bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of acupuncture for hand osteoarthritis: study protocol for a multi-center, randomized, sham-controlled clinical trial
Authors: Wang Weiming , Shi Hangyu , Liu Yan , Sun Yuanjie , Chen Yu , Liu Zhishun 
Published: February 2023

Abstract
Background
Hand osteoarthritis (OA) is a prevalent disorder in the general population. Patients with hand OA often report symptoms of pain, stiffness, and functional limitations, which cause clinical burden and impact on quality of daily life. However, the efficacy of current therapies for hand OA is limited. Other therapies with better effects and less adverse events are in urgent need. Acupuncture is well known for analgesia and has been proved effective in treating basal thumb joint arthritis. This study aims to clarify the efficacy and safety of acupuncture treatment for clinical symptomatic improvement of hand OA.

Methods
This will be a sham-controlled, randomized, multi-center clinical trial. A total of 340 participants will be recruited and randomly allocated to either traditional acupuncture group or sham acupuncture group. All participants will receive 12 treatment sessions over 4 weeks and 2 follow-up assessments in the following 3 months at week 8 and week 16. The primary outcome will be the proportion of responders at week 5. Secondary outcomes will include visual analog scale, Australian Canadian Osteoarthritis Hand Index, Functional Index for hand OA, the number of symptomatic joints, hand grip strength and pinch strength, global assessment, the World Health Organization Quality of Life abbreviated version and expectations. Safety will be evaluated during the whole process of the trial. All outcomes will be analyzed following the intention-to-treat principle.

Discussion
This prospective trial will provide high-quality evidence on evaluating the efficacy and safety of acupuncture treatment for hand OA. Results of this trial might contribute in offering a new option to clinical recommendations.
Trial registration ClinicalTrials.gov Identifier: NCT05267093. Registered 23 February 2022.
Combined with UPLC-Triple-TOF/MS-based plasma lipidomics and molecular pharmacology reveals the mechanisms of schisandrin against Alzheimer’s disease
Authors: Zhao Tian-tian , Zhang Ying , Zhang Cheng-qin , Chang Ya-fei , Cui Mei-rong , Sun Yue , Hao Wen-qian , Yan Yu-meng , Gu Shuo , Xie Yao , Wei Bin-bin 
Published: February 2023

Abstract
Background
Alzheimer’s disease (AD), a type of neurodegeneration disease, is characterized by Aβ deposition and tangles of nerve fibers. Schisandrin is one of the main components of Fructus Schisandrae Chinensis. Researches showed that schisandrin can improve the cognitive impairment and memory of AD mice, but the specific mechanism has not been fully elucidated.

Purpose
The purpose of this study is to investigate the possible mechanism of schisandrin in improving AD pathology.

Methods
The Morris water maze test was executed to detect spatial learning and memory. Ultra performance liquid chromatography-Triple time of flight mass spectrometry (UPLC-Triple-TOF/MS)-based plasma lipidomics was used to study the changes of plasma lipids. Moreover, we measured the levels of protein and mRNA expression of APOE and ABCA1 in the rat brains and in BV2 microglia.

Results
Our study found that schisandrin could improve learning and memory, and reduce Aβ deposition in AD rats. Furthermore, we found that schisandrin can improve plasma lipid metabolism disorders. Therefore, we hypothesized schisandrin might act via LXR and the docking results showed that schisandrin interacts with LXRβ. Further, we found schisandrin increased the protein and mRNA expression of LXR target genes APOE and ABCA1 in the brain of AD rats and in BV2 microglia.

Conclusion
Our study reveals the neuroprotective effect and mechanism of schisandrin improves AD pathology by activating LXR to produce APOE and ABCA1.
The distribution of neuroligin4, an autism-related postsynaptic molecule, in the human brain
Authors: Toya Akie , Fukada Masahide , Aoki Eiko , Matsuki Tohru , Ueda Masashi , Eda Shima , Hashizume Yoshio , Iio Akio , Masaki Shigeo , Nakayama Atsuo 
Published: February 2023

