargement and inclusion bodies suggesting viral infection. The urinary Papanicolaou stain showed inclusions in swollen, ground-glass nuclei, typical of “decoy cells”. Renal biopsy showed degeneration of tubules with epithelial enlargement, vacuolar degeneration, nuclear inclusion bodies, and detachment from the tubular basement membrane. Tubular nuclei showed positive staining positive for simian virus 40 large-T antigen. Polymerase chain reaction tests for BK polyomavirus DNA of both urine and plasma were positive. These findings confirmed a diagnosis of BKPyVAN. Intravenous immunoglobulin therapy did not improve renal function, necessitating maintenance hemodialysis therapy.

Conclusions
BKPyVAN should be considered when acute kidney injury occurs with opportunistic infection. HTLV-1 carriers can develop opportunistic infections even before the onset of ATL.
Changes in electrophysiological findings of spinal muscular atrophy type I after the administration of nusinersen and onasemnogene abeparvovec: two case reports
Authors: Mizuno Tomoko , Kanouchi Tadashi , Tamura Yumie , Hirata Ko , Emoto Runa , Suzuki Tomonori , Kashimada Kenichi , Morio Tomohiro 
Published: October 2023

Abstract
Background
Recently, there have been significant advances in the treatment of spinal muscular atrophy (SMA). Although clinical improvement in patients with SMA after the treatment has been reported, changes in electrophysiological findings, especially needle electromyography (EMG), have rarely been reported. Herein, we report the posttreatment changes in EMG and nerve conduction study findings over time in two patients with SMA type I.

Case presentation
Patient 1: A 2.5-year-old girl was diagnosed with SMA type I at 1 month of age. She received nusinersen four times and onasemnogene abeparvovec (OA) was administered at 6 months of age. The compound muscle action potential (CMAP) amplitudes of the median and tibial nerves increased over time. The needle EMG after the treatment showed high-amplitude motor unit potentials (MUPs) suggestive of reinnervation during voluntary contraction, which were not seen before the treatment. However, fibrillation potentials at rest were still seen after the treatment. Patient 2: A 2-year-old girl was diagnosed with SMA type I at 6 months of age. She had received nusinersen two times and OA was administered at 7 months of age. The CMAP amplitudes and the MUPs presented similar changes as presented in Case 1.

Conclusion
This is the first report on the changes in needle EMG findings after treatment in patients with SMA type I. These findings suggested that peripheral nerve reinnervation occurred after the treatment, although active denervation was still present. The accumulation of these findings will be important for evaluating the effectiveness of treatment for SMA in the future.
Survival outcomes including salvage therapy of adult head and neck para-meningeal rhabdomyosarcoma: a multicenter retrospective study from Japan
Authors: Tsuchihashi Kenji , Ito Mamoru , Arita Shuji , Kusaba Hitoshi , Kusano Wataru , Matsumura Takashi , Kitazono Takafumi , Ueno Shohei , Taguchi Ryosuke , Yoshihiro Tomoyasu , Doi Yasuhiro , Arimizu Kohei , Ohmura Hirofumi , Kajitani Tatsuhiro , Nio Kenta , Nakano Michitaka , Oshima Kotoe , Tamura Shingo , Shirakawa Tsuyoshi , Shimokawa Hozumi , Uchino Keita , Hanamura Fumiyasu , Okumura Yuta , Komoda Masato , Isobe Taichi , Ariyama Hiroshi , Esaki Taito , Hashimoto Kazuki , Komune Noritaka , Matsuo Mioko , Matsumoto Keiji , Asai Kaori , Yoshitake Tadamasa , Yamamoto Hidetaka , Oda Yoshinao , Akashi Koichi , Baba Eishi 
Published: October 2023

Abstract
Background
Rhabdomyosarcoma is the most common soft tissue sarcoma in children, but rare in adults. Para-meningeal rhabdomyosarcoma in head and neck (PM-HNRMS) is less applicable for surgery due to the anatomic reason. PM-HNRMS has a poor prognosis in children. However, its clinical outcomes remain unclear in adults due to the rarity. Further, there is almost no detailed data about salvage therapy.

Methods
We retrospectively examined the adult patients with PM-HNRMS treated at institutions belonging to the Kyushu Medical Oncology Group from 2009 to 2022. We evaluated the overall survival (OS) and progression-free survival (PFS) of the patients who received a first-line therapy. We also reviewed the clinical outcomes of patients who progressed against a first-line therapy and received salvage therapy.

Results
Total 11 patients of PM-HNRMS received a first-line therapy. The characteristics were as follows: median age: 38 years (range 25 – 63 years), histology (alveolar/spindle): 10/1, and risk group (intermediate/high): 7/4. As a first-line therapy, VAC and ARST0431-based regimen was performed in 10 and 1 patients, respectively. During a first-line therapy, definitive radiation for all lesions were performed in seven patients. The median PFS was 14.2 months (95%CI: 6.0 – 25.8 months): 17.1 months (95%CI: 6.0 – not reached (NR)) for patients with stage I-III and 8.5 months (95%CI: 5.2 – 25.8 months) for patients with stage IV. The 1-year and 3-year PFS rates were 54.5% and 11.3% for all patients. Median OS in all patients was 40.8 months (95%CI: 12.1 months–NR): 40.8 months (95%CI: 12.1 – NR) for patients with stage I-III and NR for patients with stage IV. The 5-year OS rate was 48.5% for all patients. Among seven patients who received salvage therapy, three are still alive, two of whom remain disease-free for over 4 years after completion of the last therapy. Those two patients received multi-modal therapy including local therapy for all detected lesions.

Conclusion
The cure rate of adult PM-HNRMS is low in spite of a first-line therapy in this study. Salvage therapy might prolong the survival in patients who received the multi-modal therapy including local therapy for all detected lesions.