AbstractNLGN4X was identified as a single causative gene of rare familial nonsyndromic autism for the first time. It encodes the postsynaptic membrane protein Neuroligin4 (NLGN4), the functions and roles of which, however, are not fully understood due to the lack of a closely homologous gene in rodents. It has been confirmed only recently that human NLGN4 is abundantly expressed in the cerebral cortex and is localized mainly to excitatory synapses. However, the detailed histological distribution of NLGN4, which may have important implications regarding the relationships between NLGN4 and autistic phenotypes, has not been clarified. In this study, we raised specific monoclonal and polyclonal antibodies against NLGN4 and examined the distribution of NLGN4 in developing and developed human brains by immunohistochemistry. We found that, in the brain, NLGN4 is expressed almost exclusively in neurons, in which it has a widespread cytoplasmic pattern of distribution. Among various types of neurons with NLGN4 expression, we identified consistently high expression of NLGN4 in hypothalamic oxytocin (OXT)/vasopressin (AVP)-producing cells. Quantitative analyses revealed that the majority of OXT/AVP-producing neurons expressed NLGN4. NLGN4 signals in other large neurons, such as pyramidal cells in the cerebral cortex and hippocampus as well as neurons in the locus coeruleus and the raphe nucleus, were also remarkable, clearly contrasting with no or scarce signals in Purkinje cells. These data suggest that NLGN4 functions in systems involved in intellectual abilities, social abilities, and sleep and wakefulness, impairments of which are commonly seen in autism.
Effectiveness of an evidence-based care pathway to improve mobility and participation in older patients with vertigo and balance disorders in primary care (MobilE-PHY2): study protocol for a multicentre cluster-randomised controlled trial
Authors: Horstmannshoff Caren , Skudlik Stefanie , Petermann Jenny , Kiesel Theresia , Döringer Tobias , Crispin Alexander , Hermsdörfer Joachim , Köberlein-Neu Juliane , Jahn Klaus , Schädler Stefan , Bauer Petra , Voigt Karen , Müller Martin 
Published: February 2023

Abstract
Background
Vertigo, dizziness or balance disorders (VDB) are common leading symptoms in older people, which can have a negative impact on their mobility and participation in daily live, yet, diagnosis is challenging and specific treatment is often insufficient. An evidence-based, multidisciplinary care pathway (CPW) in primary care was developed and pilot tested in a previous study. The aim of the present study is to evaluate the effectiveness and safety of the CPW in terms of improving mobility and participation in community-dwelling older people with VDB in primary care.

Methods
For this multicentre cluster randomised controlled clinic trial, general practitioners (GP) will be recruited in two regions of Germany. A total of 120 patients over 60 years old with VDB will be included. The intervention is an algorithmized CPW. GPs receive a checklist for standardise clinical decision making regarding diagnostic screening and treatment of VDB. Physiotherapists (PT) receive a decision tree for evidence-based physiotherapeutic clinical reasoning and treatment of VDB. Implementation strategies comprises educational trainings as well as a workshop to give a platform for exchange for the GPs and PTs, an information meeting and a pocket card for home care nurses and informal caregivers and telephone peer counselling to give all participants the capability, opportunity and the motivation to apply the intervention. In order to ensure an optimised usual care in the control group, GPs get an information meeting addressing the national guideline. The primary outcome is the impact of VDB on participation and mobility of patients after 6 month follow-up, assessed using the Dizziness Handicap Inventory (DHI) questionnaire. Secondary outcomes are physical activity, static and dynamic balance, falls and fear of falling as well as quality of life. We will also evaluate safety and health economic aspects of the intervention. Behavioural changes of the participants as well as barriers, facilitating factors and mechanisms of impact of the implementation will be investigated with a comprehensive process evaluation in a mixed-methods design.

Discussion
With our results, we aim to improve evidence-based health care of community-dwelling older people with VDB in primary care.

Trial registration
DRKS, DRKS00028524 retrospectively registered on March 24, 2022.
The COMFORT trial: a randomised control trial comparing group-based COMpassion-FOcussed therapy and breathing pattern ReTraining with treatment as usual on the psychological functioning of patients diagnosed with cancer recurrence during COVID
Authors: Lynch Sinead , Lowry Damien , Finnerty Clodagh , O’Meara Yvonne , Brennan Donal 
Published: February 2023

Abstract
Background
A cancer diagnosis is a known precipitant of psychological distress, with fear of recurrence being a well-documented distressing consequence of cancer. Cancer recurrence often results in an additional psychological burden, which may exacerbate as a result of the COVID-19 pandemic.

Methods
This is a single-centre, prospective, randomised controlled trial. Patients identified as having experienced cancer recurrence since March 2020 (the onset of the COVID-19 pandemic in Ireland) will be screened for participation. Eligible, consenting candidates who score 4 or higher on the Distress Thermometer will be enrolled in the study. Participants will be randomly allocated to receive either a 6-week, group-based, online, compassion-focussed therapy and breathing pattern retraining intervention or the control arm. Those in the control arm will all be offered the group intervention after the 18-week study period. The primary outcome is the Distress Thermometer score at 18 weeks post-baseline though secondary outcomes will include measures of mood, traumatic distress and mental adjustment to cancer.

Discussion
To our knowledge, this protocol describes the first RCT which directly examines the effect of a group-based psychological intervention on Irish patients experiencing cancer recurrence in the context of COVID-19. The outcome of this trial is likely to be twofold: It will determine if the psychological intervention achieves its primary objective of distress amelioration 3 months post-intervention and to establish the feasibility of delivering this intervention in a virtual format.

Trial registration
ClinicalTrials.gov NCT05518591. Registered on 25 August 2022. All items from the World Health Organization Trial Registration Data set have been included.
Multidimensional individualized nutritional therapy for individuals with severe chronic obstructive pulmonary disease: study protocol for a registry-based randomized controlled trial
Authors: Hegelund Maria H. , Ritz Christian , Nielsen Thyge L. , Olsen Mette F. , Søborg Christian , Braagaard Lone , Mølgaard Christian , Krogh-Madsen Rikke , Lindegaard Birgitte , Faurholt-Jepsen Daniel 
Published: February 2023

Abstract

Background
Individuals with severe chronic obstructive pulmonary disease (COPD) are often at risk of undernutrition with low health-related quality of life (HRQoL). Undernutrition can worsen COPD and other comorbidities, be an independent predictor of morbidity and functional decline resulting in increased healthcare consumption and increased risk of death. Especially exacerbations and acute infections result in unintentional weight loss. The aim is to investigate the effect of an individualized nutritional intervention among individuals with severe COPD.

Methods
An open-label randomized controlled trial with two parallel groups. Participants are recruited from the pulmonary outpatient clinic at the Department of Pulmonary and Infectious Diseases, Copenhagen University Hospital, North Zealand, Denmark, and randomly allocated to either the intervention (intervention + standard of care) or control group (standard of care). The intervention has a duration of 3 months and combines individual nutritional care with adherence support and practical tools. It contains 4 elements including an individual nutritional plan, regular contacts, adherence support, and weight diary. The primary outcome is a difference in HRQoL (EQ-5D-5L) between the intervention and control group 3 months after baseline. Difference in functional capacity (grip strength, 30-s stand chair test, and physical activity), disease-specific quality of life (COPD Assessment Test), anxiety and depression (Hospital Anxiety and Depression Scale), nutritional parameters (energy and protein intake), anthropometry (weight, body mass index, waist, hip, and upper arm circumference), body composition (total fat-free and fat mass and indices), and prognosis (exacerbations, oxygen therapy, hospital contacts, and mortality) 3 months after baseline will be included as secondary outcomes. Data will be collected through home visits at baseline and 1 and 3 months after baseline.

Discussion
Currently, nutritional care is a neglected area of outpatient care among individuals with severe COPD. If this patient-centered approach can demonstrate a positive impact on HRQoL, mortality, and hospital contacts, it should be recommended as part of end-of-life care for individuals with severe COPD.

Trial registration
ClinicalTrials.gov NCT04873856
. Registered on May 3, 2021.
Production of 1,2-propanediol from glycerol in Klebsiella pneumoniae GEM167 with flux enhancement of the oxidative pathway
Authors: Jo Min-Ho , Ju Jung-Hyun , Heo Sun-Yeon , Cho Jaehoon , Jeong Ki Jun , Kim Min-Soo , Kim Chul-Ho , Oh Baek-Rock 
Published: February 2023

Abstract
Background
To support the sustainability of biodiesel production, by-products, such as crude glycerol, should be converted into high-value chemical products. 1,2-propanediol (1,2-PDO) has been widely used as a building block in the chemical and pharmaceutical industries. Recently, the microbial bioconversion of lactic acid into 1,2-PDO is attracting attention to overcome limitations of previous biosynthetic pathways for production of 1,2-PDO. In this study, we examined the effect of genetic engineering, metabolic engineering, and control of bioprocess factors on the production of 1,2-PDO from lactic acid by K. pneumoniae GEM167 with flux enhancement of the oxidative pathway, using glycerol as carbon source.

Results
We developed K. pneumoniae GEM167ΔadhE/pBR-1,2PDO, a novel bacterial strain that has blockage of ethanol biosynthesis and biosynthesized 1,2-PDO from lactic acid when glycerol is carbon source. Increasing the agitation speed from 200 to 400 rpm not only increased 1,2-PDO production by 2.24-fold to 731.0 ± 24.7 mg/L at 48 h but also increased the amount of a by-product, 2,3-butanediol. We attempted to inhibit 2,3-butanediol biosynthesis using the approaches of pH control and metabolic engineering. Control of pH at 7.0 successfully increased 1,2-PDO production (1016.5 ± 37.3 mg/L at 48 h), but the metabolic engineering approach was not successful. The plasmid in this strain maintained 100% stability for 72 h.

Conclusions
This study is the first to report the biosynthesis of 1,2-PDO from lactic acid in K. pneumoniae when glycerol was carbon source. The 1,2-PDO production was enhanced by blocking the synthesis of 2,3-butanediol through pH control. Our results indicate that K. pneumoniae GEM167 has potential for the production of additional valuable chemical products from metabolites produced through oxidative pathways.
A comprehensive survey of permethrin resistance in human head louse populations from northwest Iran: ex vivo and molecular monitoring of knockdown resistance alleles
Authors: Ghavami Mohammad Bagher , Panahi Sanaz , Nabati Seyede Maede , Ghanbari Maryam , Taghiloo Behrooz 
Published: February 2023

Abstract
Background
Head louse infestation is an important public health problem, and expanding resistance to permethrin is a major challenge to its control. The mapping and detection of pyrethroid resistance are essential to the development of appropriate treatments and ensure the effectiveness of current measures. The aim of this study was to present the phenotypic and genotypic basis of permethrin resistance and identify knockdown resistance (kdr) mutations in head louse populations in northwestern Iran.

Methods
Adult head lice were collected from 1059 infested girls in Ardebil, East Azerbaijan, West Azerbaijan and Zanjan Provinces, northwestern Iran. The toxicity of permethrin and the possible synergistic effect of piperonyl butoxide (PBO) on this toxicity were assessed using bioassays. Fragments of voltage-sensitive sodium channels (vssc) and cytochrome b (cytb) genes were amplified and analyzed for the detection of knockdown resistance (kdr) mutations and mitochondrial groups. Moreover, genotypes of the two hot spot regions of the vssc gene were determined by melting curve analysis of amplicons.

Results
A total of 1450 adult head lice were collected during 2016–2021. Live lice were exposed to a dose of 1% permethrin for 12 h, and the median lethal time (LT50) and time to achieve 90% mortality (LT90) were determined to be 6 and 14.8 h, respectively. Topical application of 2 and 16 ng permethrin per louse resulted in 25% and 42.11% mortality, respectively. Pre-exposure of samples to 3% piperonyl butoxide had no synergistic effect on the effects of permethrin. Analysis of the 774-bp vssc gene fragment showed the presence of the M815I, T917I and L920F mutations, wild-type and T917I mutation, in 91.6%, 4.2% and 4.2% of samples, respectively. Investigation of the mitochondrial cytb gene demonstrated the predominance of clade B. The frequency of domain II segment 4 (S4)-S5 kdr genotypes in mitochondrial groups was identical, and heterozygotes were present in 93.5% of samples. A significant difference was detected in the frequency of domain IIS1-S3 kdr genotypes, and the frequency of resistant alleles and heterozygotes was higher in clade B than in clade A.

Conclusions
The presence of kdr mutations in the vssc gene and the non-synergist effect of PBO indicate that pyrethroid target site insensitivity is the main resistance mechanism. This phenomenon and the high frequency of resistant alleles necessitate that new pediculosis management programs be developed. Further studies need to be conducted to identify all factors contributing this resistance and to develop alternative pediculicides.

Graphical Abstract
A novel inflammatory biomarker, high-sensitivity C-reactive protein-to-albumin ratio, is associated with 5-year outcomes in patients with type 2 diabetes who undergo percutaneous coronary intervention
Authors: Li Jiawen , Zhu Pei , Li Yulong , Yan Kailun , Tang Xiaofang , Xu Jingjing , Yang Weixian , Qiao Shubin , Yang Yuejin , Gao Runlin , Xu Bo , Yuan Jinqing , Zhao Xueyan 
Published: February 2023

Abstract
Background
Patients with coronary artery disease (CAD) combined with diabetes have a higher risk of cardiovascular events, and high-sensitivity C-reactive protein (hs-CRP)-to-albumin ratio (CAR) is a novel inflammatory biomarker. However, whether the CAR can identify high-risk patients with CAD and type 2 diabetes (T2DM) remains unclear.

Methods
The present study was based on a prospective and observational cohort with 10,724 individuals who undergo percutaneous coronary intervention (PCI) in Fu Wai Hospital throughout the year 2013 consecutively enrolled. The primary endpoint was all-cause mortality. The secondary endpoint was cardiac mortality. CAR was calculated with the formula: hs-CRP (mg/L)/albumin (g/L). According to the optimal cut-off value of CAR for all-cause mortality, patients were divided into higher CAR (CAR-H) and lower CAR (CAR-L) groups.

Results
A total of 2755 patients with T2DM who underwent PCI and received dual antiplatelet therapy were finally enrolled. During a follow-up of 5 years (interquartile range: 5.0–5.1 years), 126 (4.6%) all-cause mortalities and 74 (2.7%) cardiac mortalities were recorded. In the multivariable Cox model, CAR-H was associated with a higher risk of all-cause mortality (hazard ratio [HR]: 1.634, 95% confidence interval [CI] 1.121–2.380, p = 0.011) and cardiac mortality (HR: 1.733, 95% CI 1.059–2.835, p = 0.029) compared with CAR-L. When comparing the predictive value, CAR was superior to hs-CRP for all-cause mortality (area under the curve [AUC] 0.588 vs. 0.580, p = 0.002) and cardiac mortality (AUC 0.602 vs. 0.593, p = 0.004).

Conclusion
In this real-world cohort study, a higher level of CAR was associated with worse 5-year outcomes among diabetic patients with PCI.
A molecular epidemiological study on Escherichia coli in young chicks with colibacillosis identified two possible outbreaks across farms
Authors: Kravik Inger Helene , Kaspersen Håkon , Sjurseth Siri Kulberg , Dean Katharine Rose , David Bruce , Aspholm Marina , Sekse Camilla 
Published: February 2023

AbstractAvian pathogenic Escherichia coli (APEC) is the cause of colibacillosis outbreaks in young poultry chicks, resulting in acute to peracute death. The high morbidity and mortality caused by colibacillosis results in poor animal welfare, reduced sustainability and economical loss worldwide. To advance the understanding of the molecular epidemiology, genomic relatedness and virulence traits of APEC, we performed systematic sampling from 45 confirmed colibacillosis broiler flocks with high first week mortality (FWM) during 2018–2021. From these flocks, 219 APEC isolates were whole genome sequenced (WGS) and bioinformatic analyses were performed. The bioinformatic analyses included sequence typing (ST), serotyping, detection of virulence-associated genes (VAGs) and phylogenetic analysis. Our results showed a high prevalence of ST23, ST429 and ST95 among APEC isolates from Norwegian broiler flocks, and identified ST23, ST429, ST117 and ST371 to cause disease more often alone, compared to ST95, ST69 and ST10. Phylogenetic analyses, together with associated metadata, identified two distinct outbreaks of colibacillosis across farms caused by ST429 and ST23 and gave insight into expected SNP distances within and between flocks identified with the same ST. Further, our results highlighted the need for combining two typing methods, such as serotyping and sequence typing, to better discriminate strains of APEC. Ultimately, systematic sampling of APEC from multiple birds in a flock, together with WGS as a diagnostic tool is important to identify the disease-causing APEC within a flock and to detect outbreaks of colibacillosis across farms.
A Gronwall inequality and its applications to the Cauchy-type problem under ψ-Hilfer proportional fractional operators
Authors: Sudsutad Weerawat , Thaiprayoon Chatthai , Khaminsou Bounmy , Alzabut Jehad , Kongson Jutarat 
Published: February 2023

AbstractIn this paper, we propose a generalized Gronwall inequality in the context of theψ-Hilfer proportional fractional derivative. Using Picard’s successive approximation and the definition of Mittag–Leffler functions, we construct the representation formula of the solution for theψ-Hilfer proportional fractional differential equation with constant coefficient in the form of the Mittag–Leffler kernel. The uniqueness result is proved by using Banach’s fixed-point theorem with some properties of the Mittag–Leffler kernel. Additionally, Ulam–Hyers–Mittag–Leffler stability results are analyzed. Finally, numerical examples are provided to demonstrate the theory’s application.